Non-operative Management for Rectal Cancer

(NOM Trial)

Overseen By Selina Schmocker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mount Sinai Hospital, Canada

Must be taking: Chemoradiotherapy

Disqualifiers: Metastatic disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 5 year Phase II study to evaluate the safety of non-operative management (NOM) in patients with low rectal cancer (LRC) who achieve a complete clinical response (cCR) following chemoradiotherapy (CRT). The safety of NOM will be evaluated by assessing (i) rate of local re-growth and (ii) rate of macroscopically positive resection margin (R2) when surgery is required due to local re-growth. NOM will be considered safe or as effective as surgery to achieve local control if the rate of local re-growth is equal to or less than 30% and the rate of a macroscopically positive margin is 0%.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Non-operative management, Watch and Wait, Surveillance with Selective Delayed Surgery for rectal cancer?

Research shows that the 'watch and wait' approach can be effective for some rectal cancer patients who respond well to initial treatments, as it allows for organ preservation and avoids surgery in cases where the cancer does not regrow. However, about 25% of patients may experience local regrowth, and 10% may develop distant metastases, indicating the need for careful monitoring. ^{1 2 3 4 5}

Is the watch-and-wait approach for rectal cancer safe?

The safety of the watch-and-wait approach for rectal cancer is still unclear, as studies have focused more on its effectiveness and outcomes rather than directly on safety. However, it is being increasingly used in selected patients, suggesting some level of acceptance in the medical community. ^{1 2 6 7 8}

How does the 'Watch and Wait' treatment for rectal cancer differ from other treatments?

The 'Watch and Wait' treatment for rectal cancer is unique because it involves closely monitoring patients who have responded well to initial therapy, instead of immediately performing surgery. This approach aims to preserve the rectum and avoid the potential complications and reduced quality of life associated with surgical removal. ^{4 7 9 10 11}

Research Team

Erin Kennedy

Principal Investigator

Sinai Health System

Eligibility Criteria

This trial is for adults over 18 with low rectal cancer who've finished chemoradiotherapy and show no signs of the cancer remaining. It's not for those pregnant, with other cancers in the last 5 years, inflammatory bowel disease, unable to have an MRI, metastatic disease, unfit for surgery or multiple colorectal cancers.

Inclusion Criteria

Provides written consent

I completed standard chemoradiotherapy for stage II or III cancer.

I am scheduled for or likely to have an APR surgery.

Exclusion Criteria

I have had more than one primary colorectal cancer.

My cancer has spread beyond its original location.

You cannot have an MRI scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8-10 weeks

1 visit (in-person)

Chemoradiotherapy

Participants undergo combined chemotherapy and radiotherapy as pre-operative treatment

8-10 weeks

Active Surveillance

Participants undergo active surveillance with regular clinical visits, physical exams, endoscopy, and imaging assessments to monitor for tumour re-growth or spread

2 years

Visits every 3, 6, 9, 12, 18, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after the active surveillance phase

2 years

Treatment Details

Interventions

• Non-operative management

Trial Overview The study tests if patients with a complete response to chemoradiotherapy can safely skip surgery. Over five years, it'll check how often the cancer comes back and if any subsequent surgeries due to regrowth result in clear margins around the tumor.

Participant Groups

Group I: non-operative management Experimental Treatment 1 Intervention

Patients with low rectal cancer who have achieved a complete clinical response following chemoradiotherapy will undergo active follow-up with regular clinical visits, physical exam, endoscopy and imaging assessments at regular intervals for 2 years to assess for tumour re-growth or spread to the liver and lungs

Non-operative management is already approved in European Union, United States for the following indications:

Approved in European Union as Non-operative Management for:

• Locally Advanced Rectal Cancer

Approved in United States as Non-operative Management for:

• Locally Advanced Rectal Cancer

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Recruited

70,700+

Findings from Research

In a study of 444 patients with locally advanced rectal cancer treated by expert colorectal surgeons, the type of neoadjuvant therapy and organ preservation rates varied among surgeons, but did not impact disease-free survival rates.

The findings suggest that differing approaches to the watch-and-wait strategy among expert surgeons do not significantly affect patient survival outcomes, indicating that patient selection for this strategy can be flexible without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoption of Organ Preservation and Surgeon Variability for Patients with Rectal Cancer Does Not Correlate with Worse Survival. Kim, JK., Thompson, H., Jimenez-Rodriguez, RM., et al.[2023]

In a study of 324 patients with locally advanced rectal cancer, a watch-and-wait strategy after total neoadjuvant therapy resulted in organ preservation for about 50% of patients, demonstrating its potential as a viable treatment option.

The three-year disease-free survival rate was 76% for both treatment groups, indicating that this approach does not compromise survival compared to historical treatments involving surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. Garcia-Aguilar, J., Patil, S., Gollub, MJ., et al.[2023]

The watch-and-wait (W&W) approach for older patients with a clinical (near) complete response after neoadjuvant treatment for rectal cancer shows a high local regrowth-free rate of 88% and a non-regrowth disease-free survival rate of 91% over a median follow-up of 37 months, indicating its efficacy as a treatment strategy.

