June 29, 2025 • 35 mins
This is Episode 20B: Anal Cancer Part 4: Guidelines, Toxicity, Follow-Up & Future Directions. Over the last three episodes, we've built a comprehensive understanding of anal cancer, from its foundational anatomy and staging, to the landmark trials that established definitive chemoradiation, and the technical details of modern IMRT planning. We've learned the 'what,' 'why,' and 'how' of our standard of care. In this final episode of our anal cancer series, we bring everything together. We will synthesize the key recommendations from the landmark 2025 ASTRO Clinical Practice Guideline, which now serves as our primary evidence-based roadmap. We'll then discuss practical strategies for managing acute and late toxicities, outline the evidence-based approach to post-treatment surveillance, and look ahead at the future directions of anal cancer research.
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Episode Transcript
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(00:00):
Welcome everyone to the Radon Smart Review GI Cancer series.
We've really journeyed through the the intricate landscape of
anal cancer in our previous sessions, building quite a
robust foundation. We've explored everything from
the, you know, the fundamental anatomy and epidemiology right
through to pathology work up staging.
All the foundational pieces. Exactly.
(00:22):
And then we moved into those landmark trials, the ones that
really established definitive chemeradiation as our well, our
standard of care. We've even got into the nitty
gritty of IMRT planning. The technical side.
Yeah. So today this is part 4 and it's
crucial. Our mission is to synthesize all
that knowledge and really dive deep into the critical post
treatment journey. This is, you know, where the
(00:43):
rubber meets the road. It really is.
We're talking practical toxicitymanagement, evidence based
follow up surveillance strategies and looking ahead.
What's next in research? That's right.
Our focus today is squarely on navigating the waters after
active treatment finishes. And frankly, that's often where
the real challenge of comprehensive care truly begins
for our patients. Definitely.
(01:05):
So to really anchor our discussion, give us a framework,
let's think about a patient scenario, one that kind of
encapsulates many of these immediate and also the long term
post treatment challenges you'llface in practice.
OK, sounds good. So let's imagine Mr. Davis.
He's 55 years old, he's HIV positive.
But, and this is important, his viral load is well controlled.
(01:26):
CD4 counts good 400 so. Reasonably healthy baseline
despite the HIV. Exactly.
He's in his final week of definitive chemo radiation for a
clinical T3 and 1B anal cancer, and as you can probably guess,
he's experiencing some significant acute toxicities.
Right at the peak time. Yeah, specifically grade 2
peroneal dermatitis and also grade 2 diarrhea.
(01:49):
He's anxious, understandably so,right?
Like many patients at this stage, of course.
And he asks us what happens after I finish.
How will you know if the treatment actually worked?
And you know what are the long term issues I need to watch out
for? And Mr. Davis's questions,
they're precisely what we need to address today.
They really highlight a criticalpoint for all of us in radiation
oncology, our role, it extends so far beyond just delivering
(02:13):
the radiation beams. It really does it.
Genuinely encompasses managing the patient's entire experience
from those acute side effects during treatment all the way
through their well, often complex long term survivorship
journey. It's about quality of life isn't
it? Not just the cure.
Absolutely. And while we've covered the
anatomy, the EPI, risk factors, pathology workup, we did that in
(02:35):
depth earlier in the series. Mr. Davis''s questions bring us
right into the practical realities of managing care after
the diagnosis and the initial treatment plan.
Right, the what now? Exactly.
So let's start with his immediate concerns.
He's in his final week. He's got this grade 2
dermatitis, grade 2 diarrhea. What's our practical aggressive
plan for managing these right now?
How do we get him through these last few days smoothly?
(02:57):
OK, good starting point. And you've hit on probably the
most common dose limiting toxicity right away that
peroneal dermatitis. It can be incredibly
debilitating for patients, effects sitting, sleeping,
hygiene, everything. So for Mr. Davis's Grade 2, that
erythema, maybe some dry disclamation.
Our management starts with emphasizing rigorous, clean
(03:20):
daily water therapy. OK.
What does that entail specifically?
Simple things really, but they have to be done consistently.
Regular sits, baths, using lukewarm water.
They're incredibly soothing, help keep the area clean.
We tell patients, you know, sit in the bath maybe 1520 minutes,
two or three times a day, or alternatively, just using a
simple Perry bottle, you know the kind they give women
(03:41):
postpartum. Use that for gentle cleansing
after every single bathroom visit.
It's crucial. It mechanically removes
irritants without any harsh scrubbing.
And beyond the cleansing itself,how do we protect that irritated
skin? Because friction must just make
it so much worse, right? Oh absolutely.
Avoiding friction is paramount. So we advise Mr. Davis and all
(04:01):
our patients wear loose fitting clothing, thick boxer shorts,
not tight briefs. You want maximum air circulation
down. There, right?
Let it breathe. Exactly and air drying the area
after baths or using the Perry bottle rather than you know,
vigorously rubbing with a towel that helps prevent more trauma
for the skin itself. We prescribe fragrance free
moisturizers, apply them frequently, keep the skin
(04:23):
supple, prevent cracking, and then a good barrier cream,
something like a zinc oxide based diaper cream or even just
a plain petroleum ointment. It's exceptionally effective at
creating that rotective layer, shielding the skin from moisture
from irritants. Alley it liberally several times
a day. That sounds like a really solid
first line for Grade 2, but let's be real, Grade 2 can
(04:45):
sometimes progress pretty quickly to grade three.
You know, moist desquamation. And that looks awful.
It feels awful for the patient. It's a real challenge.
What's our escalation plan if that happens?
Excellent question and unfortunately a very common
scenario. If we see it progressing to
moist desquamation where the skin is literally weeping
breaking down, we need to escalate immediately.
(05:07):
A modified Dakin solution soak done twice a day becomes highly
effective. Dakin's solution explain that a
bit. Sure.
Dakin's solution is basically diluted sodium hypochloric, a
very mild bleach solution. It sounds harsh, but it's
incredibly helpful. It cleans the area, reduces
bacterial colonization which is a risk for secondary infection,
(05:28):
and crucially, it helps to brideany necrotic tissue and promotes
healthy granulation tissue formation.
So you soak a gauze or a soft cloth with a Dakin solution
applied gently to the affected area for maybe 10-15 minutes.
It's truly a game changer for those severe cases.
It significantly speeds up healing and reduces pain.
We can also use topical analgesics like lidocaine gels.
(05:50):
Maybe apply them for cleansing or dressing changes just to help
manage the pain. You know when I'm trying to
remember all these steps for dermatitis, especially when
things get tough like with moistexclamation, I find mnemonics
really help lock it in. I use one I call PD Care.
Helps me cover the bases. How interesting.
Let's hear it. So P is for peri bottle and
clean water that rigorous hygiene D is for Deccan solution
(06:14):
our go to if it gets messy right.
C is for clothes, keep them loose, breathable.
A is for air drying, let the skin breathe.
R is for repairing the skin withthose moisturizers and barrier
creams, and E is for managing erythema and discomfort, maybe
with those topical analgesics. I like that PD care that's
actually quite comprehensive andeasy to recall.
(06:37):
Very useful. Yeah, it helps me.
OK, So moving on to Mr. Davis's other issue, Grade 2 diarrhea,
that can also be incredibly disruptive, especially in this
final week. What's our strategy there?
Right, diarrhea. So first we reinforce the low
residue diet. He should already be on that,
hopefully avoiding high fiber foods, dairy, spicy things.
But beyond diet, medication is key.
Lopramide. Exactly.
(06:58):
He should already be on schedule.
Lopramide. It's vital to make sure he
understands the dosing, how to titrate it.
Patients can safely take up to 4tablets a day, usually 2
milligrams each, spaced out to control frequency and urgency.
We usually start, say 2 milligrams every four to six
hours as needed, but we emphasize if it persists,
increase the frequency up to that maximum dose.
(07:20):
And if that's still not enough? Good question.
If Lobramite isn't cutting it orif there's significant cramping
and urgency, we escalate to Lomotil.
That's dephenoxylate and atropine.
The crucial point here, from ourperspective, the radiation
oncology perspective, is managing this effectively enough
to avoid a treatment break. Right, because brakes are bad.
(07:41):
Brakes are bad. Severe diarrhea can lead to
dehydration, electrolyte imbalances, or just make the
patient too uncomfortable to come in for daily radiation.
And a radiation break, even justa few days, can potentially
compromise local control. You really want to deliver that
prescribed dose as continuously as possible.
