Abstract
Background
The landscape of locally advanced rectal cancer treatment has shifted over the past decade with the introduction of total neoadjuvant therapy (TNT), enhancing tumor response and oncologic outcomes. Consequently, the concept of organ preservation by means of a watch-and-wait (W&W) strategy has emerged as a viable option for select patients who demonstrate clinical complete responses (cCR) to TNT, thereby limiting the morbidity associated with multimodal treatment. Although there is increasingly robust evidence supporting the notion of organ preservation, the optimal treatment strategy and predictors of treatment response remain outstanding questions. Rectal cancer incidence is expected to rise sharply in developing countries, and the disease is already recognized as a significant public health issue in Chile. Prior to NOAHS-ARC, TNT-based treatment protocols and W&W programs had yet to be implemented in the country.
Methods
This is a single arm, multicenter phase II prospective trial accruing in Santiago, Chile. Patients with histologically proven rectal adenocarcinoma (< 7cm from anal verge) and stage II or III disease will be recruited and consented. Protocol treatment comprises induction short-course radiotherapy (25 Gy in 5 Gy fractions) followed by consolidation chemotherapy (FOLFOX x9 cycles or CAPOX x6 cycles). Patients will undergo response assessment four to eight weeks following completion of chemotherapy. Patients achieving cCR will be offered W&W management while those with incomplete clinical responses (iCR) will undergo total mesorectal exicision (TME). The primary endpoint is rate of complete tumor response, defined as the sum of pathologic complete responses (pCR) and sustained (> 1 year) cCR, which will be compared to the pCR rate of a historical cohort of patients treated with neoadjuvant chemoradiation alone. Accrual of 73 patients is anticipated assuming an estimated combined pCR/sustained cCR rate of 30%. Quality of life measures and functional bowel, urinary, and sexual outcomes will be studied. Additionally, a biorepository of longitudinally archived tissue and plasma samples will be established, in conjunction with serial endoscopic and MRI images.
Discussion
NOAHS-ARC aims to contribute to the ongoing dialogue on organ preservation while also pioneering the first standardized TNT protocol and W&W program in Chile. Additional emphasis on functional outcomes and meticulous data collection for exploratory research endeavors aim to improve patient care both locally and globally.
Trial Registration:
ClinicalTrials.gov identifier: NCT04864067. Registered April 28, 2021.