Watch and Wait as Treatment for Patients With Rectal Cancer (WoW)

A Multicenter Prospective National Cohort Study for Patients With Advanced Rectal Cancer - is it Possible to Induce Remission and Avoid Surgery - Watch and Wait?

A national cohort study with all patients scheduled for neoadjuvant treatment with (chemo)radiotherapy or short course radiotherapy with delayed surgery 6-8 weeks) for rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI (and patients that have been offered short course raditotherapy with delayed surgery due to various reasons). The tumours are positioned midrectal or low and are palpable with the finger. The patients offered this treatment after recommendations on their local multidisciplinary tumour board will be will be informed and offered to participate in the study. Patients scheduled for short course radiotherapy with immediate surgery cannot be included.

Study Overview

• Status: Recruiting
• Conditions: Rectal Neoplasms
• Intervention / Treatment: Device: MRI; Procedure: endoscopy; Procedure: Surgery

Detailed Description

• Biopsies and blood from patients with rectal cancer subject to neoadjuvant treatment with (chemo)radiotherapy or radiotherapy 5x5 Gy with at least 6-8 weeks wait until surgery. All patients will be asked to answer a QoL questionnaire (appendix C) to cover their experiences of the neaodajvuant treatment. (Answered at diagnosis and at evaluation of treatment and decision of surgery or inclusion in the Watch and Wait part of the study).

All patients will undergo scheduled (chemo)radiotherapy according to national guidelines. The patients with chemoradiotherapy will be evaluated at 8-10 weeks after completed treatment (25) with pelvic MRI. After this evaluation at 8-10 weeks patients with suspected complete response or near complete response will examined according to the protocol below.

All patients that are considered to have complete response will be offered a "Watch and wait" approach with follow-up according to the protocol. They will then be followed at one of the Regional University Hospitals within their catchment are.

All patients with a palpable rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI (and patients that have been offered short course raditotherapy with delayed surgery due to various reasons) that does not achieve complete response will serve as control and will be treated with surgery as planned prior to initiation of (chemo)radiotherapy.

Patients with indication of complete response on follow-up MRI will undergo endoscopy, and digital rectal examination to ascertain complete response. MRI together with documentation from endoscopy will be reviewed at the Regional University Hospital to extablish agreement regarding interpretation. All the below mentioned criteria must be fullfilled to be considered complete response:

1. No suspicious metastatic lymph nodes or evidence of remaining tumour on MRI. In the majority of cases a complete response on MRI will be seen as areas of homogeneous fibrosis. Absence of any remaining pathological tissue is seen in a minority of cases.
2. Endoscopic examination with light/white mucosa or scar, telangiectasies. Prescence of fibrosis and oedema.
3. No palpable tumour on clinical examination (26).

In the spring of 2023 200 pts included. An amendment was sent to the ethical review board to enable continued inclusion while the initial 200 pts are analyzed. This has been approved and the study has thus planned continuation for another 2-3 years.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eva Angenete, M.D., Ph.D.; Email: eva.angenete@vgregion.se

Study Locations

• Sweden
  • Gothenburg, Sweden, SE 416 85
    • Recruiting
    • Dept. of Surgery, Sahlgrenska University Hospital/Ostra
    • Contact: Eva Angenete, MD,PhD; Phone Number: +46313438410; Email: eva.angenete@vgregion.se
  • Stockholm, Sweden
    • Recruiting
    • Karolinska Institutet
    • Contact: Anna Martling, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All patients in Sweden with a palpable rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI considered appropriate for 5x5 Gy and 6-8 weeks of wait prior to surgery according to Stockholm III (28) or a palpable rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI a planned schedule for CRT according to the Swedish National Program for rectal cancer scheduled for neoadjuvant therapy are possible to include.

The study includes two parts, where part one is optional in including hospitals. The aim of the biopsy substudy 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.

For the WoW part of the study all patients that achieve complete response after neoadjuvant treatment according to the specified criteria above can be included in the Watch and Wait protocol. In detail this includes patients with:

Midrectal or low rectal cancers that are palpable and considered with an indication of 5x5 Gy and long wait (6-8 weeks) (the indication for waiting may be logistics, co-morbidity, advanced age):

• cT4bNX
• anycTanycN and cMRF+ anycTanycN and lateral lymph nodes on MRI

Exclusion Criteria:

• No informed consent received for participation.
• Patients with rectal cancer that is scheduled for (chemo) radiotherapy but is not palpable during rectal examination (10-15 cm) as this cannot be examined by digital examination and followed as scheduled.
• Contraindication for MRI such as presence of non compatible metallic implants or claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No surgery; Patients with indication of complete response on follow-up MRI will undergo endoscopy, and digital rectal examination to ascertain complete response. MRI together with documentation from endoscopy will be reviewed at the Regional University Hospital to establish agreement regarding interpretation.	Device: MRI; Procedure: endoscopy; Continuous follow-up. All patients with complete response will be followed for ten years. Details from the follow-up schedule will be registered in clinical record forms including information on the endoscopic findings, MRI findings and digital examination. They will be followed ever third month for the first two years as follows: PET-CT is optional, but can be performed at inclusion; Pelvic MRI including diffusion weighted imaging according to appendix C.; Clinical examination; Endoscopy (flexible sigmoidoskopy) with photodocumentation; CEA After two years the patients will be followed every six month with: Pelvic MRI including diffusion weighted imaging according to appendix as at baseline; Clinical examination; Endoscopy with photodocumentation; CEA
Active Comparator: Surgery; Patients with indication of complete response on follow-up MRI will undergo endoscopy, and digital rectal examination to ascertain complete response. MRI together with documentation from endoscopy will be reviewed at the Regional University Hospital to establish agreement regarding interpretation. Patients with complete response will be offered watch and wait strategy, but the patients that want surgery will be operated according to the multi disciplinary conference decision.	Device: MRI; Procedure: Surgery; Surgery according to recommendations from the multidisciplinary group in patients that prefer surgery to a watch and wait strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year disease free survival.	Thus this includes patients that have had regrowth and been operated for their tumour. Includes metastastic surgery as well	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage re-growth during follow-up	Endoscopic or MRI indication of regrowth	10 years
Local recurrence after salvage surgery due to regrowth	Local recurrence as shown by MRI, endoscopy or digital examination	10 years
Results after surgery for re-growth	Complications and mortality after surgery	10 years
Long-term survival	Overall survival	10 years
Number of patients with no response, partial response and complete response.	Number of patients in each group - no response, partial response and complete response	Accrual period - probably 4 years
Anorectal function measured by LARS score	Anorectal function measured by LARS and then compared to patients operated.	5 years
Quality of life measured by a clinometric approach	QoL measurments sent to patients	up to 24 months
Health economic evaluation	A cost efficiency analysis	5 years

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Eva Angenete, M.D., Ph.D., Sahlgrenska Academy at Gothenburg University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: chemotherapy; radiotherapy; complete response
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: WoW

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No