Makes sense. And Speaking of managing things
systemically without interrupting treatment,
(08:03):
Mitomycin C, it's often part of the chemo regimen with five FU
for anal cancer and it's known for being particularly
myelosuppressive. Is that a concern here in the
final week with cumulative effects?
How do we manage that? Yeah, myelosuppression is
definitely a significant concernwith mitomycin C, especially
towards the end of treatment. Yeah.
(08:24):
So for this, we're monitoring his weekly complete blood
counts, the CBCS, very, very closely.
How often is closely? Usually at least once a week,
sometimes even more frequently if we see the counts trending
downwards. The key numbers we're watching
are the absolute neutrophil count, the ANC.
OK. What are the thresholds?
If the ANC drops below say 750 or especially if it gets below
(08:46):
500, that's when we start getting seriously concerned
about increased infection risk, right?
If we were to drop below 200, that's generally our critical
threshold where medical oncologywould typically hold the
chemotherapy dose for that cycle.
But the goal is to keep the radiation going.
Absolutely. Our goal, as you said, is to
manage this very carefully to avoid interrupting the radiation
(09:07):
schedule if at all possible. We might need dose reductions
for the chemo or even hold a cycle of chemo, but we strive,
really strive to keep the radiation on schedule.
Radiation breaks tend to have a more direct and often
irreversible negative impact on local tumor control.
So chemo might pause but radiation pushes through If
feasible, what about things likeGCSF growth factors?
(09:30):
They're only prophylactic. GCSF isn't routinely used in
this setting. There are potential side
effects, and again, the primary goal is to avoid radiation
breaks. We tend to manage reactively by
holding chemo if counts drop to low, rather than using GCSF
upfront for most patients. OK, that makes sense.
So that covers managing those immediate acute challenges to
get Mr. Davis through. Now let's just ears a bit.
(09:51):
He's finished treatment, he's recovering, and he asks that
huge question, how will you knowif it worked?
And this, this is where anal cancer really stands out,
doesn't it? Compared to almost any other GI
cancer. Oh, absolutely.
It plays by his own set of rules.
This next point is arguably the single most critical piece of
knowledge that distinguishes anal cancer management from many
(10:11):
others. OK, one of the most unique and
frankly quite fascinating aspects of animal cancer is it's
remarkably slow regression aftertreatment.
It's not like say a lymphoma or even some head neck cancers
where you often see a rapid meltaway within weeks.
Right. You expect quick results
sometimes. Exactly.
But not here. This requires a significant
(10:32):
amount of patience and, crucially, really clear
communication between us and ourpatients.
So tell us about the evidence. Where does this wait and see
idea come from this 26 week rulethat gets mentioned?
Why is it so fundamental? OK, the 26 week rule, it is
absolutely foundational and it comes directly from the landmark
ACT 2 trial ACT spelled ACT. This is a big multi center
(10:54):
randomized phase three trial published in a major journal and
it gave us invaluable perspective data specifically on
response assessment in anal cancer.
And what did ACT 2 show? It showed something quite
remarkable. At three months after treatment
finished, about 50% of patients had achieved A clinical complete
response ACCR, meaning you couldn't detect the tumor
(11:16):
clinically anymore, OK. 50% at three months.
But, and this is the key part, that number didn't plateau
there. It actually rose dramatically,
up to 90% by 6 months. That's 26 weeks.
Wait, 90% from 50? That's, that's a huge jump
between three and six months. That's genuinely remarkable.
It is. And maybe the most striking
(11:36):
piece of data from ACT 2, the part that really drives our
practice is that 72%, nearly 3/4of patients who still had
clinically detectable residual disease at 11 weeks post
treatment, they went on to achieve ACCR by the 26 week mark
without any additional treatment. 72% with residual
disease at three months still got a complete response by 6
(11:57):
months. Wow.
Exactly. Think about that.
A significant chunk of patients who still had something palpable
or visible at three months ultimately achieved a complete
response if you just gave them more time.
OK, So what does that mean for managing patient anxiety during
those months? How do you counsel Mr. Davis
when he wants answers now and you're telling him we need to
(12:18):
wait maybe another three months.That 72% figure is incredibly
powerful for counseling. It directly informs our clinical
approach and maybe more importantly, how we talk to
patients. Because of this compelling
evidence, the 2025 Astro guideline Astro, pronounced like
the word Astro, makes a strong recommendation.
(12:40):
Erform close monitoring for approximately 6 months after
chemo radiation before performing a biopsy or
initiating salvage therapy for what might simply be a slow
resolving tumor. So the guideline explicitly says
wait six months before biopsy unless something's clearly
growing. Essentially, yes.
Unless there's clear evidence ofprogression, patience is the
(13:01):
recommendation. You know, I often use an analogy
for patients trying to explain this.
Think of it like developing an old school photograph in a dark
room. Remember those?
Well, when you first put the paper in the developer, you
might see faint outlines, right?An initial image starts to form.
That's like the early tumor regression.
OK, but the full crisp image, the complete picture of success,
(13:22):
it doesn't fully emerge until you give it enough time in the
chemical bath. You wouldn't pull it out after
just a minute and say, oh, it failed, would you?
No, you'd wait. You wait for the full
development time. Our treatment response in anal
cancer is remarkably similar. It's a slow reveal.
It requires patience and understanding this unique
biology. So we counsel patients like Mr.
(13:44):
Davis right from the start. We have to be patient.
We need to give the treatment time to work fully.
It's like watching a slow motionreplay.
That's a great analogy the photograph.
And we explained that what mightfeel like residual disease is
often just the slow clearing of inflammation, maybe some
necrotic tissue. Jumping to a biopsy too early
carries real risks. Unnecessary procedures, delayed
(14:06):
healing, maybe even triggering the need for a colostomy that
wasn't actually and. That really emphasizes the need
for patients backed by strong evidence.
So for the majority, that 90% who do get that clinical
complete response by 6 months, what does their surveillance
look like after that? How do we monitor them long
term? We want to catch recurrences
early but without over testing. Right.
(14:27):
Exactly. For complete responders, we
follow a specific structured schedule.
It's designed to balance that early detection with patient
convenience and avoiding unnecessary anxiety.
First, physical exams are absolutely paramount in anal
cancer surveillance. Still including the Dre.
Absolutely always includes a careful digital rectal exam, the
(14:47):
Dre, and very thorough palpationof the inguinal nodes, both
sides. Why?
Because local recurrence in the anal canal and regional nodal
recurrence in the groin are common patterns of failure, and
they're often palpable before they cause symptoms.
Makes sense? How often?
We do these exams every three months the first two years.
That's pretty intensive, reflecting that higher week of
(15:08):
recurrence early on. Then, as the risk gradually
decreases, we can space those visits out to every six to 12
months for years 2 through 3 after year three, maybe optional
annual follow up for years four and five, and often beyond,
depending on the individual patient and local practice
patterns. So what about imaging during
surveillance? Are we doing regular CT scans?
(15:30):
Is there a role for MRI or PT scans?
Yes, cross-sectional imaging is definitely a key component.
Primarily it's looking for distant metastases, liver, lungs
or maybe deeper regional nodal recurrences in the pelvis that
we might not feel on exam. OK.
We typically recommend ACT scan of the chest, abdomen and pelvis
at least annually until year 2 minimum.
(15:50):
Some guidelines or practices might go longer, maybe out to
three or even five years, but atleast two years of annual CTS is
pretty standard. And if something looks iffy on
the CT. Right.
If we see any equivocal findings, maybe a questionable
little spot in the liver or a slightly prominent
retroperitoneal node, or if the patient develops symptoms that
make us worried about the pelvis, then a pelvic MRI or a
(16:13):
PTCT can be very useful to further characterize those
findings to figure out if it's recurrence or just benign post
treatment changes. Got it.
And Speaking of PTCTS, how do weuse them for that initial
response assessment? We're waiting clinically until
six months, but is there a role for Pete earlier, maybe around
three months? Yeah, this is a bit nuanced and
(16:33):
how we use PT for response assessment has evolved.
The first restaging PT scan is typically done around the three
month mark post treatment. This often coincides that first
follow up visit where we do the endoscopy in the DRA.
Now, if that three month PT scanshows residual FTG avidity,
meaning there's still metabolic activity in the tumor area, that
could represent persistent cancer.
You don't panic. You do not panic because of
(16:56):
everything we just discussed about ACT 2 and slow regression.
If there's residual FTG avidity but clinically things seem
stable or improving and there's no clear progression, we don't
jum to conclusions. O what do you do?
