Anal Cancer Management

Hello everybody and welcome to this tutorial on anal cancer

management. So just to overview, we're going to look at

a little bit of anatomy and physiology, epidemiology, etiology, staging

and grading management, treatment related side effects and some old

exam style questions that might be helpful to you to

ensure that you can understand the information that we're going

to discuss today.

As always.

If there is anything that you are unclear about any

additional support you need.

If you want to discuss anything in relation to anal

cancer management then please just email me.

Okay so to start with could you label this next

diagram? Might be useful to pause the video now on

this and see what you can remember.

Okay here are the labels for the diagram.

So just picking out gross structures associated with large and

small bowel and the G.

I. Tract itself.

Basic level information just to help you navigate.

Could you label this next diagram, pause the video now.

Okay here's a diagram and here are the answers.

Can you remember anything about digestion?

I wonder if you could briefly just use a pen

and paper and write yourself a paragraph describing the main

steps in the process of digestion.

Okay the next couple of slides will help you remember

some aspects of the process of digestion.

It's not really something that we would examine you on.

It's just good to be aware.

Yeah so I'll let you read through those in your

own time.

So this diagram here shows anatomy of the rectum and

anus and the most inferior or distal part um is

a rectum And then obviously we've got the the anus

and anal canal.

Um I need you to be aware that it's a

highly vascular structure.

It's got a really good blood supply.

It's muscular as well because of the job that it

does. And point out as well some unique uh bits

of anatomy associated with function and those being sphincters, external

and internal sphincters which as you know, are responsible for

maintaining our continents and are an important consideration when you

come to think about management and the effect that different

approaches can have on stink to function and preservation in

general. And in turn then associated quality of life questions

that you might need to be mindful of.

So the anal canal as you know, runs down and

back. It's about 3-4 cm long extending from the rectum

to the junction with the hair bearing skin of the

peri anal region.

The peri anal area is what we describe as the

five centimeter area around the anal verge.

So you'll be used to seeing patients possibly in a

prone position visualizing and seeing the anal cleft um And

the anal verge itself.

And we describe the peri anal region as the five

centimeter radius around that.

And it's quite often this peri anal area that will

suffer with skin reaction.

The anal verge is the skin adjacent to the very

end point of the canal.

In terms of histology.

Then the skin in this peri anal region is similar

to the hair bearing skin that you'll find elsewhere in

the body.

The lower end is comprised of squamous epithelium and just

below the pep Tate line emerges with a different type

of uh cell type called transitional epithelium.

And there's a transitional zone here that extends approximately for

about two cm.

And then you've got a mix.

Then a glandular can columna mucosa of the rectum.

The different histological cell types then obviously would help you

think about potentially a cancer occurring from different regions and

then being of a different histology type because of the

cell that they've generated from.

So the peck take line as you know, divides the

upper two thirds and the lower third of the anal

canal. And it's where you've got this transition zone and

a change in histological cell type, the anal canal.

So the walls, as we pointed out before a composed

of internal sphincter and external sphincter.

And there are a couple of major lymphatic pathways that

I need you to be aware of.

Um they're not exclusive and there's a couple of connections

but just to be mindful and be able to call

to mind um some key terms associated with drainage here.

So drainage from the upper canal will head towards peri

rectal and hemorrhoid, all amazing terek nodes.

Around and above the peptic line.

We're heading to the internal paladino and hyper gastric and

operator. And then iliac nodes, the distal end the virgin

the peri anal skin.

We've got drainage to inferior, sorry superficial inguinal nodes and

then occasionally to federal and then external iliac nodes.

So just to be mindful of the different routes associated

with the different sections of the canal.

Um And where uh potentially olympic and drain too.

And then I guess in the context of cancer where

you might see an enlarged node.

So anal cancer you tend to see more cancers presenting

in the canal than in the peri anal skin itself.

The majority of squamous cell carcinomas.

There are a couple of different subtypes that you will

see rarely.

Um And they can be large cell characterizing.

Large sell non certain characterizing and basil Lloyd.

A small minority can be adenocarcinoma as as well.

You might see some melanomas thrown into the mix but

again rare.

Most are squamous cell carcinomas.

Um Peri anal skin.

So you are occurring in this area tend to be

SCC. Um And sometimes BCC you do get this carcinoma

is that you are anal dysplasia and that's similar to

what you have covered in relation to cervical cancer.

