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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a treatment for individuals with low rectal cancer who have responded well to chemoradiotherapy (a combination of chemotherapy and radiation). Instead of surgery, the trial examines non-operative management, also known as "Watch and Wait" or "Surveillance with Selective Delayed Surgery." This approach involves closely monitoring patients to detect any cancer recurrence. The trial aims to determine if this method is as effective and safe as surgery by assessing cancer recurrence rates and the success of any necessary delayed surgery in removing all visible cancer. Suitable candidates have completed their initial treatment and show no signs of cancer, according to medical evaluations, approximately 8 to 10 weeks afterward. As an unphased trial, this study provides patients the chance to explore innovative management strategies that could improve their quality of life without immediate surgery.

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 prior data suggests that non-operative management is safe for patients with low rectal cancer?

Research has shown that for some patients with rectal cancer, a non-surgical approach can be safe if they respond well to initial treatments like chemotherapy and radiation. Studies, including those from the International Watch and Wait database, have demonstrated good results. This method allows patients to avoid surgery and instead be closely monitored for any signs of cancer recurrence.

Reports indicate that patients choosing this non-surgical path generally experience a good quality of life and maintain normal functions. The National Comprehensive Cancer Network (NCCN) supports this "watch-and-wait" strategy. However, regular check-ups are essential. Patients in these studies undergo frequent monitoring through physical exams, scopes, and scans to detect any cancer regrowth early.

While there is a risk of local cancer recurrence, the regular follow-up program is designed to manage this effectively. Overall, this non-surgical option is considered safe and viable for some patients, offering a way to avoid the complications associated with surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard surgical treatments for rectal cancer, non-operative management offers a different approach by focusing on active monitoring rather than immediate surgery. This method is unique because it targets patients who show a complete clinical response after chemoradiotherapy, meaning their tumor appears to have shrunk or disappeared. Researchers are excited about this approach as it could potentially spare patients from invasive surgery and its associated risks, while still effectively managing the cancer through vigilant follow-up with regular clinical visits, endoscopy, and imaging. This could improve the quality of life for patients by reducing recovery time and preserving normal rectal function.

What evidence suggests that non-operative management is effective for low rectal cancer?

Research shows that for some rectal cancer patients, avoiding surgery can be effective, especially after chemotherapy and radiation. In this trial, participants will undergo non-operative management, known as the "watch-and-wait" approach, which involves closely monitoring the patient instead of performing surgery. Studies have found that this method can maintain quality of life without increasing the risk of cancer recurrence. Evidence suggests that many patients who choose this non-surgical method avoid major surgery and still achieve good health outcomes. The International Watch and Wait Database reported positive long-term results, with many patients not experiencing tumor regrowth. These findings suggest that this approach can be a safe and effective alternative to surgery for managing rectal cancer in certain cases. ^{1 3 6 7 8}

Who Is on the Research Team?

Erin Kennedy

Principal Investigator

Sinai Health System

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11230012/

Non-operative management of rectal cancer In this editorial, we highlight the main controversies on NOM of rectal cancer, with implications for future research directions.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827328

Challenges of Surveillance in Implementing Nonoperative ... These findings suggest that adherence to recommended surveillance guidelines was not achieved for most patients with rectal cancer undergoing nonoperative ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1477510/full

Nonoperative management of rectal cancer Data from the International Watch and Wait ... Long-term quality of life and functional outcome of patients with rectal cancer following a watch-and-wait approach ...

4. cureus.com cureus.com/articles/373581-non-operative-management-of-locally-advanced-rectal-adenocarcinoma-using-a-watch-and-wait-approach-a-report-of-two-cases

Non-operative Management of Locally Advanced Rectal ... We present two cases of rectal adenocarcinoma in which patients underwent total neoadjuvant therapy, achieved a complete clinical response, and ...

5. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(22)00544-1/fulltext

Watch-and-Wait is an Option in Rectal Cancer Patients The organ-preservation approach for rectal cancer has been explored, in an attempt to improve a patient's quality of life by prevention of TME surgery.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11659252/

Nonoperative management of rectal cancer - PMC Data from the International Watch and Wait ... Long-term quality of life and functional outcome of patients with rectal cancer following a watch-and-wait approach ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01369

From Clinical Trials to Practice: Anticipating and ... The promising oncologic outcomes associated with the nonoperative management of rectal cancer led to the NCCN endorsement of watch-and-wait ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000425

Total neoadjuvant treatment, non-operative management ... Custers, et al. Long-term quality of life and functional outcome of patients with rectal cancer following a watch-and-wait approach. JAMA Surg, 158 (5) (2023) ...