The standard aroach is often to repeat the T scan, maybe in
another three months, so around the six month mark, to see if
(17:17):
that avidity is resolving. The key is to avoid premature
biopsies or salvage surgery based only on early PLE
findings. So the Astro guideline addresses
this. Yes, the Astro guideline is
clear. It says PT scans at three to
four months can help identify patients with persistent FBG
avidity who might be at higher risk, and maybe that prompts
closer follow up or earlier reevaluation around six months.
(17:39):
But it does not recommend immediate biopsy or salvage
based on an early peel alone. It helps track the trend, but
it's always interpreted in the context of that 26 week clinical
rule given the tumor time. OK.
That clarity on using PT is really important.
So we've guided Mr. Davis who treatment we've outlined how
we'll monitor his response. But his final question was about
(17:59):
those long term issues I need towatch out for.
This brings us to survivorship care.
It's our final responsibility really to prepare him and all
patients for potential long termeffects.
What are the key areas we absolutely need to counsel them
on? Survivorship care is it's just
paramount, and it covers severalreally significant areas that
can profoundly impact a patient's quality of life long
(18:22):
after the cancer is gone. First and foremost is anorectal
dysfunction. OK, what does that encompass?
Well, many patients, even if cured, will experience some
degree of long term changes in bowel function.
This can range widely. It might be long term fecal
incontinence, maybe minor issueslike trouble controlling gas or
slight soiling, or it could be significant challenges that
really impact daily life. It can also involve fibrosis, a
(18:46):
stiffening of the tissues down there, making bowel movements
difficult, causing urgency or that feeling of incomplete
evacuation. Tenesmus.
And then there's stenosis, whichis a narrowing of the anal canal
itself, which can cause pain anddifficulty passing stool.
These sound like they could be really devastating to quality of
life. They absolutely can be.
They impact self-confidence, social interactions, everything.
(19:09):
In fact, data from the big RTOG 9811 trial show that about 5% of
patients ultimately needed a permanent colostomy specifically
because of these late treatment related effects.
Wow, 5%? That's not insignificant.
Not at all. It really underscores how severe
these late effects can be. So we absolutely need to counsel
patients proactively about thesepossibilities, provide dietary
(19:31):
advice, talk about bowel regimens, medications to manage
symptoms, and crucially, consider referrals to
specialists like pelvic floor physical therapists.
OK, what about sexual dysfunction?
That's often, you know, the elephant in the room.
It's deeply personal, impacts relationships, but maybe not
always discussed openly. You're absolutely right.
It's vital we address this openly, proactively and
sensitively. Pelvic radiation, just by its
(19:54):
location, impacts the nerves andblood vessels in the pelvis that
are crucial for sexual function.For both men and women.
Yes. For men it can lead to erectile
dysfunction, changes in ejaculation.
For women, it can cause vaginal dryness, pain with intercourse,
despair, union and very importantly, vaginal stenosis
that's a narrowing and shortening of the vagina due to
(20:16):
radiation induced fibrosis. So how do we approach this
conversation? We need to have a frank, open
discussion with every single patient.
Normalize it. Make sure they feel comfortable
bringing up concerns. If they are struggling, referral
to specialist is often the next step.
Could be pelvic floor PT. Again they work on muscle
function and flexibility. Sex therapists for psychological
(20:37):
support, relationship counseling, Urologist for men,
Gynecologist for women for medical management.
Things like medications for EED or lubricants and moisturizers
for women. And you mentioned vaginal
stenosis specifically for women.Yes, and this is critical.
Counseling women on vaginal stenosis and the importance of
regular vaginal dilator use is anon negotiable part of
(20:58):
survivorship care. It really is we instruct them
how to use dilators starting several weeks after treatment
ends and continuing regularly long term to maintain vaginal
pliability and prevent severe narrowing that can make
intercourse impossible or pelvicexams difficult.
So it's a proactive measure theyneed to engage in.
Exactly, It empowers them to take an active role in managing
(21:20):
A potentially difficult side effect and it can make a huge
difference to their long term quality of life and intimacy.
We cannot understate the importance of this counseling.
That's a really crucial point. OK, moving slightly away from
the direct pelvic structures, what about other potential
issues, musculoskeletal things? I think I've heard about hip
fracture. Yes, that's another often
underappreciated late effect patients getting pelvic
(21:42):
radiation, especially for anal cancer where the dose often
includes parts of the Bony pelvis, the ischial bones,
sometimes the femoral heads. They're in an increased risk of
pelvic insufficiency fractures, including hip fractures.
Why is that? The radiation over time can
weaken the bone structure, make it more brittle.
So we should actively recommend adequate calcium and vitamin D
(22:02):
intake as just part of their routine long term health plan.
Support bone health, mitigate that risk.
Should we be screening them likewith DEXA scans?
In some cases, yes, a baseline bone density scan, a DEXA scan
might be considered, especially for older patients or those with
other risk factors. And if they have osteopenia or
osteoporosis, then interventionslike bisphosphonates might be
(22:25):
indicated. It's a simple preventative
measure, but preventing a hip fracture is incredibly important
for maintaining independence andquality of.
Life, definitely. And one last area for younger
patients, infertility. Is that something we need to
address? Absolutely.
And ideally, this conversation needs to happen before treatment
even start, during that initial consultation phase.
Because pelvic radiation. Pelvic radiation can cause
(22:47):
permanent infertility, it can damage the ovaries in women, the
testes in men. So the opportunity for fertility
preservation, sperm banking for men, egg or embryo freezing for
women needs to be presented clearly and facilitated before
chemo radiation begins. And if that didn't happen?
Well, it's a missed opportunity unfortunately, but it's still a
(23:08):
long term implication for these survivors that they should be
aware of and supportive resources can still be discussed
even after the fact. Just really speaks to the need
for that truly holistic, comprehensive pretreatment
counseling process. OK, shifting gears again.
The field is always evolving, isn't it?
Anal cancer treatment isn't static.
What are some of the key ongoingtrials looking at, say, dose
(23:31):
optimization, trying to improve that therapeutic ratio,
maximizing cure while minimizingthese side effects we've just
discussed? It sounds like we're moving
towards more personalized radiation doses.
We absolutely are. There's a significant shift
towards personalization. Try and tailor the dose to the
individual patient and tumor characteristics and there are
several really exciting developments happening right
(23:52):
now. One of the most comprehensive
programs is the UK Plato program.
It's actually a platform of related trials, ACD 3, ACT 4 and
ACT 5, all focused on personalizing the radiation
dose. ACT is pronounced ACT.
OK, tell us more about ACT 4 andACT 5 specifically.
What are they looking at? Sure.
So ECT 4 is focused on dose de escalation for patients with
(24:13):
intermediate risk disease, specifically T1 to T2, no
negative tumors. It's comparing A reduced dose
41.4 Gray to the standard dose, which is typically 50.4 Gray.
And the hypothesis is. The idea is that maybe these
smaller, no negative tumors don't actually need the full
standard dose, and using a lowerdose could significantly cut
down on long term toxicities without compromising the
(24:36):
excellent cure rates we already see for these stages.
Any early result? Yes, the early results that have
been presented look very promising.
They suggest the reduced dose iswell tolerated and achieved
similar excellent clinical complete response rates.
If the full study confirms this,it could mean significantly less
toxicity, better quality of lifefor a large group of patients.
(24:56):
That's great. And ACT 5 is that going the
other way? Exactly.
ACT 5 is looking at the other end of the spectrum, dose
escalation for advanced disease.For those larger, more
challenging tumors, like Mr. Davis's T3 and 1B case, it's
exploring doses up to 61.6 grey.Trying to improve local control
for tougher cases. Precisely the goal is to see if
(25:16):
a higher dose delivered, maybe as a simultaneously integrated
boost using modern IMRT techniques, can improve local
control and potentially survivalfor these bigger tumors, while
still keeping toxicity manageable.
So we're seeing both sides de escalation for early stage
escalation for advanced, a trulytailored approach.
Are there similar efforts happening elsewhere, maybe in
the US? Absolutely.
(25:38):
Another really important trial, this one from the US cooperative
groups is the decrease trial that's EA 2182.
It's also rigorously testing dose de escalation for T1 and T2
and zero anal cancer, much like ACT 4.
What's unique about decrease? What's interesting about
decrease is that it also includes a de intensified
chemotherapy schedule. So it's looking at reducing both
(26:01):
radiation dose and chemo intensity for this favorable
patient group. A double D intensification.
Right. Trying to hit that therapeutic
ratio from both angles, it's successful.