Um So this kind of pre cancerous condition.

So in terms of then let's look at epidemiology.

So incidents of anal cancers.

Can you recall from your own clinical experience any anal

cancer patients that you might have participated in caring for

numbers are very small.

Just over.

Well we've got a slightly increased year on year but

taken 2020 We've got a total of should be 1400,

not 14,484 cases.

Um accounting for only 1% of total cancers.

Most are diagnosed in people who are over 60.

A slight difference in the ratio between males and females

and the peri, anal tumors tend to be more common

in men.

So here we've got the right number somewhere around 1,438

cases in 2016.

And that was taken from Mylan.

Um It's difficult to find data and anal cancers because

the numbers are so small.

Um In males are about 500 cases in 2016, females,

about nine, About half of cases are in people over

65. And you've got a high rate of anal cancer

in people age 90 plus Year on year, we've seen

an increase.

So since the 70s, incidents rates have more than doubled

in the UKK and there's a greater increase in females

where it's almost tripled.

It's an important consideration.

Then this difference between male and female incident rates.

So we've got, we can see the pink line here

indicating female incident rates.

The blue line indicating males.

And then over a number of people, we've got a

steady sort of increased like dip there obviously.

But general trend towards an increase in females and a

little bit more of a leveling out in males over

the last decade, we've got an increase overall and Stired

rates in male as we said in a steady increase

in females.

We've interestingly got a projected increase in anal cancer incidents

between 2014 and 2035.

We expected it to rise by 43 and percent and

then a little slight dip.

Then beyond that.

So one in 795 men and one in 4 70

women will be diagnosed with an anal cancer in their

lifetime. And there is a correlation we can see in

the data between presentation and incidents in people living in

the most deprived areas.

So look like with rectal cancer.

This correlation and association between incidence rates and poverty and

deprivation. So thinking about the area of the body that

we're talking about and the job that it does.

I wonder if you can think as well about any

possible ideological factors that can be associated with an anal

cancer. I'll just give you a minute there to think

about that and write something down.

So pause the video.

Okay, so majority of cancers presenting or occurring in the

anal canal are thought to be associated with HPV human

papilloma virus.

We think there's an association between sexually transmitted factors.

Um the data shows that there is an increased risk

of anal cancer if the person has a history of

anal receptive or engaging in a in a receptive intercourse.

People who have multiple sexual partners.

Again, this correlation between sexually transmitted factors at play here

and several sexually transmitted viral and bacterial infections and history

of um cancer or intra epithelial neo plays er of

the vulva vagina or cervix.

There's a link there.

It's one of the most common malignancies in people who

are HIV positive.

There's a connection between anal cancer presentation and cigarette smoking.

And interestingly a small group of people that might have

undergone organ transplantation uh and been immuno suppressed.

There's a connection and a slight increased number in that

population there, the most likely sexually transmittable agent implicated HPV

and presence of HPV.

So being HPV positive or not doesn't seem to influence

survival. We think it's type 16 And type 18 and

33 have got an association with anal cancer but that's

based on limited evidence.

And about 90% of anal cancers in the UK is

now thought to be linked to HPV infection.

Um about 91% of anal cancers in women and 75%

in men um present in people who are HPV positive

and we think that there is a risk perhaps or

an association between sexual behavior um including but not limited

to anal intercourse but also um numbers of partners.

So actually transmitted diseases there's a little bit more of

information that can be found on the link below.

So you will have studied or come across HPV in

relation to some guy any cancers, won't you?

Right then thinking about the area of the body that

we're talking about the function that it performs.

Can you list any possible signs and symptoms that you

might expect to be logically associated with an anal cancer?

You pause the video now.

Okay so you may well have come up with a

couple of these points, bleeding is a common symptom, pain,

discomfort and itching lumps.

Which are quite often confused with hemorrhoids or piles, mucous

discharge. Also type presentations.

Um some late stage disease.

You might see difficulty with fecal continents and might see

some leakage.

But interestingly about one in five of people with an

anal cancer don't have any symptoms at all.

A couple of different specific symptoms associated with where the

cancer might present.

So you are presenting in the anal canal.

You've got very non specific symptoms really.

You might have some bleeding discharge discomfort.

Been reporting about half of cases.

About a quarter of people are aware of some sort

of mass.

Either when they're passing a bowel motion or wiping or

cleaning themselves to us in the peri anal area.

