Editing Rectal cancer (section)

== '''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'''