As a physician, one of the most challenging types of cancer to treat is locally advanced rectal cancer. These tumors have often grown to the point where surgery alone is not enough to remove all of the cancer and prevent recurrence. That’s why the standard of care for these patients is a treatment approach called “total neoadjuvant therapy.”
Total neoadjuvant therapy involves using radiation and chemotherapy upfront, before complete surgical resection. The idea is to shrink the tumor as much as possible, making it easier to remove during surgery and increasing the chances of a successful outcome in terms of reducing local and distal recurrent disease. This approach has been shown to be effective in many patients with locally advanced rectal cancer.
However, not all rectal cancers are the same. A subset of rectal cancers can demonstrate deficiency in the mismatch repair proteins. These tumors tend to be more aggressive and are less responsive to standard treatments however are very sensitive to immunotherapy using checkpoint inhibitors.
That’s why a recent study published in June 2022 NEJM was so exciting The study looked at the use of a new treatment called dostarlimab, an anti-PD-1 monoclonal antibody, in patients with locally advanced rectal cancer that is deficient in mismatch repair. The results were remarkable: all 12 patients in the study had a clinical complete response after using immunotherapy alone, meaning there was no evidence of tumor on imaging or physical examination. Although the protocol required planned chemoradiation and/or surgery if there was residual malignant disease, none of the 12 patients went on to receive chemoradiation or surgery after 6 months of immunotherapy!
This is a small study, and more research is needed to confirm these findings and to understand the long-term outcomes for patients. But the results are highly encouraging and suggest that checkpoint inhibitors may be a new treatment option for a subset of patients with locally advanced rectal cancer that is difficult to treat and sparing the need “TNT or total neoadjuvant therapy”.
It’s important to note that this study only includes the subset of rectal cancer patients that have evidence of mismatch repair deficiency, and it’s not recommended for most rectal cancer patients that are MSS. This is an important point as dostarlimab is an immunotherapy that targets a specific type of cancer cells with MSI or MMR-Deficient tumor types. Locally advanced rectal cancer is a challenging disease to treat, and total neoadjuvant therapy is the standard of care for most. But for a subset of patients with mismatch repair-deficient rectal cancer, this new study provides tremendous hope that immunotherapy may be an effective new treatment option.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
Embrace the opportunity to engage with Dr. Sajeve’s expertise, and feel empowered to explore the vast expanse of oncology with renewed curiosity and understanding on “Ask MedOnCMD“