Non-Operative Management of Patients with Rectal Cancer: Lessons Learnt from the OPRA Trial

Abstract

Over the past decade, the management of locally advanced rectal cancer (LARC) has progressively become more complex. The introduction of total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathological complete response, resulting in excellent long-term oncological outcomes. As a result, non-operative management (NOM) of LARC patients with a clinical complete response (cCR) after neoadjuvant therapy has gained acceptance as a potential treatment option in selected cases. NOM is based on replacement of surgical resection with safe and active surveillance. However, the identification of appropriate candidates for a NOM strategy without compromising oncologic safety is currently challenging due to the lack of an objective standardization. NOM should be part of the treatment plan discussion with LARC patients, considering the increasing rates of cCR, patient preference, quality of life, expectations, and the potential avoidance of surgical morbidity. The recently published OPRA trial showed that organ preservation is achievable in half of rectal cancer patients treated with TNT, and that chemoradiotherapy followed by consolidation chemotherapy may an appropriate strategy to maximize cCR rates. Ongoing trials are investigating optimal algorithms of TNT delivery to further expand the pool of patients who may benefit from NOM of LARC.

Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand?

“…Among the 225 patients offered WW, 81 (36%) developed a regrowth during the follow-up and subsequently underwent salvage TME [37]. Of note, almost 10% of patients undergoing salvage TME had a pCR on final specimen examination [38].…”

Determining the optimal radiation‐surgery interval (RSI) for oncologic proctectomy following radiotherapy for rectal adenocarcinoma

“…Although various forms and courses of radiotherapy have been employed to treat rectal cancer for over 50 years, characterizing the optimal total dose, treatment course, and subsequent timing to oncological proctectomy remains contentious 7,13 . Moreover, recently popularized “total” neoadjuvant chemoradiotherapy (TNT) and nonoperative “watch and wait” (W&W) protocols add more variables to a complex and partially defined equation and often add substantial time to the interval between completing radiotherapy and surgical resection 5,14–17 …”

“…7,13 Moreover, recently popularized "total" neoadjuvant chemoradiotherapy (TNT) and nonoperative "watch and wait" (W&W) protocols add more variables to a complex and partially defined equation and often add substantial time to the interval between completing radiotherapy and surgical resection. 5,[14][15][16][17] Altering the radiation-surgery interval (RSI) offers a series of hypothetical trade-offs for patients requiring proctectomy following radiation. Since the tumoricidal effects of radiation increase over time from exposure, the rates of partial and complete tumor regression improve with longer RSI, which likely impart oncologic benefit.…”

Kommentar zu: Wirksame PD-1-Rezeptorhemmung bei lokal fortgeschrittenem Rektumkarzinom

“…Allerdings kann bei gutem Ansprechen auf eine neoadjuvante Therapie auch ein "watch and wait"-Konzept ohne radikale Chirurgie zum Tragen kommen. In der OPRA-Studie konnte durch eine Induktionsradiochemotherapie gefolgt von einer konsolidierenden Chemotherapie nach 3 Jahren bei immerhin 59 % der Patienten das Rektum erhalten werden [4]. Chirurgie, Radiochemothera-pie, aber auch die intensiveren neoadjuvanten Chemotherapieregime bedingen deutliche und länger persistierende Nebenwirkungen wie z.…”