It could be truly transformativefor managing early stage
patients, offering potentially excellent outcomes with
substantially fewer side effects.
These trials really represent a major global effort to fine tune
(26:22):
our doses based on risk. OK.
And what about immunotherapy? It's such a hot topic everywhere
in oncology. Anal cancer seems like a prime
candidate, right? Especially with this strong HPV
link. Immunotherapy is definitely a
fascinating and rapidly evolvingarea for anal Cancer Research
and you hit the nail on the head.
The HPV link is exactly why. How does HPV make it a good
target? Well, HPV associated cancers
(26:43):
which account for the vast majority of anal cancers often
express viral proteins. These proteins can be recognized
as foreign as non self by the patient's immune system.
This makes the tumors inherentlymore immunogenic, potentially
more susceptible to immune attack.
So checkpoint inhibitors might work well.
That's the hope. Checkpoint inhibitors work by
releasing the brakes on the body's own immune system,
(27:05):
particularly T cells, allowing them to better recognize and
attack cancer cells. So several trials are actively
investigating adding these agents to our standard chemo
radiation backbone for locally advanced disease.
Can you name a couple? Sure.
For instance, trial EA 2165 is looking at adding nivolumab,
which is a PD1 inhibitor. Another trial called Tyrannis is
(27:26):
investigating a Tesla Zoomab APDL 1 inhibitor combined with
chemo radiation. And the goal is to.
The hope is that by harnessing the immune system alongside
chemo radiation, we can improve long term outcomes, maybe
increase the rate of complete responses, perhaps overcome
resistance in some patients leading to more durable cures.
It's a really significant prospect for potentially
(27:47):
enhancing our standard treatments and definitely
something we're watching very closely as the data matures.
OK, that was a lot of ground covered from immediate side
effects to long term survivorship and future
research. Let's try to distill this down
now into some absolute essentials like the high yield
clinical pearls that people should really lock in.
Absolutely. Let's nail down the key
(28:08):
takeaways, the non negotiables for managing these patients,
whether you're prepping for boards or making decisions
Monday morning in clinic. OK, Pearl number one, what is
it? Pearl 1 You absolutely must
review the new 2025 anal Cancer guidelines from Astro.
That's a STRO pronounced Astro. They're your primary evidence
(28:29):
based road map. Don't just skim it.
Seriously, sit down, grab a coffee or whatever and read it
cover to cover. It pulls together all the latest
evidence on everything from workup to follow up.
It's your compass. Got it.
Read the Astro guideline Pearl #2.
Pearl 2. Acute toxicity management is
critical, not just for comfort but for treatment integrity.
For severe perineal dermatitis, rubber PD care.
(28:51):
Or at least remember, sits, baths and deck and soaks are key
interventions. They make a huge difference.
Don't underestimate simple measures.
And for severe diarrhea, the absolute priority is to hold the
concurrent chemo if necessary before it forces a break in the
radiation schedule. Keep that radiation going if at
all possible. Continuity is paramount out for
local control. OK Pearl #3 this seems like a
(29:13):
big one based on our discussion.It is Pearl 3.
The 26 week rule. This is foundational comes
straight from ACT 2. Pronounced ACT response can be
slow. Think of that developing
photograph analogy. You must wait up to six months,
26 weeks to assess for final clinical complete response
before you jump to a biopsy for what you think might be residual
(29:33):
disease. Patience isn't just a virtue
here, it's evidence based medicine.
Avoids unnecessary interventions.
OK, Pearl #4. Pearl 4.
Late effects counseling is essential.
Proactive counseling and management are key for long term
quality of life. The big ones you have to discuss
are anoretical dysfunction, incontinence, stenosis,
fibrosis, then sexual dysfunction.
(29:54):
And critically for women you must counsel on vaginal dilator
use. It's non negotiable survivorship
care. And lastly, don't forget the
increased risk of hip fractures.Recommend calcium and vitamin D
Comprehensive survivorship care is vital.
Excellent. And the final Pearl.
Pearl #5. Pearl 5 Keep an eye on future
directions this field is moving.Know about the ongoing trials
(30:16):
like the UK Plato program, ACT 45 and the decreased trial.
They're investigating dose de escalation for early stage and
dose escalation for advanced disease.
The goal is always optimizing that therapeutic ratio.
Better outcomes, less toxicity, more personalized treatment.
Stay informed. Those are fantastic pearls.
Really captures the essence of today's discussion.
(30:37):
OK, you ready for a quick board blitz?
Test your knowledge on these concepts.
Bring it on, let's see what you've got ready for the
challenge. All right, case one, we have a
70 year old woman. She has AT2N03 centimeter anal
canal cancer. She finishes definitive chemo,
radiation gets 50.4 grey at her 12 week follow up.
So three months post treatment you do a Dre and anoscopy.
(30:58):
You note some residual firm ulcerated tissue at the primary
site. What is the most appropriate
next step? Is it A immediately schedule an
abdominoperenial resection for salvage, B perform a biopsy of
the residual tissue immediately C continue close surveillance
and re evaluate in another threemonths or D add a brecca therapy
boost to the residual disease? OK, T2 and zero 12 weeks post
(31:21):
treatment, some residual firmness and ulceration.
The answer has to be C continue close surveillance and re
evaluate in another three months.
It goes right back to Pearl 3, the 26 week rule based on ACT 2,
we know clinical complete response can take up to six
months. She's only three months.
The description is just residualfirm ulcerated tissue.
It doesn't say it's clearly progressing or growing larger
(31:41):
than baseline. So the standard guideline based
approach is patients continue course surveillance, see her
back around the six month mark. Jumping to biopsy B or salvage
surgery A right now is prematureand could lead to unnecessary
major interventions if this is just slow regression.
A brakey boost at T isn't standard practice here either,
so see in clear answer. Perfect reasoning.
(32:02):
OK, case two, you're designing an IMRT plan for a patient.
They have AT3N1A Emil cancer with an involved inguinal note.
According to the 2025 Astero guidelines, which of these
represents an appropriate dose Paying to prescription using
SIB? A45 grade to all volumes.
B 50.4 grade to the primary, 45 grade to all nodes.
C54 grade to the primary and theinvolved node. 45 grade to the
(32:26):
elective nodes, OR D 59.4 grade to the primary and 54 grade to
the involved node. 50.4 grade toelective nodes.
OK, T3 and 1A with involved inguinal node looking for an
appropriate Seb prescription perAstro.
Let's break it down. T3 needs a dose likely in the
mid to high 50s grade range. Involved node and 1A need
something like 50.4 to 54 J Elective nodes need around 36 or
(32:49):
45 J Option A is too low overall.
Option B underdose is the involved node.
Option D might be OK for the primary and involved node.
The 50.4 to elective nodes is higher than typically needed and
increases toxicity risk. Option C looks like the sweet
spot. 54 grade of the primary and the involved node.
Ghost disease and 45 grade to the elective nodes.
That fits perfectly within the Astro recommended ranges for a
(33:11):
risk adapted sick approach. So the answer is C.
Excellent breakdown. Exactly right last one case 3.
Which of the following is not a standard component of the
elective clinical target volume or CTV for a squamous cell
carcinoma of the anal canal? Is it a bilateral inguinal
nodes, B mesorectum, C para aortic nodes or D presacral
space? OK.
What's not usually in the elective CTV?
(33:32):
Bilateral inguels, definitely. In mesorectum, yes.
Standard pre sacral space, yes. Also standard periodic notes,
no, those are generally not partof the standard elective volume
for anal canal cancer. They'd only be included if there
was known disease there, or perhaps in very specific high
risk scenarios, but not routinely electively treated.
So the answer is C periodic notes.
(33:53):
Fantastic, nailed all three. OK, let's just quickly recap the
absolute key takeaways from today.
First, that 2025 escrow guideline really is our bedrock,
providing a clear evidence basedframework for management
managing anal cancer today. And 2nd, proactive aggressive
management of those acute toxicities, dermatitis,
diarrhea. It's just crucial to avoid
(34:13):
treatment breaks and keep patients on track.
Absolutely, and 3rd remember that post treatment surveillance
has to account for that unique slow regression of anal tumors.
That six month window before assessing final response is
critical. Patient saves colostomy
sometimes. And finally, comprehensive
survivorship care isn't an afterthought, it's absolutely
(34:34):
essential. Managing long term effects like
anorectal and sexual dysfunctionis key to supporting our
patients quality of life long after treatment ends.
It's truly about treating the whole person.