You might see a palpable mass on discharge and sometimes

you find an accidental present.

You pick up a cancer accidentally during a physical examination

and you might pick up an enlarged inguinal node because

as we know from our previous lymph drainage slide that

limb from this region will head towards inguinal nodes.

So sometimes you can pick up high levels of dysplasia

on histological examination of hemorrhoids specimens later stage presentations.

Late stage to US.

You might have a fecal incontinence and that's due to

speak to disruption.

Or you might have fistula formation.

Symptomatic mets.

So metastatic disease that spread beyond the pelvis causing symptoms

are rare in this group.

So what is a fistula?

You've come across this side before in relation to rectal

cancer management is where you've got an abnormal joining and

we could have carla physical Carlo vagina for example.

Yeah. Thinking about those rare uh presentations such as a

malignant melanoma.

You might see an area of pigmented pigmented skin, there's

usually quite firm looks like a bruised hemorrhoid which can

often postpone diagnosis and treatment spread.

So you've mainly you're looking at local invasion, followed by

limp spread, nodal involvement is more common in the US

presented in the canal than those in the Perrier no

or marginal areas and involvement of obviously correlates with depth

of penetration and to exercise and therefore stage of disease,

About 10% of us present with some level of node

involvement but that will increase to around 20 once the

primary is bigger than five cm.

Blood bond spreads less common as we said.

But if that does occur, the main sites to which

that will occur are liver, lungs and bone to a

staging. Then we've got a T.

And M system we've got a descriptor of carcinoma in

situ. Well we've got some cells that have undergone cancerous

changes and they'll be managed in a usually a surgical

way and we've got T.

Stages T 123 and four T.

T. One describes the tur that measures two centimeters or

less. T two is a tur that measures between two

and five.

T. Three is a tumor that's bigger than five and

T. Four can be any tumor size but that it's

growing into surrounding tissues or organs such as urethra, vagina,

bladder structure.

Obviously depending on whether it's in a male or a

female pelvis.

We can also use a staging descriptor of 1-3, 8

b. and four.

So again I'll let you read through those in your

own time, logical in relation to size and whether we've

got spread into nearby structures as well.

So how would we assess disease?

Um Usually under general anesthetic with.

So we can have a thorough examination and take some

biopsies we can inspect.

So we can visit look and visualize the area, inspect

the peri anal skin could perform a.

D. R.

E. A digital rectal examination in females.

We could also perform a vaginal examination so that we

could check for any presence of fistula or evolvement of

posterior vaginal wall.

You can biopsy use a prop to Skopje and sigmoidoscopy

when we want to see how far up the tumor

extent. So in order to define what we call the

upper limit of the tur we can test for HIV

and HPV status and we can obviously perform excision biopsies

of any any lymph nodes using fine needle aspiration if

we need to C.

T. Is used as it is with rectal cancer and

other pelvic disease.

Abdo pelvis.

So we can check for spread.

Look for any presentation of metastatic disease beyond the pelvis.

MRI will give us a good detailed picture of what's

happening. We can pet ct we can chest X ray

to see whether we've got any metastatic disease and we

can perform a full range of blood tests to assess

function of other organs again so we can pick up

where there's any metastatic problems.

Okay so treatment logically there is a connection between stage

of disease and treatment management approaches that we can offer.

So for this carcinoma in situ this almost sort of

pre cancerous state.

We can have some surgery which will be performed to

just remove the affected area of meta play asia.

Um for stage one and 2.

So you are less than a cent to me to

have local resection possibly back in therapy.

Um Anything bigger than a centimeter or where there's involvement

of the anal sphincter.

Then we're looking at offering chemo radiation.

So three a.

We've got the approach of chemo radiation and surgery to

remove any remaining cells or for any lymph nodes.

Stage four.

We've got chemo radiation surgery in a combination and we

want to control disease and any symptoms as far as

possible. So anal cancer management you will generally see patients

being treated for anal cancer with chemo radiotherapy.

Usually external beam with radical surgery been reserved for the

management of recurrent cancer for epidermal cancers of the anal

cancer of the anal canal.

Sorry. So where we've got epidermal owed to us.

That's the approach that we take that allows preservation of

function. And the reason we want to preserve this function

is why why is it important to maintain sync to

function? Well, obviously stink to function is associated with continents.

And if we treat in such a way as to

impair that function then we're obviously going to have to

look and explore with the patient the possibility of a

permanent stoma.

