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Complete response to chemoradiotherapy in rectal cancer

Pelican hosted two expert meetings to discuss Watch and Wait for rectal cancer in 2017. At both meetings there were presentations on the information and consent that patients entered into Watch and Wait may ask. These questions and answers below are based on one of these talks.

• Am I missing an opportunity for a better result if I defer surgery in the hope of sustained cCR?
The majority of patients entered into a Watch and Wait protocol with a cCR were originally expected to have surgery. Patients may enter a Watch and Wait protocol if their tumour has regressed (shrunk). If the tumour does not regrow, there may be the opportunity to avoid surgery, preserve the rectum and retain better bowel function. Whilst clinicians at the Pelican meetings were positive about deferring surgery, the research evidence is controversial; studies are mostly retrospective cohort studies and there remains uncertainty amongst some clinicians about this treatment option.

• Am I more likely to suffer metastatic disease if I adopt Watch and Wait, rather than excision?
Patients with Stage II or III rectal cancer have up to a 35% risk of developing metastases 13. In the studies presented at the meetings, the metastatic rate for patients with a cCR varied, with an average metastatic rate of approximately 8% (unpublished data).

• Do a reasonable number of colorectal surgeons in the UK agree with Watch and Wait?
These two meetings brought together more than 100 clinicians and presented data from the Christie Hospital in Manchester, which included data from four hospitals in the UK who followed up patients with a cCR. In 2007 and 2013, questionnaires were sent out to surgeons in England, 122 and 138 surgeons replied and there was a shift in the six year period, with the more recent survey reporting that 64% said they would discuss Watch and Wait management for rectal cancer with their patients14, 15.

• Does cCR equate to my nodes being clear?
Absolute certainty that the nodes are clear can only be achieved by pathological assessment, which requires an operation. However, radiological imaging features can be used to diagnose and monitor suspicious nodes.

• If I get regrowth post-CRT, what is my chance of cure, compared with a recurrence after surgery?
This is a different concept to recurrence after surgery since no tumour has been removed, and is therefore referred to as a regrowth. The majority of patients who have a regrowth can have salvage surgery12. This has been shown by centres in Brazil, Holland, USA, Denmark and UK with patients having good outcomes in terms of disease-free survival.

• What is the chance of a local relapse with Watch and Wait?
Between 20 to 38% of patients who have a cCR and join a Watch and Wait protocol have a regrowth compared to <10% recurrence after surgery. However the prognosis is completely different between the two as a regrowth can still have successful salvage surgery.

• Am I trading life expectancy to avoid a permanent stoma? How much life expectancy?
There does not appear to be a trade-off in life expectancy and, in fact, good or complete response is a marker of good prognosis.

• Do many patients in the UK accept the risk of Watch and Wait?
This is increasingly common. In the published literature, 129 patients from north-west England5 and 6 patients from Exeter16 have avoided surgery and been followed up with a Watch and Wait protocol. But many more patients with a cCR from individual centres are avoiding surgery.

• Will the follow-up needed for Watch and Wait be different from that after post-CRT resection? In what way?
Follow-up after surgery varies, but will mostly include an annual CT scan, blood tests and full colonoscopy in varying frequency. Most centres will discharge patients after 5 years if that patient is disease free. In Watch and Wait, more frequent follow-ups are recommended and includes MRI scan with more frequent endoscopy.

• Am I more likely to need secondary chemotherapy after Watch and Wait, compared with timely resection?
There is no evidence that adjuvant chemotherapy has any benefit in patients managed under a Watch and Wait programme. Some centres will give additional chemotherapy to some patients, but this is not standardised.

• If I do not respond to CRT, would you recognise my non-response?
Patients who do not have a cCR will go on to have surgery.

• If not, would I be disadvantaged by delaying definitive surgery?
The published data and results of these two meetings suggest that patients are not disadvantaged by delaying surgery in patients with cCR.

13. Breugom AJ, Swets M, Bosset J-F, Collette L, Sainato A, Cionini L, et al. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data. The Lancet Oncology. 2015;16(2):200-7.
14. Wynn GR, Bhasin N, Macklin CP, George ML. Complete clinical response to neoadjuvant chemoradiotherapy in patients with rectal cancer: opinions of British and Irish specialists. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2010;12(4):327-33.
15. Sao Juliao GP, Smith FM, Macklin CP, George ML, Wynn GR. Opinions have changed on the management of rectal cancer with a complete clinical response to neoadjuvant chemoradiotherapy. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2014;16(5):392-4.
16. Dalton RSJ, Velineni R, Osborne ME, Thomas R, Harries S, Gee AS, et al. A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management? Colorectal Disease. 2012;14(5):567-71.

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