Well said. We really hope this discussion
has provided a solid foundation and some practical, actionable
insights for your clinical practice as you manage these
often complex but also very rewarding anal cancer patients.
(34:56):
Remember, the journey definitelydoesn't end when the radiation
stops. That's right, and you can get
show notes and complete practiceWorld Wars over at RAD on
smartlearn.com. That's RAD on smartlearn.com.
And please subscribe to RAD on Smart Review so you don't miss
our next episode. Thanks so much for tuning in.
Welcome everyone to the Radon Smart Review GI Cancer series.
We've really journeyed through the the intricate landscape of
anal cancer in our previous sessions, building quite a
robust foundation. We've explored everything from
the, you know, the fundamental anatomy and epidemiology right
through to pathology work up staging.
All the foundational pieces. Exactly.
(00:22):
And then we moved into those landmark trials, the ones that
really established definitive chemeradiation as our well, our
standard of care. We've even got into the nitty
gritty of IMRT planning. The technical side.
Yeah. So today this is part 4 and it's
crucial. Our mission is to synthesize all
that knowledge and really dive deep into the critical post
treatment journey. This is, you know, where the
(00:43):
rubber meets the road. It really is.
We're talking practical toxicitymanagement, evidence based
follow up surveillance strategies and looking ahead.
What's next in research? That's right.
Our focus today is squarely on navigating the waters after
active treatment finishes. And frankly, that's often where
the real challenge of comprehensive care truly begins
for our patients. Definitely.
(01:05):
So to really anchor our discussion, give us a framework,
let's think about a patient scenario, one that kind of
encapsulates many of these immediate and also the long term
post treatment challenges you'llface in practice.
OK, sounds good. So let's imagine Mr. Davis.
He's 55 years old, he's HIV positive.
But, and this is important, his viral load is well controlled.
(01:26):
CD4 counts good 400 so. Reasonably healthy baseline
despite the HIV. Exactly.
He's in his final week of definitive chemo radiation for a
clinical T3 and 1B anal cancer, and as you can probably guess,
he's experiencing some significant acute toxicities.
Right at the peak time. Yeah, specifically grade 2
peroneal dermatitis and also grade 2 diarrhea.
(01:49):
He's anxious, understandably so,right?
Like many patients at this stage, of course.
And he asks us what happens after I finish.
How will you know if the treatment actually worked?
And you know what are the long term issues I need to watch out
for? And Mr. Davis's questions,
they're precisely what we need to address today.
They really highlight a criticalpoint for all of us in radiation
oncology, our role, it extends so far beyond just delivering
(02:13):
the radiation beams. It really does it.
Genuinely encompasses managing the patient's entire experience
from those acute side effects during treatment all the way
through their well, often complex long term survivorship
journey. It's about quality of life isn't
it? Not just the cure.
Absolutely. And while we've covered the
anatomy, the EPI, risk factors, pathology workup, we did that in
(02:35):
depth earlier in the series. Mr. Davis''s questions bring us
right into the practical realities of managing care after
the diagnosis and the initial treatment plan.
Right, the what now? Exactly.
So let's start with his immediate concerns.
He's in his final week. He's got this grade 2
dermatitis, grade 2 diarrhea. What's our practical aggressive
plan for managing these right now?
How do we get him through these last few days smoothly?
(02:57):
OK, good starting point. And you've hit on probably the
most common dose limiting toxicity right away that
peroneal dermatitis. It can be incredibly
debilitating for patients, effects sitting, sleeping,
hygiene, everything. So for Mr. Davis's Grade 2, that
erythema, maybe some dry disclamation.
Our management starts with emphasizing rigorous, clean
(03:20):
daily water therapy. OK.
What does that entail specifically?
Simple things really, but they have to be done consistently.
Regular sits, baths, using lukewarm water.
They're incredibly soothing, help keep the area clean.
We tell patients, you know, sit in the bath maybe 1520 minutes,
two or three times a day, or alternatively, just using a
simple Perry bottle, you know the kind they give women
(03:41):
postpartum. Use that for gentle cleansing
after every single bathroom visit.
It's crucial. It mechanically removes
irritants without any harsh scrubbing.
And beyond the cleansing itself,how do we protect that irritated
skin? Because friction must just make
it so much worse, right? Oh absolutely.
Avoiding friction is paramount. So we advise Mr. Davis and all
(04:01):
our patients wear loose fitting clothing, thick boxer shorts,
not tight briefs. You want maximum air circulation
down. There, right?
Let it breathe. Exactly and air drying the area
after baths or using the Perry bottle rather than you know,
vigorously rubbing with a towel that helps prevent more trauma
for the skin itself. We prescribe fragrance free
moisturizers, apply them frequently, keep the skin
(04:23):
supple, prevent cracking, and then a good barrier cream,
something like a zinc oxide based diaper cream or even just
a plain petroleum ointment. It's exceptionally effective at
creating that rotective layer, shielding the skin from moisture
from irritants. Alley it liberally several times
a day. That sounds like a really solid
first line for Grade 2, but let's be real, Grade 2 can
(04:45):
sometimes progress pretty quickly to grade three.
You know, moist desquamation. And that looks awful.
It feels awful for the patient. It's a real challenge.
What's our escalation plan if that happens?
Excellent question and unfortunately a very common
scenario. If we see it progressing to
moist desquamation where the skin is literally weeping
breaking down, we need to escalate immediately.
(05:07):
A modified Dakin solution soak done twice a day becomes highly
effective. Dakin's solution explain that a
bit. Sure.
Dakin's solution is basically diluted sodium hypochloric, a
very mild bleach solution. It sounds harsh, but it's
incredibly helpful. It cleans the area, reduces
bacterial colonization which is a risk for secondary infection,
(05:28):
and crucially, it helps to brideany necrotic tissue and promotes
healthy granulation tissue formation.
So you soak a gauze or a soft cloth with a Dakin solution
applied gently to the affected area for maybe 10-15 minutes.
It's truly a game changer for those severe cases.
It significantly speeds up healing and reduces pain.
We can also use topical analgesics like lidocaine gels.
(05:50):
Maybe apply them for cleansing or dressing changes just to help
manage the pain. You know when I'm trying to
remember all these steps for dermatitis, especially when
things get tough like with moistexclamation, I find mnemonics
really help lock it in. I use one I call PD Care.
Helps me cover the bases. How interesting.
Let's hear it. So P is for peri bottle and
clean water that rigorous hygiene D is for Deccan solution
(06:14):
our go to if it gets messy right.
C is for clothes, keep them loose, breathable.
A is for air drying, let the skin breathe.
R is for repairing the skin withthose moisturizers and barrier
creams, and E is for managing erythema and discomfort, maybe
with those topical analgesics. I like that PD care that's
actually quite comprehensive andeasy to recall.
(06:37):
Very useful. Yeah, it helps me.
OK, So moving on to Mr. Davis's other issue, Grade 2 diarrhea,
that can also be incredibly disruptive, especially in this
final week. What's our strategy there?
Right, diarrhea. So first we reinforce the low
residue diet. He should already be on that,
hopefully avoiding high fiber foods, dairy, spicy things.
But beyond diet, medication is key.
Lopramide. Exactly.
(06:58):
He should already be on schedule.
Lopramide. It's vital to make sure he
understands the dosing, how to titrate it.
Patients can safely take up to 4tablets a day, usually 2
milligrams each, spaced out to control frequency and urgency.
We usually start, say 2 milligrams every four to six
hours as needed, but we emphasize if it persists,
increase the frequency up to that maximum dose.
(07:20):
And if that's still not enough? Good question.
If Lobramite isn't cutting it orif there's significant cramping
and urgency, we escalate to Lomotil.
That's dephenoxylate and atropine.
The crucial point here, from ourperspective, the radiation
oncology perspective, is managing this effectively enough
to avoid a treatment break. Right, because brakes are bad.
(07:41):
Brakes are bad. Severe diarrhea can lead to
dehydration, electrolyte imbalances, or just make the
patient too uncomfortable to come in for daily radiation.
And a radiation break, even justa few days, can potentially
compromise local control. You really want to deliver that
prescribed dose as continuously as possible.
Makes sense. And Speaking of managing things
systemically without interrupting treatment,
(08:03):
Mitomycin C, it's often part of the chemo regimen with five FU
for anal cancer and it's known for being particularly
myelosuppressive. Is that a concern here in the
final week with cumulative effects?
How do we manage that? Yeah, myelosuppression is
definitely a significant concernwith mitomycin C, especially
towards the end of treatment. Yeah.
(08:24):
So for this, we're monitoring his weekly complete blood
counts, the CBCS, very, very closely.
