By: Kiara Sahi, Contributing Writer
Edited by: Elias Azizi, Editor in Chief
A paper published in The New England Journal of Medicine reported that a clinical trial inclusive of 12 patients with locally advanced rectal cancer found every patient in remission without any requirements of chemotherapy or complex surgical procedures (WebMD). Here’s a simple breakdown on the trial that is being called a “cause for great optimism”.
What do we know about rectal cancer?
Rectal cancer is essentially the development of cancer cells in the rectum, which is the region that begins at the last segment of the colon and terminates at the anus. General symptoms include weight loss, fatigue, discolouration in stool, diarrhoea, constipation, and abdominal pain. When it comes to stage 0 and stage 1 rectal cancer, which correspond to the detection of cancer cells on the surface of the rectal lining and the tumour penetrating into the rectal wall and below the lining respectively, patients usually do not experience any indicative symptoms, making routine colonoscopies instrumental in catching the cancer in its early stages. Rectal cancer is seen in both men and women, with men showing a greater likelihood of developing the disease. It is usually diagnosed in patients above the age of 50, but it can also be seen in young adults and adolescents. The treatment of rectal cancer can be tricky in certain cases. While small tumours can be removed surgically through the performance of a transanal endoscopic microsurgery, surgeries involving the partial or complete removal of the rectum and even the anus such as low anterior resection and abdominoperineal resection are required for the removal of large tumours. Chemotherapy, radiotherapy, immunotherapy, and targeted drug therapy are also often utilised in the treatment of rectal cancer. The five-year relative survival rates for localised rectal cancer and regional rectal cancer based on patients diagnosed with rectal cancer between 2011 and 2017 were 90% and 73% respectively. (Cleveland Clinic)
Details on the trial
The trial in its second phase involved 12 patients with locally advanced rectal cancer. The second phase of a clinical trial involves a larger group of patients as compared to its first phase, and its primary objective is to ascertain whether or not the goal of the new treatment is achieved (American Cancer Society). In this particular trial, the patients were administered a monoclonal antibody called dostarlimab, a checkpoint inhibitor, that helps uncover cancer cells so that the body can locate and destroy them. The patients took the required dosage of dostarlimab every three weeks for a period of six months. The initial plan of action was to provide the patients with any required chemotherapy and surgery after they completed the six months of treatment, however, all 12 patients involved in the trial demonstrated a complete clinical response and hence did not require any subsequent treatment. Once the patients completed six months of treatment, they were all subject to regular follow ups for the next six months, after which no tumours were detected via MRI, biopsy, fluorodeoxyglucose positron emission tomography, digital rectal examination, or endoscopic evaluation. (PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer)
Looking ahead, future stages and subsequent development.
While this is “the first time this has happened in the history of cancer” according to Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Centre, we must keep in mind that the development of this particular treatment still has miles to go when it comes to the completion of all phases involved in the trial and the replication of the results. While a significant portion of the medical community welcomes the news of this trial with hopefulness, many doctors are also sceptical about the 100% efficacy of the trial. According to Dr. Alan P. Renook, who specialises in colorectal cancer at the University of California, San Francisco, the absence of any major side effects implied that “either they did not treat enough patients, or, somehow, these cancers are just plain different”. With at least one more phase of trials to look forward to, it is unclear whether this clinical complete response to dostarlimab can actually be understood as a cure for locally advanced rectal cancer. Especially keeping in mind that all 12 patients carried a rare genetic signature on their tumour called mismatch repair deficiency, studies in larger groups will be a necessary step. Since the third phase of a clinical trial generally involves thousands of volunteers grouped into different categories, this phase will provide a greater understanding as to the scope of the treatment and its limitations. (New York Times)
Needless to say, this trial and its incredibly rare result is a beam of hope for the medical community, and we can only hope that these results get replicated in the next few stages to come, not only significantly helping those who suffer from rectal cancer, but providing the medical community with new insight into the treatment of other types of cancer.
Link to cover image: https://static.wixstatic.com/media/178093_297100dcafb341e2b190a659173d32cb~mv2.jpg/v1/fill/w_1000,h_667,al_c,q_90,usm_0.66_1.00_0.01/178093_297100dcafb341e2b190a659173d32cb~mv2.jpg
Sources: https://www.nejm.org/