So a little bit of history, there's a number of

different trials and when you start to look at different

research papers you'll see that evidence and the regime that

we use now.

So the dose fraction ation chemo agents have evolved and

come from a long line of historical trials Such as

Act two at 1 accord the artichoke trial.

And we're still at the point now where we're trying

to decide whether there's anything better than what we've currently

been using.

Um And that's the approach of chemo radiotherapy with five

F. You and my to my cincy there's a couple

of different references here for you.

So if you wanted to explore the trials that have

happened in the past, you can pick these up quite

easily on the uni library website by just cutting and

pasting these into that and you'll see.

So although it's a small number of patients that are

obviously diagnosed with anal cancer each year it is a

site that's quite highly researched and we definitely are constantly

striving to improve outcomes um improve outcomes not just in

terms of survival but also thinking about the acute and

late effects and quality of life issues associated with different

management approaches.

So combined modality treatments of chemo radiation is a standard

of care for squamous cell carcinomas.

We don't have a nice guidance for anal cancers Until

the 70s.

What tended to happen was an abdominal perennial reception.

So that huge upper open surgery to remove tur and

bowel itself.

And then since then we've got evidence from a number

of different studies that confirm that this combined modality treatment

achieves a complete response in about 80-90% of patients.

So it's effective.

We don't see an overall survival advantage but we do

definitely see an improvement in local control.

And importantly this colostomy free survival compared with just giving

radio therapy by itself induction chemo or radiation dose intensification

doesn't tend to improve colostomy free survival.

That's what we've got data for at the minute.

But we have got a trial, ongoing where and further

evidence may may or may not support that.

So surgery then a pr is reserved for salvage.

So you try to do all the things first and

then use that as a last resort.

Although complete response rates are lower in patients with a

large tur most patients can be spared colostomy and the

overall survival is good.

Some patients with fecal incontinence artificial when they present might

need a pre treatment colostomy.

So a diversion which can then hopefully if treatment successful

can be reversed at a later date, patients who are

HIV positive then there's a number of different policies that

come into play here and within your own centers, you'll

have your own policies and work instructions associated with how

to manage a patient who is HIV positive and make

sure that you keeping a close eye on any acute

effects that they might be experiencing from the treatment.

The treatment is obviously influenced by the presence and severity

of other illnesses that might or might not be affecting

them. And and it's I guess it's a a case

of working closely with the team who are managing the

patient's HIV um and making sure that again, you observe

them and that you are closely watching and looking out

for any sort of toxicity that might present.

So local symptoms and loss of an erectile control might

mean that you need to treat the anal canal.

You've got to select the patient carefully and weigh up

treatment options and associated toxicity radical surgery can be reserved

for symptomatic or persistent local cancer that's affected continents.

There are a couple of different papers in the resource

folder for you to read in relation to how best

to manage a patient who's HIV positive.

So this combined modality treatment is well established and we've

got some recent randomized trials that have tried to look

at finding what is the ideal combination of chemotherapy agent

that you can throw at this treatment site to try

and get the best results.

So two trials found that five f.

you know flurry uracil and mighty mice in C.

Based chemo radiation results in a significant improvement in disease

free survival and overall survival compared with if you use

a five F.

U. And CISplatin.

And a trial called accord three found that some induction

chemo or Bracke boost to a standard chemo XRT regime

showed no advantage in colostomy free survival.

Um So radiotherapy and chemotherapy agents of fleury uracil or

five F.

You when mighty mice in C.

Is kind of the standard of care that you'll see

out in practice today I.

M. R.

T. Has become standard technique because it has the potential

to boost dose and lower acute and long term toxicity.

Um There are some guidance that clinicians and especially videographers

and yourselves can refer to that describe the approach that

should be taken for I.

M. R.

T. In anal cancer.

And again I've made a link available to those.

So here is some more references if you wanted to

do some further reading radiotherapy technique wise then you'll be

able to recall from your own practice what kind of

dose and over how many fractions a treatment is given.

And you'll see descriptions like this relating to stages.

So we've got 50.4 and 28 to the anus to

evolve nodes and to elective nodes and then T.

Three T.

Four disease.

We're delivering this dose and this fraction ation when you

have your session with lucy.

Um the specialist Ray Geographer she will review that with

you as well.

So we've got non I.

M. R.

T. Or conf formal techniques that use a phased approach

and deliver the doses described here.

