Q&A on Evolving Rectal Cancer Management

Renowned colorectal surgeon and outcomes researcher Marylise Boutros, MD, recently joined Cleveland Clinic in Florida as Director of Research for the Digestive Disease Institute, where she now leads outcomes-driven research and initiatives for the region.

Dr. Boutros specializes in advanced, minimally invasive approaches to benign and malignant colorectal and anorectal diseases. Previously, she served as head of the Colon and Rectal Surgery Research Program at Jewish General Hospital, a McGill University teaching hospital in Montreal, Canada.

As a researcher, Dr. Boutros is focused on the functional outcomes of rectal cancer treatment including low anterior resection syndrome (LARS). She is encouraged by the evolving approaches to disease management that are improving overall survival while addressing the impact on quality of life.

Consult QD recently talked with Dr. Boutros about some of the changes underway in rectal cancer management, and here are highlights from that conversation.

How has overall survival changed in recent years for patients with rectal cancer?

Rectal cancer survival rates have been climbing in recent years. The American Cancer Society reports that the 5-year overall survival rate is 68%, but for localized disease it has reached 90%.

My colleagues here at Cleveland Clinic Weston Hospital in Florida conducted a retrospective, observational study last year that revealed the gains we’ve made. They looked at data from the National Cancer Database (NCDB) that included 318,548 patients diagnosed with rectal adenocarcinoma from 2004 through 2019.

After dividing them into four equal periods, the researchers determined that the median (IQR) overall survival significantly increased from 83.1 months in period 1 (2004-2007) to 92.1 months in period 3 (2012-2015). The last period (2016-2019) wasn’t included in the survival analysis due to insufficient length of follow-up.

The improvement is even more noteworthy when you consider the concurrent increase in more locally advanced (stage III) and metastatic (stage IV) disease being diagnosed. According to the study, 42% of patients in period 1 had stage III or IV rectal cancer versus 49.5% in period 3. This tells me that despite more advanced disease presentation, our treatment gains are headed in the right direction.

While the study doesn’t draw a direct line from any one treatment advancement to overall patient survival, it demonstrates that physicians caring for these patients are making better use of neoadjuvant therapies, performing better surgeries, and engaging in better decision making.

How is the use of neoadjuvant therapies changing?

In this particular study, the team observed a significant increase in the use of chemotherapy (36.8% vs 47.0%) and immunotherapy (0.4% vs 6.5%), when comparing period 1 to period 4. This 16 fold increase in immunotherapy use is especially important for patients with tumors that show high microsatellite instability due to mutations in DNA mismatch repair genes as they respond poorly to chemotherapy.

There was also an increase in the use of neoadjuvant radiotherapy across the periods studied (28.6% in period 1 to 34.3% in period 4) but a decline in adjuvant radiotherapy (12.9% to 6.0%). When surgery follows radiotherapy, the radiated bowel is likely to be removed. This is preferable to radiating the newly constructed bowel in the case of adjuvant radiotherapy and results in better functional outcomes for patients.

As we learned from the phase III PROSPECT trial presented at this year’s annual meeting of the American Society of Clinical Oncology, preoperative therapies are continuing to evolve. This study demonstrated that certain patients with locally advanced rectal cancer can be treated with neoadjuvant chemotherapy in place of preoperative chemoradiotherapy while achieving equivalent oncologic results. With more options, patients have the ability to weigh treatment toxicities and determine what’s best for them.

What surgical trends are contributing to improved outcomes?

In the surgical space we are seeing a continued expansion of minimally invasive approaches. This was reflected in the database analysis which saw a 50% reduction in open surgery from period 2 to period 4 (60.1% vs 30.1%). While more patients are undergoing laparoscopic surgery than open or robotic surgery (41.4% vs 30.1% vs 28.4 in period 4), the rapid adoption of robotic surgery in the past decade is particularly notable. In addition, there is an increased use of sphincter-saving lower anterior resection and a decrease in abdominoperineal resection (OR 0.82; 95%CI 0.79-0.85).

With better surgery, we have also observed a reduced conversion rate among patients who underwent laparoscopic or robotic resections. It decreased from 11.2% in period 2 to 7.3% in period 4. Due to the better recovery afforded by minimally invasive surgery as well as better post-operative care pathways, patients are experiencing a better recovery as demonstrated by a 2-day shorter hospital stay, according to the analysis.

Another surgical quality indicator is the number of harvested lymph nodes, which increased from a median (IQR) of 11 in the first period to 15 in the last period. Current guidelines recommend a minimum of 12 harvested lymph nodes as the standard of care to ensure accurate staging.

Overall, there is a general shift to less surgery (30.9% in period 1 vs 40.8% in period 4). This is not unexpected in light of the increased use of neoadjuvant therapies where a complete response can allow for a non-operative management approach with watchful waiting.

What findings suggest better decision making is involved?

In the database analysis, my colleagues found that the median (IQR) time from diagnosis to first treatment increased by 11 days, without exceeding the 60-day window recommended by the National Accreditation Program for Rectal Cancer. This delay is actually a positive as it demonstrates the extra care involved in acquiring the required pretreatment imaging studies and the multidisciplinary tumor board discussions that have been shown to improve patient outcomes.

Rectal cancer management requires an expert team approach that includes specialists in medical and radiation oncology, colorectal surgery, pathology and radiology. In the form of a tumor board, they work together to develop a multimodal treatment plan that is uniquely tailored to each patient and that reflects the patient’s goals and values. Again, the observed trend of increased survival despite more advanced disease presentation tells me that there is an increasing use of multidisciplinary team decision making and neoadjuvant treatment strategies. We are certainly heading in the right direction.