How often is closely? Usually at least once a week,
sometimes even more frequently if we see the counts trending
downwards. The key numbers we're watching
are the absolute neutrophil count, the ANC.
OK. What are the thresholds?
If the ANC drops below say 750 or especially if it gets below
(08:46):
500, that's when we start getting seriously concerned
about increased infection risk, right?
If we were to drop below 200, that's generally our critical
threshold where medical oncologywould typically hold the
chemotherapy dose for that cycle.
But the goal is to keep the radiation going.
Absolutely. Our goal, as you said, is to
manage this very carefully to avoid interrupting the radiation
(09:07):
schedule if at all possible. We might need dose reductions
for the chemo or even hold a cycle of chemo, but we strive,
really strive to keep the radiation on schedule.
Radiation breaks tend to have a more direct and often
irreversible negative impact on local tumor control.
So chemo might pause but radiation pushes through If
feasible, what about things likeGCSF growth factors?
(09:30):
They're only prophylactic. GCSF isn't routinely used in
this setting. There are potential side
effects, and again, the primary goal is to avoid radiation
breaks. We tend to manage reactively by
holding chemo if counts drop to low, rather than using GCSF
upfront for most patients. OK, that makes sense.
So that covers managing those immediate acute challenges to
get Mr. Davis through. Now let's just ears a bit.
(09:51):
He's finished treatment, he's recovering, and he asks that
huge question, how will you knowif it worked?
And this, this is where anal cancer really stands out,
doesn't it? Compared to almost any other GI
cancer. Oh, absolutely.
It plays by his own set of rules.
This next point is arguably the single most critical piece of
knowledge that distinguishes anal cancer management from many
(10:11):
others. OK, one of the most unique and
frankly quite fascinating aspects of animal cancer is it's
remarkably slow regression aftertreatment.
It's not like say a lymphoma or even some head neck cancers
where you often see a rapid meltaway within weeks.
Right. You expect quick results
sometimes. Exactly.
But not here. This requires a significant
(10:32):
amount of patience and, crucially, really clear
communication between us and ourpatients.
So tell us about the evidence. Where does this wait and see
idea come from this 26 week rulethat gets mentioned?
Why is it so fundamental? OK, the 26 week rule, it is
absolutely foundational and it comes directly from the landmark
ACT 2 trial ACT spelled ACT. This is a big multi center
(10:54):
randomized phase three trial published in a major journal and
it gave us invaluable perspective data specifically on
response assessment in anal cancer.
And what did ACT 2 show? It showed something quite
remarkable. At three months after treatment
finished, about 50% of patients had achieved A clinical complete
response ACCR, meaning you couldn't detect the tumor
(11:16):
clinically anymore, OK. 50% at three months.
But, and this is the key part, that number didn't plateau
there. It actually rose dramatically,
up to 90% by 6 months. That's 26 weeks.
Wait, 90% from 50? That's, that's a huge jump
between three and six months. That's genuinely remarkable.
It is. And maybe the most striking
(11:36):
piece of data from ACT 2, the part that really drives our
practice is that 72%, nearly 3/4of patients who still had
clinically detectable residual disease at 11 weeks post
treatment, they went on to achieve ACCR by the 26 week mark
without any additional treatment. 72% with residual
disease at three months still got a complete response by 6
(11:57):
months. Wow.
Exactly. Think about that.
A significant chunk of patients who still had something palpable
or visible at three months ultimately achieved a complete
response if you just gave them more time.
OK, So what does that mean for managing patient anxiety during
those months? How do you counsel Mr. Davis
when he wants answers now and you're telling him we need to
(12:18):
wait maybe another three months.That 72% figure is incredibly
powerful for counseling. It directly informs our clinical
approach and maybe more importantly, how we talk to
patients. Because of this compelling
evidence, the 2025 Astro guideline Astro, pronounced like
the word Astro, makes a strong recommendation.
(12:40):
Erform close monitoring for approximately 6 months after
chemo radiation before performing a biopsy or
initiating salvage therapy for what might simply be a slow
resolving tumor. So the guideline explicitly says
wait six months before biopsy unless something's clearly
growing. Essentially, yes.
Unless there's clear evidence ofprogression, patience is the
(13:01):
recommendation. You know, I often use an analogy
for patients trying to explain this.
Think of it like developing an old school photograph in a dark
room. Remember those?
Well, when you first put the paper in the developer, you
might see faint outlines, right?An initial image starts to form.
That's like the early tumor regression.
OK, but the full crisp image, the complete picture of success,
(13:22):
it doesn't fully emerge until you give it enough time in the
chemical bath. You wouldn't pull it out after
just a minute and say, oh, it failed, would you?
No, you'd wait. You wait for the full
development time. Our treatment response in anal
cancer is remarkably similar. It's a slow reveal.
It requires patience and understanding this unique
biology. So we counsel patients like Mr.
(13:44):
Davis right from the start. We have to be patient.
We need to give the treatment time to work fully.
It's like watching a slow motionreplay.
That's a great analogy the photograph.
And we explained that what mightfeel like residual disease is
often just the slow clearing of inflammation, maybe some
necrotic tissue. Jumping to a biopsy too early
carries real risks. Unnecessary procedures, delayed
(14:06):
healing, maybe even triggering the need for a colostomy that
wasn't actually and. That really emphasizes the need
for patients backed by strong evidence.
So for the majority, that 90% who do get that clinical
complete response by 6 months, what does their surveillance
look like after that? How do we monitor them long
term? We want to catch recurrences
early but without over testing. Right.
(14:27):
Exactly. For complete responders, we
follow a specific structured schedule.
It's designed to balance that early detection with patient
convenience and avoiding unnecessary anxiety.
First, physical exams are absolutely paramount in anal
cancer surveillance. Still including the Dre.
Absolutely always includes a careful digital rectal exam, the
(14:47):
Dre, and very thorough palpationof the inguinal nodes, both
sides. Why?
Because local recurrence in the anal canal and regional nodal
recurrence in the groin are common patterns of failure, and
they're often palpable before they cause symptoms.
Makes sense? How often?
We do these exams every three months the first two years.
That's pretty intensive, reflecting that higher week of
(15:08):
recurrence early on. Then, as the risk gradually
decreases, we can space those visits out to every six to 12
months for years 2 through 3 after year three, maybe optional
annual follow up for years four and five, and often beyond,
depending on the individual patient and local practice
patterns. So what about imaging during
surveillance? Are we doing regular CT scans?
(15:30):
Is there a role for MRI or PT scans?
Yes, cross-sectional imaging is definitely a key component.
Primarily it's looking for distant metastases, liver, lungs
or maybe deeper regional nodal recurrences in the pelvis that
we might not feel on exam. OK.
We typically recommend ACT scan of the chest, abdomen and pelvis
at least annually until year 2 minimum.
(15:50):
Some guidelines or practices might go longer, maybe out to
three or even five years, but atleast two years of annual CTS is
pretty standard. And if something looks iffy on
the CT. Right.
If we see any equivocal findings, maybe a questionable
little spot in the liver or a slightly prominent
retroperitoneal node, or if the patient develops symptoms that
make us worried about the pelvis, then a pelvic MRI or a
(16:13):
PTCT can be very useful to further characterize those
findings to figure out if it's recurrence or just benign post
treatment changes. Got it.
And Speaking of PTCTS, how do weuse them for that initial
response assessment? We're waiting clinically until
six months, but is there a role for Pete earlier, maybe around
three months? Yeah, this is a bit nuanced and
(16:33):
how we use PT for response assessment has evolved.
The first restaging PT scan is typically done around the three
month mark post treatment. This often coincides that first
follow up visit where we do the endoscopy in the DRA.
Now, if that three month PT scanshows residual FTG avidity,
meaning there's still metabolic activity in the tumor area, that
could represent persistent cancer.
You don't panic. You do not panic because of
(16:56):
everything we just discussed about ACT 2 and slow regression.
If there's residual FTG avidity but clinically things seem
stable or improving and there's no clear progression, we don't
jum to conclusions. O what do you do?
The standard aroach is often to repeat the T scan, maybe in
another three months, so around the six month mark, to see if
(17:17):
that avidity is resolving. The key is to avoid premature
biopsies or salvage surgery based only on early PLE
findings. So the Astro guideline addresses
this. Yes, the Astro guideline is
clear. It says PT scans at three to
four months can help identify patients with persistent FBG
avidity who might be at higher risk, and maybe that prompts
closer follow up or earlier reevaluation around six months.