So plato three is a trial that's looking at a

dose escalation and I've made a link as well in

the resource folder to another trial that's ongoing.

So unfortunately about 30% of patients develop what's called advanced

disease that can't be treated surgically.

And um there is some recent evidence that shown that

a chemo agent called carbon platinum and one called um

paclitaxel should be the first line treatment here.

And there's some future work looking at exploring immunotherapy and

obviously we're expecting and anticipating and hoping for a positive

impact of the HPV vaccination program and potentially looking and

hoping for reduced anal cancer numbers in the future.

Yeah so chemo radiotherapy is the treatment of choice because

it enables successful treatment with positive outcomes and this maintenance

of a function so that we can avoid a permanent

colostomy um surgery wise we have a couple of different

approaches available.

We've got abdominal perennial excision with reconstruction.

Um, and there is a paper in my resource folder

and some more information on surgical approaches for this area

of the body.

So we know that there's a correlation between stage and

survival rates.

We can choose and pick out and put a lens

on. Where are you presents and the prognosis associated with

that site.

So you are presenting in the anal canal.

Looking at five year survival rates of about 65%.

Um local control with preservation of anal function.

When we use radiotherapy and chemotherapy.

Looking about 75%.

Numbers change slightly in the peri anal area.

We've got rates at about 80% on local control with

about 85%.

There are no UK wide statistics available for anal cancer

survival by stage.

These are the latest figures that I can find.

Um But again, numbers are small numbers of presenting, you

know, tumors a small per year.

And the statistics and non age standardized, standardized, which means

that they don't take into consideration the age of the

people. But this is what we're looking at here at

the stage 123 and four Overall.

About 85% of people survive their cancer for a year

or more.

That was 65 and about 15 um for 10 survival

as you would imagine, is strongly related to stage and

we've got good survival outcomes for those early stage diseases

and far more worse and poor survival outcomes for people

with the latest stage presentations.

And there's a couple of graphs here to show you

female and male survival, the number of people overall as

well and stage, a definite correlation between stage and survival

rates. I want you to think now about patient care

and can you list any potential treatment related side effects,

both acute and long term that you might expect to

see with patients presented with an anal cancer who are

receiving chemo radiotherapy under your care.

So you may well have come up with a couple

of these or maybe all of them are and maybe

more. We've got potential treatment related side effects affecting bowel

function. We might see blood, we might see itching pain,

urinary symptoms.

Skin is the main presenting acute toxic side effect that

we'll see with this particular treatment and I'm sure you'll

have come across patients receiving Chemo XRT for nail cancer,

who've got a significant and severe skin reaction.

That requires a lot of input from the treating team

to manage effectively and ensure that this patient can get

through the treatment course, you would hope that with the

increased use of smart that that incidents of Horrendous skin

reactions will will have reduced and will be much better

than certainly the types of skin reactions that I saw

10 years ago in patients who had come con formal

treatment for people who are premenopausal, the doses that we

give in to this area, the body, we've got to

be mindful and consider and make sure the patients fully

aware of issues relating to sterility.

Both men and women menopause in women, obviously vaginal stenosis

and dryness and there's all the associated psycho sexual issues

um that we need to think about in this area

of the body.

So just take a second now to think about how

side effects are managed in your center.

So you may recall particular patients presenting with this uh

tur and the management approaches that were taken but just

to pick up on some of the potential key issues

that you might have to be mindful of um skin

reactions that can be brisk and extremely painful.

So they need to be carefully managed through whatever protocols

you've got available to you in your center that might

be through a combination of analgesics, pain relief and a

quiz on topical agents or dressings potentially or a combination

um diet.

Obviously when we have a situation where we're trying to

balance and manage the effects of radiotherapy and chemo on

somebody's bowel function, then we've got appropriate management that we

can offer in relation to diet information and also some

agents that could be used such as the pyramids or

fiber gel for example.

Um The reaction itself, the acute reaction is usually vastly

improved around six weeks after treatment is completed.

But having said that it is a tough regime, I

think for people, I've got a couple of slides here

now with some old exam papers.

So if you would like to in your own time,

have a go with those.

And what I'll do is I'll post some expected answers

to help you.

As always.

If you have any questions at any point in time,

anything that you need some more help with or don't

understand them, please just email me and get in touch.

Okay? Thanks for your time.

Bye bye.

Anal Cancer Management

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