Editing Rectal cancer


== '''Epidemiology''' ==

* Increasing incidence in young     patients

== '''Anatomy/pathophysiology''' ==

* See colon cancer topic for     pathophysiology
* Rectum starts ANATOMICALLY     where the three taenia coli fuse into a single longitudinal smooth muscle     coat (rectosigmoid junction). However, oncologically, we refer to any     cancer that develops in the extraperitoneal large bowel as rectal cancer.
* Much higher risk of local     recurrence than colon cancer
* More likely to metastasise to     lungs than colon cancer, due to venous drainage into systemic circulation

== '''Pre-op work-up''' ==

* Ultimate goal is to stage the     disease and identify most appropriate treatment in a timely manner.
* Hx/exam
** Change in bowel habit,      incontinence, previous colonoscopies, FHx
** Stomal therapist
** DRE and proctosigmoidoscopy
*** Orientation       (anterior/lateral/posterior, rather than o'clock), circumferential       involvement including rectovaginal septum, extent of proximal       involvement, size, degree of fixation, location of disease related to       proximal extent of anorectal ring
*** Sphincter tone
* Routine bloods and CEA
* Imaging
** ''Delineate      depth of penetration, assess local nodes, determine presence/absence of      mets''
** Pelvic MRI usually without      contrast unless suspicion of fistula
*** MRI best for       differentiating between T2 and T3, and also very good at distinguishing       T3 from T4.
*** MRI prone to over-staging       early disease.
*** T2 phase: inner       hyperintense layer is mucosa and submucosa, hypointense middle layer       represents muscularis propria; hyperintense outer layer represents       perirectal fat. Sometimes hard to see the border between submucosa and       muscularis propria; hence not as good for differentiating T1 from T2.
*** Better at lymph node       involvement and circumferential margin than USS
*** DWI is useful for       evaluating locoregional nodes - if it's bright on DWI, means it's a       cellular tumour. Also needs to be low on ADC to confirm.
** Endoscopic rectal USS
*** USS can differentiate       between T1 and T2 much better than MRI
*** Operator-dependent
*** Not as good at identifying       lymph nodes
** CT CAP (CXR insufficient)
*** To look for mets
** PET - mixed data on utility
*** MAYBE helps to pick up       distant mets - or maybe further workup of ?met found on CT
*** Only really recommended       currently for patients with equivocal imaging for mets
* Colonoscopy
** Measure distance using rigid      sig - flexible is notoriously inaccurate
** Need full scope due to 4%      risk of synchronous cancer and 10-20% risk of synchronous polyp


== '''Staging''' ==

* Use TNM 8th edition - same as     colon cancer, but note that T3 is mesorectal
* Regional: mesorectal, lateral     sacral, presacral, inferior and superior rectal, inferior mesenteric
* Metastatic: external and     common iliac, inguinal

= '''Management options''' =

* Local excision
* Radical resection +/-     adjuvant therapy
* Neoadjuvant chemoradiotherapy
** Subsequent surgery
** Subsequent watch and wait
* Palliation

== '''Management by stage''' ==

* Stage 1:
** cT1N0 (lymph node met risk      3-15%) and absence of high-risk features OR T2N0 and unfit for surgery:      local excision
*** If clear margins then can       probably just have surveillance
*** High-risk features - see       box below
** T2N0 or T1N0 with high-risk      features: sphincter-sparing surgery (LAR or APR) with TME. Most patients      don't need neoadjuvant CTX.
* Stage 2 (T3-T4N0M0):     neoadjuvant CTX, LAR/APR+TME, and probably adjuvant CTX.
* Stage 3 (TxN1M0): neoadjuvant     and adjuvant CTX + LAR/APR
* Stage 4 depends on     resectability of mets and QoL considerations