(17:39):
But it does not recommend immediate biopsy or salvage
based on an early peel alone. It helps track the trend, but
it's always interpreted in the context of that 26 week clinical
rule given the tumor time. OK.
That clarity on using PT is really important.
So we've guided Mr. Davis who treatment we've outlined how
we'll monitor his response. But his final question was about
(17:59):
those long term issues I need towatch out for.
This brings us to survivorship care.
It's our final responsibility really to prepare him and all
patients for potential long termeffects.
What are the key areas we absolutely need to counsel them
on? Survivorship care is it's just
paramount, and it covers severalreally significant areas that
can profoundly impact a patient's quality of life long
(18:22):
after the cancer is gone. First and foremost is anorectal
dysfunction. OK, what does that encompass?
Well, many patients, even if cured, will experience some
degree of long term changes in bowel function.
This can range widely. It might be long term fecal
incontinence, maybe minor issueslike trouble controlling gas or
slight soiling, or it could be significant challenges that
really impact daily life. It can also involve fibrosis, a
(18:46):
stiffening of the tissues down there, making bowel movements
difficult, causing urgency or that feeling of incomplete
evacuation. Tenesmus.
And then there's stenosis, whichis a narrowing of the anal canal
itself, which can cause pain anddifficulty passing stool.
These sound like they could be really devastating to quality of
life. They absolutely can be.
They impact self-confidence, social interactions, everything.
(19:09):
In fact, data from the big RTOG 9811 trial show that about 5% of
patients ultimately needed a permanent colostomy specifically
because of these late treatment related effects.
Wow, 5%? That's not insignificant.
Not at all. It really underscores how severe
these late effects can be. So we absolutely need to counsel
patients proactively about thesepossibilities, provide dietary
(19:31):
advice, talk about bowel regimens, medications to manage
symptoms, and crucially, consider referrals to
specialists like pelvic floor physical therapists.
OK, what about sexual dysfunction?
That's often, you know, the elephant in the room.
It's deeply personal, impacts relationships, but maybe not
always discussed openly. You're absolutely right.
It's vital we address this openly, proactively and
sensitively. Pelvic radiation, just by its
(19:54):
location, impacts the nerves andblood vessels in the pelvis that
are crucial for sexual function.For both men and women.
Yes. For men it can lead to erectile
dysfunction, changes in ejaculation.
For women, it can cause vaginal dryness, pain with intercourse,
despair, union and very importantly, vaginal stenosis
that's a narrowing and shortening of the vagina due to
(20:16):
radiation induced fibrosis. So how do we approach this
conversation? We need to have a frank, open
discussion with every single patient.
Normalize it. Make sure they feel comfortable
bringing up concerns. If they are struggling, referral
to specialist is often the next step.
Could be pelvic floor PT. Again they work on muscle
function and flexibility. Sex therapists for psychological
(20:37):
support, relationship counseling, Urologist for men,
Gynecologist for women for medical management.
Things like medications for EED or lubricants and moisturizers
for women. And you mentioned vaginal
stenosis specifically for women.Yes, and this is critical.
Counseling women on vaginal stenosis and the importance of
regular vaginal dilator use is anon negotiable part of
(20:58):
survivorship care. It really is we instruct them
how to use dilators starting several weeks after treatment
ends and continuing regularly long term to maintain vaginal
pliability and prevent severe narrowing that can make
intercourse impossible or pelvicexams difficult.
So it's a proactive measure theyneed to engage in.
Exactly, It empowers them to take an active role in managing
(21:20):
A potentially difficult side effect and it can make a huge
difference to their long term quality of life and intimacy.
We cannot understate the importance of this counseling.
That's a really crucial point. OK, moving slightly away from
the direct pelvic structures, what about other potential
issues, musculoskeletal things? I think I've heard about hip
fracture. Yes, that's another often
underappreciated late effect patients getting pelvic
(21:42):
radiation, especially for anal cancer where the dose often
includes parts of the Bony pelvis, the ischial bones,
sometimes the femoral heads. They're in an increased risk of
pelvic insufficiency fractures, including hip fractures.
Why is that? The radiation over time can
weaken the bone structure, make it more brittle.
So we should actively recommend adequate calcium and vitamin D
(22:02):
intake as just part of their routine long term health plan.
Support bone health, mitigate that risk.
Should we be screening them likewith DEXA scans?
In some cases, yes, a baseline bone density scan, a DEXA scan
might be considered, especially for older patients or those with
other risk factors. And if they have osteopenia or
osteoporosis, then interventionslike bisphosphonates might be
(22:25):
indicated. It's a simple preventative
measure, but preventing a hip fracture is incredibly important
for maintaining independence andquality of.
Life, definitely. And one last area for younger
patients, infertility. Is that something we need to
address? Absolutely.
And ideally, this conversation needs to happen before treatment
even start, during that initial consultation phase.
Because pelvic radiation. Pelvic radiation can cause
(22:47):
permanent infertility, it can damage the ovaries in women, the
testes in men. So the opportunity for fertility
preservation, sperm banking for men, egg or embryo freezing for
women needs to be presented clearly and facilitated before
chemo radiation begins. And if that didn't happen?
Well, it's a missed opportunity unfortunately, but it's still a
(23:08):
long term implication for these survivors that they should be
aware of and supportive resources can still be discussed
even after the fact. Just really speaks to the need
for that truly holistic, comprehensive pretreatment
counseling process. OK, shifting gears again.
The field is always evolving, isn't it?
Anal cancer treatment isn't static.
What are some of the key ongoingtrials looking at, say, dose
(23:31):
optimization, trying to improve that therapeutic ratio,
maximizing cure while minimizingthese side effects we've just
discussed? It sounds like we're moving
towards more personalized radiation doses.
We absolutely are. There's a significant shift
towards personalization. Try and tailor the dose to the
individual patient and tumor characteristics and there are
several really exciting developments happening right
(23:52):
now. One of the most comprehensive
programs is the UK Plato program.
It's actually a platform of related trials, ACD 3, ACT 4 and
ACT 5, all focused on personalizing the radiation
dose. ACT is pronounced ACT.
OK, tell us more about ACT 4 andACT 5 specifically.
What are they looking at? Sure.
So ECT 4 is focused on dose de escalation for patients with
(24:13):
intermediate risk disease, specifically T1 to T2, no
negative tumors. It's comparing A reduced dose
41.4 Gray to the standard dose, which is typically 50.4 Gray.
And the hypothesis is. The idea is that maybe these
smaller, no negative tumors don't actually need the full
standard dose, and using a lowerdose could significantly cut
down on long term toxicities without compromising the
(24:36):
excellent cure rates we already see for these stages.
Any early result? Yes, the early results that have
been presented look very promising.
They suggest the reduced dose iswell tolerated and achieved
similar excellent clinical complete response rates.
If the full study confirms this,it could mean significantly less
toxicity, better quality of lifefor a large group of patients.
(24:56):
That's great. And ACT 5 is that going the
other way? Exactly.
ACT 5 is looking at the other end of the spectrum, dose
escalation for advanced disease.For those larger, more
challenging tumors, like Mr. Davis's T3 and 1B case, it's
exploring doses up to 61.6 grey.Trying to improve local control
for tougher cases. Precisely the goal is to see if
(25:16):
a higher dose delivered, maybe as a simultaneously integrated
boost using modern IMRT techniques, can improve local
control and potentially survivalfor these bigger tumors, while
still keeping toxicity manageable.
So we're seeing both sides de escalation for early stage
escalation for advanced, a trulytailored approach.
Are there similar efforts happening elsewhere, maybe in
the US? Absolutely.
(25:38):
Another really important trial, this one from the US cooperative
groups is the decrease trial that's EA 2182.
It's also rigorously testing dose de escalation for T1 and T2
and zero anal cancer, much like ACT 4.
What's unique about decrease? What's interesting about
decrease is that it also includes a de intensified
chemotherapy schedule. So it's looking at reducing both
(26:01):
radiation dose and chemo intensity for this favorable
patient group. A double D intensification.
Right. Trying to hit that therapeutic
ratio from both angles, it's successful.
It could be truly transformativefor managing early stage
patients, offering potentially excellent outcomes with
substantially fewer side effects.
These trials really represent a major global effort to fine tune
(26:22):
our doses based on risk. OK.
And what about immunotherapy? It's such a hot topic everywhere
in oncology. Anal cancer seems like a prime
candidate, right? Especially with this strong HPV
link. Immunotherapy is definitely a
fascinating and rapidly evolvingarea for anal Cancer Research
and you hit the nail on the head.
