Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials.

A few months ago, results from two randomised phase III trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were presented (RAPIDO and PRODIGE 23), consistently showing better short- and long-term outcomes with TNT as compared with standard neoadjuvant long-course chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). These results represent corroborating evidence in support of a practice that many centres had already implemented based on promising preliminary data. Also, they provide new, high-level evidence to endorse TNT as a new management option in the treatment algorithm of stage II-III rectal cancer in those centres where CRT and SCRT have long remained the only accepted standard neoadjuvant treatments. Having two consistently positive trials is certainly reassuring regarding the potential of TNT as a general treatment approach. Nevertheless, substantial differences between these trials pose important challenges in relation to the generalisability and applicability of their results, and translation of the same into practical clinical recommendations. In this article, we address a number of key questions that the RAPIDO and PRODIGE 23 trials have raised among the broad community of gastrointestinal oncologists, proposing an interpretation of the data that may help the decision making, and highlighting grey areas that warrant further investigation.

Adjuvant chemotherapy for rectal cancer: Current evidence and recommendations for clinical practice.

While adjuvant chemotherapy is an established treatment for pathological stage II and especially stage III colon cancer, its role in the multimodal management of rectal cancer remains controversial. As a result, there is substantial variation in the use of this treatment in clinical practice. Even among centres and physicians who consider adjuvant chemotherapy as a standard treatment, notable heterogeneity exists with regard to patient selection criteria and chemotherapy regimens. The controversy around this topic is confirmed by the lack of full consensus among national and international clinical guidelines. While most of the clinical trials do not support the contention that adjuvant chemotherapy may improve survival outcomes if pre-operative (chemo)radiotherapy is also given, these suffer from many limitations that preclude drawing definitive conclusions. Nevertheless, in the era of evidence-based medicine, physicians should be guided by the available data and refrain from extrapolating results of adjuvant colon cancer trials to inform treatment decisions for rectal cancer. Patients should be informed of the evidence gap, be given the opportunity to carefully discuss pros and cons of all the possible management options and be empowered in the decision making. In this article we review the available evidence on adjuvant chemotherapy for rectal cancer and propose a risk-adapted decisional algorithm that largely relies on informed patient preferences.