== '''Surgery''' ==

* '''Principles'''
** Circumferential Resection      Margin
*** Refers to adequacy of       radial resection margin
*** Needs to be >2mm
** Distal Resection Margin
*** Strive for at least 2cm,       but 1cm is acceptable in the absence of adverse histologic features, or       need to preserve sphincter
*** Frozen section can help       establish this
*** Distal spread occurs in       1-2% of cases with a 2cm margin
** TME
***
*** Total mesorectal excision -       complete resection of visceral mesorectum with pelvic nerve       preservation. This is achieved by resecting along the embryological       mesorectal envelope, which theoretically should contain the cancer.
*** Refers to sharp dissection       in the TME plane/'holy plane', to also take connective tissue from       around rectum
*** Starts at level where       rectum becomes extra-peritoneal, and either goes all the way down or       stops 5cm distal to tumour
*** Boundaries:
**** Anteriorly: plane between        mesorectal fascia and Denonvillier's fascia
**** Posteriorly: plane between        mesorectal fascia and presacral fascia
**** Laterally: follow a line        connecting the anterior and posterior dissections. There are no        relevant ligamentous structures that will be identifiable, but look out        for vessels (and inferior hypogastric plexus, which is closely related        to the lateral margin of TME, and needs to be preserved to avoid        bladder or sexual dysfunction)
**** Inferior: where levator        ani merges with the deep part of the external sphincter
*** Increases overall survival
*** Decreases local recurrence       rate from 20% to <10%
*** Less risk of urinary       incontinence/damage to sphincter complex if you stay in the TME plane
*** Lateral pelvic lymph nodes       - controversy regarding best approach. Risk of spread to here increases       with lower tumour height and increased T category. Therefore, if       suspicious nodes are seen, particularly in the internal iliac chain,       they should be seen as potentially resectable elements of locoregional       disease.
*** If there is breach of       mesorectal fascia by tumour, attempt to resect all involved structures.       Theoretically this should have led to neoadjuvant radiotherapy if       identified pre-op.
** Transanal TME (TaTME)
*** Required due to the       difficulty in performing distal TMEs due to the bony angulation of the       pelvis
*** First described 2009 - far       from universal adoption at this point.
**** Patient in lithotomy
**** Can be done as two-team        approach - simultaneously doing bottom-up and top-down approaches to        improve operative time
**** Best for patients with        locally advanced cancers in distal third of rectum
**** Difficult in mid-rectum,        impossible in upper rectum
*** 10% risk of ureteric       injury, 17% get presacral abscess
* '''Local     excision procedures'''
**
** ''Transanal      excision (TAE)''
*** Limit usually 6-8cm
*** Lithotomy or prone       jack-knife with self-retaining retractor
*** 1cm margin, full-thickness       excision to peri-rectal fat
*** Close defect with suturing
*** Check anal canal for       narrowing
*** Complications:
**** Bleeding
**** Infection
**** Retention
** ''Transanal      endoscopic microsurgery (TEM)''
** ''Transanal      minimally invasive surgery (TAMIS)''
*** Mid to upper rectal lesions
*** 40mm endoscope and long       endoscopic operating equipment
*** Carbon dioxide insufflation
*** Full-thickness excision
*** Close defect
** '''Advantages'''
*** Significantly lower       morbidity (fewer stomas, better QoL short-term)
*** Less invasive
** '''Disadvantages'''
*** May need to have radical       resection anyway
**** If pathology reveals        high-risk features, or more invasion than was thought.
**** If recurrence occurs        (salvage procedure - tend to fare worse than those that had the radical        resection straight-up - maybe because didn't sample nodes, and they        would've got adjuvant CTX if nodes were detected)
*** Difficult to perform       >8cm from anal verge technically (although TAMIS can go 15cm)
*** Can't do full oncologic       staging
*** Higher risk of local       recurrence (11-29%)
*** Full resection not always       possible down the track
*** Needs closer surveillance
* '''Radical     resections'''
** Sphincter-preserving (need      cT2-T4 disease, ability for adequate distal margin, and good premorbid      sphincter function)
*** '''Low       anterior resection (LAR)'''
**** Contraindications:
***** Tumour <1cm from upper         portion of anorectal ring, impaired sphincter function (leads to poor         post-op bowel function
**** Reconstruction options        after LAR
***** Straight coloanal         anastomosis
****** End to          end
****** Side to          end
***** Colonic reservoir
****** Seems          to improve short-term function more than long-term
****** No          really strong reason to do it, but consensus seems to be that you do          it if the anatomy is favourable
****** J pouch
****** Transverse          coloplasty pouch
** Temporary diversion after      LAR
*** Consider in patients with       high risk for leak
**** <6cm from anal verge
**** Pre-op RTx
**** Adverse intra-op events
*** Reverse 3/12 post-op unless       waiting for CTX to finish
*** Enema study prior to       reversal to ensure no leak
** Non-sphincter preserving
*** '''Abdominoperineal       resection (APR) aka Miles procedure'''
**** Combined abdominal and        perineal approach to resecting rectum, mesorectum, anus, surrounding        perineal soft tissue, and pelvic floor musculature
**** Permanent end colostomy
**** Indications:
***** Tumour directly involves         sphincter muscles
***** Adequate margins can't be         obtained during LAR (essentially at the dentate line or just above it)
***** Patient already has poor         sphincter function (end colostomy offers better QoL than an         ultra-distal colo-anal anastomosis that could further compromise         continence)
**** Preferred in situations in        which a margin-negative resection would result in loss of anal        sphincter function leading to faecal incontinence
**** Higher recurrence rates        (33% higher) compared to LAR - higher risk of specimen perforation and        positive circumferential margins

== '''Adjuvant CTX''' ==

* Typically 4/12
* Start within 8/52 of surgery
* Has been recent move to shift     all CTX and RTX to pre-op (TNT), which is associated with lower toxicity     and higher treatment completion rates
** ?overtreatment due to      imprecise clinical staging
** ?disease progression in      those who do not respond to CTX
* See discussion under colon     cancer for more

