Treatment strategy for locally advanced rectal cancer

The treatment of patients with rectal cancer is undergoing momentous transformation. Surgical removal of the rectum and the mesorectal envelope was the mainstay of the treatment for many years. Radiation therapy was first added to reduce the risk of local recurrence in patients with advanced disease. Extrapolating from colon cancer, systemic chemotherapy was also added to reduce the risk of distant metastasis, the main threat to patient’s life. While this trimodality therapy has proven effective in controlling the disease, it is associated with significant morbidity and functional sequela that impair patient’s quality of life permanently. learned While new sequences and combinations of these sequences and even some additional treatment intensification are aimed to increase tumor response and patient survival, the fact is that in the absence of more effective chemotherapy agents the added benefit in terms of patient survival are marginal and often results in increased toxicity. New trends in the treatment of rectal cancer should aim to reduce morbidity and preserve quality of life without compromising cure. This can be achieved through selective treatment de-intensification.
One of the lessons learned in recent years is that rectal cancer is more responsive to chemotherapy and radiation that previously thought. At least 50% of early stage rectal cancer respond to chemoradiation and more than 50% of locally advanced rectal cancer can be eradicated with a combination of chemoradiation and systemic chemotherapy. In addition, there is ample evidence that some rectal cancers also respond to systemic chemotherapy alone. Therefore the future treatment of rectal cancer patients should be based on the selective use of these treatment modalities with the goal of achieving objectives previously set based on tumor’s characteristics (size, stage, location) and patient’s age, gender, performance and expectations. In this model some patients may be treated with surgery alone, others may benefit from tumor shrinkage with systemic chemotherapy with the goal of avoiding radiation, and others may require chemoradiation followed by consolidation systemic chemotherapy with the goal of achieving maximal tumor response and achieving organ preservation.
The advances in understanding the molecular biology of colorectal cancer has not translated so far into biomarkers of response or effective medical therapies. New biomarkers and therapies are now emerging - immunotherapy for MSI tumors - that hopefully will result in new treatment paradigms for rectal cancer patients.