Pilot Study Shows Promise of Neoadjuvant Chemotherapy Without Routine Radiotherapy in Patients With Locally Advanced Rectal Cancer


Key Points

  • A strategy of neoadjuvant chemotherapy without routine chemoradiation did not appear to adversely affect outcomes.
  • All patients had R0 resection, with two who did not complete neoadjuvant chemotherapy due to toxicity having preoperative chemoradiation.

Neoadjuvant chemoradiotherapy delays administration of optimal chemotherapy in stage II to III rectal cancer. In a pilot study reported in the Journal of Clinical Oncology, Schrag et al assessed outcomes with neoadjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin)/bevacizumab (Avastin) with selective use of chemoradiotherapy. They found that this strategy, which is now being assessed in a phase III trial, does not appear to compromise outcome.

Study Details

This phase II study included 32 patients with clinical stage II to III rectal cancer at Memorial Sloan-Kettering Cancer Center who were candidates for low anterior resection with total mesorectal excision. Patients received six cycles of FOLFOX plus bevacizumab in cycles 1 to 4. Those with stable or progressive disease were to have radiation before total mesorectal excision; responders were to have immediate excision. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX for six cycles was recommended, but regimens were left to the discretion of the clinician. The primary outcome was R0 resection rate.


Two patients did not complete preoperative chemotherapy due to cardiovascular toxicity, with both having preoperative chemoradiotherapy followed by R0 resection. All 30 patients who completed preoperative chemotherapy had tumor regression and R0 resection without preoperative radiotherapy. Thus, the R0 resection rate was 100%, and the rate of completion of neoadjuvant chemotherapy was 94%. One patient had postoperative radiation therapy.

The pathologic complete response rate to chemotherapy was 25% (8 of 32 patients), the 4-year local recurrence rate was 0%, 4-year disease-free survival was 84%, and 4-year overall survival was 91%. Four patients (12.5%) developed metastatic disease, involving the lung in each. Three patients died, two due to metastatic rectal cancer and one due to postoperative complications.

The investigators concluded, “For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.”

Leonard B. Saltz, MD, of Memorial Sloan-Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The study was funded by Genentech. For full disclosures of the study authors, visit

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