Dr Fakih on the Significance of the PROSPECT Trial in Rectal Cancer

Marwan G. Fakih, MD, Judy & Bernard Briskin distinguished director, Clinical Research, associate director, Clinical Research, codirector, Gastrointestinal Cancer Program, medical director, Judy & Bernard Briskin Center for Clinical Research, City of Hope, expands on long-term findings from the phase 2/3 PROSPECT trial (NCT01515787), and how these findings may influence the optimal use of nonoperative management strategies in locally advanced rectal cancer.

The PROSPECT trial compared the efficacy of neoadjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) and selective chemoradiation with preoperative pelvic chemoradiation and concurrent chemotherapy, which was previously the standard treatment approach for this patient population at the time of the trial's inception, Fakih begins. Since then, the standard has shifted to a total neoadjuvant therapy approach, Fakih notes. Although highly effective, pelvic chemoradiation is associated with several long-term toxicities that can decrease patient quality of life.

Accordingly, the trial aimed to assess whether the selective use of chemoradiation may still provide benefit to patients eligible for sphincter-sparing surgery, Fakih explains. The trial enrolled patients with previously untreated, pathologically confirmed, locally advanced rectal cancer who

were diagnosed with T2 node-positive, T3 node-negative, or T3 node-positive (cT3N+) disease, and were eligible for surgical resection. Notably, the trial targeted a lower-risk patient population by excluding patients with 4 or more lymph nodes with a short axis of more than 1 cm, as well as those with involved circumferential radial margins, Fakih states.

Long-term findings demonstrated that 3 months of neoadjuvant FOLFOX prior to surgery was non-inferior to pelvic chemoradiation in patients who had a response consisting of a tumor reduction of 20% or greater, , Fakih reports. Patients receiving neoadjuvant chemotherapy experienced a lower local recurrence rate of 1.8% vs 1.6% in those receiving chemoradiation therapy. Moreover, the study's primary end point of disease-free survival did not significantly differ between the neoadjuvant chemotherapy and perioperative chemoradiation groups, Fakih details.

Based on these data, patients who are willing to undergo primary surgical resection may not require radiation therapy provided they have non-bulky nodal disease and no threatened circumferential resection margin, Fakih concludes. He emphasizes the importance of offering this potential radiation-sparing strategy when designing individualized treatment plans based on patient preferences and clinical evaluation.