Rectal cancer treatment: an embarrassment of riches?

Until recently, the issue of the optimal choice of neo-adjuvant therapy for rectal cancer appeared to have been resolved. Early-stage rectal cancer proceeded directly to surgical resection, while locally advanced tumours required either short-course radiation therapy or long-course chemoradiotherapy (LCCRT).1 How quickly the landscape has changed!

With the publication of the PROSPECT Trial (Preoperative Treatment of Locally Advanced Rectal Cancer) this month, yet another treatment option has been added to the armamentarium. This was a multi-centre, prospective, randomized non-inferiority trial of neoadjuvant FOLFOX versus chemoradiotherapy (CRT) for intermediate-risk rectal cancer. The primary endpoint was disease-free survival; secondary endpoints included overall survival, R0 resection, pathologic complete response (pCR) and toxicity. The study included 1128 patients (FOLFOX n = 585; CRT n = 543) with intermediate risk (T2N+, T3N0, T3N+, candidates for sphincter-sparing surgery). In this patient group, FOLFOX alone was not inferior in terms of disease-free survival. Further, this group reported lower rates of fatigue and neuropathy, and better sexual function at 12 months after surgery.2 The authors acknowledge the possibility of over-treatment as adjuvant chemotherapy was recommended in both patient groups, irrespective of pathological outcomes.