== '''Neoadjuvant chemoradiotherapy''' ==

=== '''Indications''' ===

** Definite
*** T3 and T4
** Relative
*** N1 in cT1/T2 disease
*** Invades or threatens to       invade the mesorectal fascia
** Controversial
*** T1N0/T2N0 with intention of       converting from APR to LAR
* Rationale
** Downstage primary cancers -      increasing the chance of sphincter-sparing surgery, and improving      functional results (based on data for T3 and T4 patients from 2004)

=== Treatment options ===

** Long course      chemoradiotherapy (LC-CRT)
*** Indicated for T1/2N0       disease
*** Chemotherapy just given as       a radiosensitiser - fluoropyrimidines or capecitabine on days of       radiotherapy
*** 50.4-54 Gy total,       administered over 28-31 daily fractions
*** Aim to operate either 6-10       weeks afterwards or >6 months afterwards - initial oedema makes it       hard, then fibrosis makes it hard, then that settles
** Short-course radiotherapy
*** 25 Grays (5 days of 5),       then wait another week, then operate
*** Comparable to long-course       with local recurrence DFS, distal recurrence, OS and toxicity
*** More long-term side effects       than surgery alone
*** Not favoured, not usually       done unless in special circumstances (won't tolerate full course,       synchronous metastatic lesions to minimise delays)
** Neoadjuvant immunotherapy
*** Option for patients with       dMMR cancer
*** Immunotherapy then re-stage
*** No CTX or CRT unless       progression/no response
** Total neoadjuvant therapy      for locally advanced tumours (TNT)
*** Indications: T4, N2,       <5cm from anal verge, threatened mesorectal margin, extramural venous       invasion
*** Need an adequate       performance status, more so than for CRT alone
*** Neoadjuvant       oxaliplatin-based chemotherapy for 12-16 weeks (FOLFIRINOX, FOLFOX or       CAPOX) plus radiotherapy (usually long-course radiotherapy and       capecitabine)
**** FOLFIRINOX has the best        outcomes but also the most toxic
*** Usually start with       chemotherapy, although the optimal sequencing has not been established
*** This has been shown to       significantly improve pathological complete response rate from about 14%       with long-course CRT to about 28% with TNT (RAPIDO and PRODIGE 23       trials)
** Neoadjuvant chemotherapy +      selective use of CRT
*** T2N1, T3N0, T3N1 and       eligible for sphincter-sparing surgery
*** The favoured modern       approach - start off with systemic therapy for three months, then       restage and give RTX if no/minimal response
*** CAPOX and FOLFOX can be       used if the patient has lower performance status; FOLFIRINOX can be used       if the patient has better performance status.
**** '''The        difference between this and TNT is that here you aren't committed to        CRT - restage after CTX, and if good response, go straight to operation'''
**

=== '''Restaging     outcome''' ===

** '''Proceed to      surgery (incomplete response)'''
*** Use tumour regression grade       to describe the primary response to neoadjuvant therapy:
**** 0: complete response
**** 3: no regression
** '''Watch and      wait (complete clinical response to chemoradiotherapy)'''
*** CCR (based on imaging,       endoscopy and clinical findings) occurs in about 20% of patients       following long-course neoadjuvant chemoradiotherapy in locoregionally       advanced mid-to-distal rectal cancer
**** 28% complete pathological        response in RAPIDO trial 2013
*** When compared to a cohort       who then underwent surgery, no difference in local or systemic       recurrence
*** Surveillance can       incorporate following:
**** DRE exam
**** Endoscopic exam +/- biopsy
**** CT
**** EUS
**** MRI
*** Local failures seem to be       about 25% (often salvageable) and systemic failure rates about 8%,       however mature long-term survival data is not yet available
*** Favour watch and wait in       high-risk or comorbid patients, especially those who had TNT, although       this is not standard of care
*** Watch and wait should be       reserved for patients who:
**** Are able to commit to        high-intensity surveillance
**** Acknowledge and accept a        25% local failure, and 8% unsalvageable failure
**** Still prefer organ        preservation over surgery
*** Most units in Australia       still preferring surgery for many patients in this group
*** Very difficult to do a       proper RCT comparing definitive initial surgery with watch-and-wait,       however results are not bad and some prospective trials are ongoing
** '''Treatment      progression'''


== '''Palliation''' ==

* Stents generally avoided -     causes intolerable pain if migrates

== Complications ==

* Obstruction
** Actually rare - the wider      diameter of the rectum and the more obvious symptoms mean it is usually      diagnosed earlier
** If surgery is required,      diverting sigmoid colostomy then neoadjuvant CRT
** Remember to biopsy the      tumour during the operation

[[Category:Colorectal]]