Radiotherapy, a standard part of the protocol in patients with resectable rectal cancer, can be omitted in a substantial proportion of patients without any apparent change in long-term outcome, according to a large phase 3 trial.
“These data show us that we can de-escalate treatment in selected patients and still reach the same high rates of disease-free survival [DFS] over extended follow-up,” reported investigator Deb Schrag, MD, the chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center, in New York City.
Radiation has been a standard in resectable rectal cancer for decades. Over the last 20 years, it has been typically employed before surgery combined with chemotherapy, usually FOLFOX (5-fluorouracil, leucovorin, oxaliplatin). The suspicion that chemotherapy alone might be adequate in at least some patients provided the rationale for an international phase 3 trial called PROSPECT.
In this noninferiority trial, launched in 2012, investigators randomized 1,128 patients with stage T2 node-positive, T3 node-negative or T3 node-positive rectal cancer. In the control group, patients received a standard regimen of FOLFOX plus radiation. In the experimental group, patients received six cycles of FOLFOX alone and then underwent restaging. If the tumor regression exceeded 20%, no radiation was administered before resection. If not, these patients also received chemoradiation.
Presenting the findings at the 2023 annual meeting of the American Society of Clinical Oncology (abstract LBA2), Dr. Schrag reported that at five years, rates of the primary end point of DFS were 78.6% and 80.8% in the control and experimental arms, respectively. Due to greater DFS in the experimental arm, noninferiority was met with a high degree of statistical significance (P=0.005).
At five years, the rates of overall survival (90.2% vs. 89.5%) and freedom from recurrence (98.4% vs. 98.2%), although numerically higher in the experimental arm, did not approach statistical significance.
A pathologic complete response at the time of surgery was achieved in 24% and 22% of those randomized to the experimental and control arms, respectively.
According to Dr. Schrag, patients who forgo radiation will avoid the risk for a sizable list of toxicities that include impaired bowel function, impaired sexual function, infertility, pelvic fracture and increased risk for second malignancies.
Overall, just 9% of patients randomized to the experimental arm of FOLFOX alone ended up receiving neoadjuvant chemoradiation either because tumor shrinkage did not exceed 20% or because they could not tolerate at least five cycles of FOLFOX.
“This is practice-changing,” said invited ASCO expert Pamela L. Kunz, MD, the chief of GI medical oncology at Yale School of Medicine, in New Haven, Conn. “This is really a situation in which less is more. It shows we can avoid major side effects in many patients without compromising efficacy.”
—Ted Bosworth
Dr. Kunz reported no relevant financial disclosures. Dr. Schrag reported financial relationships with Merck.
This article is from the July 2023 print issue.