The HPV link is exactly why. How does HPV make it a good
target? Well, HPV associated cancers
(26:43):
which account for the vast majority of anal cancers often
express viral proteins. These proteins can be recognized
as foreign as non self by the patient's immune system.
This makes the tumors inherentlymore immunogenic, potentially
more susceptible to immune attack.
So checkpoint inhibitors might work well.
That's the hope. Checkpoint inhibitors work by
releasing the brakes on the body's own immune system,
(27:05):
particularly T cells, allowing them to better recognize and
attack cancer cells. So several trials are actively
investigating adding these agents to our standard chemo
radiation backbone for locally advanced disease.
Can you name a couple? Sure.
For instance, trial EA 2165 is looking at adding nivolumab,
which is a PD1 inhibitor. Another trial called Tyrannis is
(27:26):
investigating a Tesla Zoomab APDL 1 inhibitor combined with
chemo radiation. And the goal is to.
The hope is that by harnessing the immune system alongside
chemo radiation, we can improve long term outcomes, maybe
increase the rate of complete responses, perhaps overcome
resistance in some patients leading to more durable cures.
It's a really significant prospect for potentially
(27:47):
enhancing our standard treatments and definitely
something we're watching very closely as the data matures.
OK, that was a lot of ground covered from immediate side
effects to long term survivorship and future
research. Let's try to distill this down
now into some absolute essentials like the high yield
clinical pearls that people should really lock in.
Absolutely. Let's nail down the key
(28:08):
takeaways, the non negotiables for managing these patients,
whether you're prepping for boards or making decisions
Monday morning in clinic. OK, Pearl number one, what is
it? Pearl 1 You absolutely must
review the new 2025 anal Cancer guidelines from Astro.
That's a STRO pronounced Astro. They're your primary evidence
(28:29):
based road map. Don't just skim it.
Seriously, sit down, grab a coffee or whatever and read it
cover to cover. It pulls together all the latest
evidence on everything from workup to follow up.
It's your compass. Got it.
Read the Astro guideline Pearl #2.
Pearl 2. Acute toxicity management is
critical, not just for comfort but for treatment integrity.
For severe perineal dermatitis, rubber PD care.
(28:51):
Or at least remember, sits, baths and deck and soaks are key
interventions. They make a huge difference.
Don't underestimate simple measures.
And for severe diarrhea, the absolute priority is to hold the
concurrent chemo if necessary before it forces a break in the
radiation schedule. Keep that radiation going if at
all possible. Continuity is paramount out for
local control. OK Pearl #3 this seems like a
(29:13):
big one based on our discussion.It is Pearl 3.
The 26 week rule. This is foundational comes
straight from ACT 2. Pronounced ACT response can be
slow. Think of that developing
photograph analogy. You must wait up to six months,
26 weeks to assess for final clinical complete response
before you jump to a biopsy for what you think might be residual
(29:33):
disease. Patience isn't just a virtue
here, it's evidence based medicine.
Avoids unnecessary interventions.
OK, Pearl #4. Pearl 4.
Late effects counseling is essential.
Proactive counseling and management are key for long term
quality of life. The big ones you have to discuss
are anoretical dysfunction, incontinence, stenosis,
fibrosis, then sexual dysfunction.
(29:54):
And critically for women you must counsel on vaginal dilator
use. It's non negotiable survivorship
care. And lastly, don't forget the
increased risk of hip fractures.Recommend calcium and vitamin D
Comprehensive survivorship care is vital.
Excellent. And the final Pearl.
Pearl #5. Pearl 5 Keep an eye on future
directions this field is moving.Know about the ongoing trials
(30:16):
like the UK Plato program, ACT 45 and the decreased trial.
They're investigating dose de escalation for early stage and
dose escalation for advanced disease.
The goal is always optimizing that therapeutic ratio.
Better outcomes, less toxicity, more personalized treatment.
Stay informed. Those are fantastic pearls.
Really captures the essence of today's discussion.
(30:37):
OK, you ready for a quick board blitz?
Test your knowledge on these concepts.
Bring it on, let's see what you've got ready for the
challenge. All right, case one, we have a
70 year old woman. She has AT2N03 centimeter anal
canal cancer. She finishes definitive chemo,
radiation gets 50.4 grey at her 12 week follow up.
So three months post treatment you do a Dre and anoscopy.
(30:58):
You note some residual firm ulcerated tissue at the primary
site. What is the most appropriate
next step? Is it A immediately schedule an
abdominoperenial resection for salvage, B perform a biopsy of
the residual tissue immediately C continue close surveillance
and re evaluate in another threemonths or D add a brecca therapy
boost to the residual disease? OK, T2 and zero 12 weeks post
(31:21):
treatment, some residual firmness and ulceration.
The answer has to be C continue close surveillance and re
evaluate in another three months.
It goes right back to Pearl 3, the 26 week rule based on ACT 2,
we know clinical complete response can take up to six
months. She's only three months.
The description is just residualfirm ulcerated tissue.
It doesn't say it's clearly progressing or growing larger
(31:41):
than baseline. So the standard guideline based
approach is patients continue course surveillance, see her
back around the six month mark. Jumping to biopsy B or salvage
surgery A right now is prematureand could lead to unnecessary
major interventions if this is just slow regression.
A brakey boost at T isn't standard practice here either,
so see in clear answer. Perfect reasoning.
(32:02):
OK, case two, you're designing an IMRT plan for a patient.
They have AT3N1A Emil cancer with an involved inguinal note.
According to the 2025 Astero guidelines, which of these
represents an appropriate dose Paying to prescription using
SIB? A45 grade to all volumes.
B 50.4 grade to the primary, 45 grade to all nodes.
C54 grade to the primary and theinvolved node. 45 grade to the
(32:26):
elective nodes, OR D 59.4 grade to the primary and 54 grade to
the involved node. 50.4 grade toelective nodes.
OK, T3 and 1A with involved inguinal node looking for an
appropriate Seb prescription perAstro.
Let's break it down. T3 needs a dose likely in the
mid to high 50s grade range. Involved node and 1A need
something like 50.4 to 54 J Elective nodes need around 36 or
(32:49):
45 J Option A is too low overall.
Option B underdose is the involved node.
Option D might be OK for the primary and involved node.
The 50.4 to elective nodes is higher than typically needed and
increases toxicity risk. Option C looks like the sweet
spot. 54 grade of the primary and the involved node.
Ghost disease and 45 grade to the elective nodes.
That fits perfectly within the Astro recommended ranges for a
(33:11):
risk adapted sick approach. So the answer is C.
Excellent breakdown. Exactly right last one case 3.
Which of the following is not a standard component of the
elective clinical target volume or CTV for a squamous cell
carcinoma of the anal canal? Is it a bilateral inguinal
nodes, B mesorectum, C para aortic nodes or D presacral
space? OK.
What's not usually in the elective CTV?
(33:32):
Bilateral inguels, definitely. In mesorectum, yes.
Standard pre sacral space, yes. Also standard periodic notes,
no, those are generally not partof the standard elective volume
for anal canal cancer. They'd only be included if there
was known disease there, or perhaps in very specific high
risk scenarios, but not routinely electively treated.
So the answer is C periodic notes.
(33:53):
Fantastic, nailed all three. OK, let's just quickly recap the
absolute key takeaways from today.
First, that 2025 escrow guideline really is our bedrock,
providing a clear evidence basedframework for management
managing anal cancer today. And 2nd, proactive aggressive
management of those acute toxicities, dermatitis,
diarrhea. It's just crucial to avoid
(34:13):
treatment breaks and keep patients on track.
Absolutely, and 3rd remember that post treatment surveillance
has to account for that unique slow regression of anal tumors.
That six month window before assessing final response is
critical. Patient saves colostomy
sometimes. And finally, comprehensive
survivorship care isn't an afterthought, it's absolutely
(34:34):
essential. Managing long term effects like
anorectal and sexual dysfunctionis key to supporting our
patients quality of life long after treatment ends.
It's truly about treating the whole person.
Well said. We really hope this discussion
has provided a solid foundation and some practical, actionable
insights for your clinical practice as you manage these
often complex but also very rewarding anal cancer patients.
(34:56):
Remember, the journey definitelydoesn't end when the radiation
stops. That's right, and you can get
show notes and complete practiceWorld Wars over at RAD on
smartlearn.com. That's RAD on smartlearn.com.
And please subscribe to RAD on Smart Review so you don't miss
our next episode. Thanks so much for tuning in.
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