This approach allows most patients to avoid major surgery and colostomy, while maintaining good bowel and urinary function, with only 12% experiencing local regrowth and a very high overall survival rate of 97%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is watch and wait a safe and effective way to treat rectal cancer in older patients? Haak, HE., Maas, M., Lambregts, DMJ., et al.[2020]

In a study comparing 26 patients using a watch and wait strategy after neoadjuvant treatment to 22 patients who underwent surgery after achieving a pathological complete response, both groups showed similar oncological outcomes, indicating that surgery can be safely deferred for clinical complete responders.

The study found no significant differences in local or distant recurrence rates, disease-free survival (87.9% for watch and wait vs. 80% for surgery), or overall survival (86% for watch and wait vs. 85% for surgery), suggesting that nonoperative management is a viable option for patients with low rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of long-term oncological results of clinical versus pathological responses after neoadjuvant treatment in locally advanced rectal cancer. Coraglio, MF., Eleta, MA., Kujaruk, MR., et al.[2021]

In a study of 793 patients with rectal cancer who achieved a clinical complete response after neoadjuvant chemotherapy and were managed with a watch-and-wait strategy, the probability of remaining free from local regrowth was very high: 97.3% after 3 years and 98.6% after 5 years.

The study suggests that the intensity of surveillance for these patients could be safely reduced if they maintain a clinical complete response for the first 3 years, as the likelihood of remaining free from distant metastasis was also high, at 97.8% after 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study. Fernandez, LM., São Julião, GP., Figueiredo, NL., et al.[2021]

The watch-and-wait approach for rectal cancer patients who achieve a clinical complete response after neoadjuvant chemoradiation shows a 2-year local regrowth rate of 15.7%, with 95.4% of those experiencing regrowth successfully treated with salvage therapies.

There were no significant differences in cancer-specific mortality or overall survival between patients managed with watch-and-wait and those who underwent surgery, suggesting that watch-and-wait could be a safe alternative, although more extensive studies are needed to confirm long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Dossa, F., Chesney, TR., Acuna, SA., et al.[2022]

In a study of 142 rectal cancer patients, 88 showed a clinical complete response (cCR) after treatment with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT), indicating that these treatments can effectively lead to significant tumor reduction before considering a Watch & Wait (W&W) strategy.

The overall regrowth rate was 19%, with a 3-year survival rate of 93%, suggesting that SCRT can lead to sustained cCR and is a viable option for patients in a W&W program, with no significant differences in regrowth rates among the different treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ preservation following short-course radiotherapy for rectal cancer. Nilsson, PJ., Ahlberg, M., Kordnejad, S., et al.[2022]

In a study of 259 rectal cancer patients, those who achieved a clinical complete response and were managed with a watch-and-wait approach had similar 3-year non-regrowth disease-free survival rates compared to those who underwent surgical resection, indicating that the watch-and-wait strategy is oncologically safe.

Patients managed by watch and wait had significantly better colostomy-free survival rates (74%) compared to those who had surgery (47%), suggesting that this approach allows many patients to avoid major surgery and the associated risks of permanent colostomy without compromising their cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Renehan, AG., Malcomson, L., Emsley, R., et al.[2022]

The watch-and-wait approach for patients with locally advanced rectal cancer who achieve a complete clinical response after neoadjuvant treatment offers a noninvasive alternative to radical surgery, potentially improving quality of life and functional outcomes.

This review summarizes key studies supporting the watch-and-wait strategy and provides practical guidance for its implementation, highlighting its role in organ preservation and reducing surgical risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical review of watch-and-wait approach in rectal cancer. Byun, HK., Koom, WS.[2023]

Patients with locally advanced rectal cancer who followed a watch-and-wait strategy after neoadjuvant therapy reported significantly better bowel function compared to those who underwent sphincter-preserving surgery, with a median total score of 76 versus 55 (p < 0.001).

The greatest improvement in bowel function for the watch-and-wait group was observed in the urgency/soilage subscale, indicating that this nonoperative approach may lead to fewer bowel control issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Bowel Function in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy After Neoadjuvant Therapy: A Case-Control Study. Quezada-Diaz, FF., Smith, JJ., Jimenez-Rodriguez, RM., et al.[2022]

Magnetic resonance imaging (MRI) using diffusion-weighted protocols can accurately identify complete responders in locally-advanced rectal cancer patients after neo-adjuvant chemoradiotherapy, which may help in deciding whether to pursue a 'watch and wait' approach instead of surgery.

Positron emission tomography (PET) shows high sensitivity (90.9%) and specificity (80.3%) for predicting complete pathological response, while specific blood biomarkers like the neutrophil to lymphocyte ratio and carcinoembryonic antigen (CEA) levels can further enhance the assessment of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ sparing management in rectal cancer. Are we there yet? Andras, D., Crisan, D., Avram, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adoption of Organ Preservation and Surgeon Variability for Patients with Rectal Cancer Does Not Correlate with Worse Survival. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Is watch and wait a safe and effective way to treat rectal cancer in older patients? [2020]

4. England pubmed.ncbi.nlm.nih.gov

Analysis of long-term oncological results of clinical versus pathological responses after neoadjuvant treatment in locally advanced rectal cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Organ preservation following short-course radiotherapy for rectal cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

A practical review of watch-and-wait approach in rectal cancer. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Patient-Reported Bowel Function in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy After Neoadjuvant Therapy: A Case-Control Study. [2022]

11. Italy pubmed.ncbi.nlm.nih.gov

Organ sparing management in rectal cancer. Are we there yet? [2022]