Could Upfront Chemotherapy Substitute Preoperative Radiochemotherapy?
In patients with locally advanced, resectable rectal adenocarcinoma, preoperative long course chemoradiation or short-course radiation are currently considered the standards of care. Neoadjuvant radiotherapy, along with improvements in surgical techniques and imaging have dramatically reduced the risk of local recurrence. Disappointingly, these advances have not translated into reduction of risk of distant relapse or improvement in overall survival for these patients. Furthermore, pelvic radiation may be associated with several toxicities, both short and long-term. Recent data suggest that not all patients may need neoadjuvant radiotherapy, and that advances in systemic chemotherapy could be leveraged in the neoadjuvant setting to improve risk of both local and distant relapse. Based on these emerging data, several, ongoing, randomized trials are evaluating neoadjuvant approaches limiting the role of radiotherapy. In this chapter, we summarize the current state of knowledge and ongoing trials in this area. We propose that until the results of these trials are available, neoadjuvant chemotherapy without radiation should be considered investigational or only limited to those with clear contraindications to pelvic radiation. We believe these trials will likely show that preoperative chemoradiation may be more appropriate for certain groups of patients, while preoperative chemotherapy may be appropriate for other groups of patients.
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