Their editorial, titled “Minimizing Therapy and Maximizing Outcomes in Rectal Cancer,” is an accompanying communication to a research article titled, “Wait-and-See Policy for Clinical Complete Responders After Chemoradiation for Rectal Cancer,” by Maas et al.
For decades, the accepted protocol has been that surgical therapy is essential for cure of rectal cancer. However, studies have demonstrated that a small percentage of patients can be cured with primary radiation therapy. Rectal cancer therapy seeks to cure the disease without causing substantial long-term side effects.
The research article authors report that preoperative radiation therapy and concurrent chemotherapy for rectal cancer can result in complete disappearance of the tumor and involved nodes without subsequent surgery. Their prospective cohort study evaluated the feasibility and safety of a wait-and-see policy with strict selection criteria and follow-up, concluding that such a policy, using up-to-date imaging techniques and careful follow-up, is feasible and results in promising outcomes at least as good as that of patients with a pathologic complete response after surgery. They propose selection criteria and follow-up that could form the basis for future randomized studies.
Tepper and O’Neil suggest that the current paradigm of waiting only six weeks after radiation therapy to proceed to surgery may underestimate the true benefits of radiation therapy, citing previous studies, including one by Habr-Gama et al, which demonstrated that longer periods between radiation therapy and surgery lead to higher rates of pathologic complete response without the need for surgery.
They explain that the biggest difference between the approach of Maas et al versus that of Habr-Gama is in how complete clinical response was defined. While Habr-Gama relied on CT, clinical exam and endoscopic evaluation, Maas et al used high-quality pelvic MRI along with endoscopic ultrasound, biopsy and clinical evaluation.
Tepper and O’Neil state that “substantially more follow-up and larger numbers of patients will be needed to validate this approach. But this well-conducted study is an excellent start.”
Noting that over the last decade there has been a substantial improvement in chemotherapy for colon and rectal cancers, they state that some clinical trials have shown that radiation therapy plus extended chemotherapy administered before surgery is feasible and raises the possibility that chemotherapy could be used to replace radiation therapy, depending on the precise clinical situation. They present new possible treatment algorithms that could benefit from the increasing power of genomic evaluations that, in the future, might allow for better prediction of which tumors would most likely respond best to radiation therapy and/or chemotherapy and provide improved categorization of low and high risk.
Tepper and O’Neil say, “In contrast to what has been done for decades, the era when all patients with moderately advanced disease received all three treatment modalities - radiation therapy, chemotherapy and surgery, we are entering an era where one of these treatments will likely be eliminated in many patients.” They conclude: “Because all of our treatment modalities have improved, we now have the opportunity to tailor further the primary therapy to one that best suits the individual patient and to truly maximize the benefit to the patient while minimizing the extent of the therapeutic interventions.”