Watch and wait: Clinical complete response after (chemo)radiotherapy in advanced rectal cancer: A multicentre prospective national cohort study (WoW)

 

The hypothesis

It is possible to avoid surgery in a selected group of patients (palpable low and mid rectal tumours) with complete response after neoadjuvant (chemo)radiotherapy for rectal cancer with similar or better oncologic outcome at three years as compared with patients without complete response treated with surgery?

Endpoints

Primary:

  • 3-year disease free survival. Thus, this includes patients that have had regrowth and been operated for their tumour. Patients that have had metastastic surgery are included as well.

Secondary:

  • Percentage of re-growth during follow-up (10 years).
  • Local recurrence after salvage surgery due to regrowth.
  • Results after surgery for re-growth.
  • Long-term survival.
  • Number of patients with no response, partial response and complete response according to MRI and pathology, this will include patients with biopsies at selected centers as well as using the Swedish ColoRectal Cancer Registry.
  • Anorectal function measured by LARS score(24) and other questions in QoL questionnaires.
  • HRQoL 0, 6, 12, 24 months.
  • Health economic evaluation.
  • Endpoints for a substudy:
    • Identifying biomarkers for complete response.
    • Identifying biomarkers for normal tissue damage.

Inclusion/exclusion

Inclusion criteria:

For the WoW part of the study all patients with rectal cancer that achieve complete response after neoadjuvant treatment evaluated at 6 weeks, 12 or 16 weeks (if signs of near complete response are present at first or second evaluation) according to the specified criteria above can be included in the Watch and Wait protocol. In detail this includes patients with:

  • Patients with rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI and planned schedule for chemoradiotherapy according to the Swedish National Program for rectal cancer scheduled for neoadjuvant therapy are possible to include.
  • Patients with rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI or anycTanycN considered appropriate for 5x5 Gy and 6-8 weeks of wait prior to surgery according to Stockholm III (29). (the indication for this regime according to Stockholm III could be logistics, co-morbidity and advanced age) 

In the biopsy substudy the aim is to identify tumour and plasma markers for complete response, thus all patients that will receive (chemo)radiotherapy in the neoadjuvant setting are included to provide a control for the biopsies.

Patients not willing to participate will be treated according to local and national guidelines but will be offered to answer the same QoL questionnaires.

Patients will be included by the treating surgeon. Patients receive information and sign informed consent.

As soon as a patient has given informed consent this is communicated by phone to the secretariat at SSORG at a specific phone number, and then the treating surgeon receives a study number for the patient that will enable registration in the web-CRF without further identification.

Patients with complete response but with metastases where the clinician chooses to follow the patient according to the algorithm in the study are not formally included in the study but will be registered.

Exclusion criteria:

  • No informed consent received for participation.
  • Contraindication for MRI such as presence of non-compatible metallic implants or claustrophobia.

Inclusion of patients:

Aiming at including 200 patients.

Documents

Protocol (click on name to view/download): WoW

Contact

Principal investigator:

Eva Angenete

Deputy principal investigator:

Anna Martling

Questions:

PI Eva Angenete (eva.angenete@gu.se) or research nurse Jane Heath (jane.heath@vgregion.se)