Organ Preservation in Patients with Rectal Cancer Treated with Total Neoadjuvant Therapy

Abstract

BACKGROUND: Retrospective studies suggest that watch-and-wait is a safe alternative to total mesorectal excision in selected patients with a clinical complete response after chemoradiotherapy. OBJECTIVE: This study aimed to determine the proportion of patients with rectal cancer who may benefit from watch-and-wait. DESIGN: This study is a retrospective analysis of data from prospectively maintained databases. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients with stage II or III rectal adenocarcinoma who were treated with total neoadjuvant therapy using induction chemotherapy between 2012 and 2019 under the care of the same surgeon were included. INTERVENTION: Induction-type total neoadjuvant therapy consisted of 8 cycles of leucovorin-fluorouracil-oxaliplatin or 5 cycles of capecitabine-oxaliplatin before chemoradiotherapy. Patients with a clinical complete response were offered watch-and-wait, and patients with residual tumor were offered total mesorectal excision. MAIN OUTCOMES AND MEASURES: Tumor response was assessed with a digital rectal examination, endoscopy, and MRI. Patient characteristics and recurrence-free survival were compared between the watch-and-wait group and the total mesorectal excision group. RESULTS: A total of 88 patients were included in the analysis. One (1%) died during neoadjuvant therapy. Fifty-five patients (62.5%) had an incomplete clinical response and underwent surgery, 10 (18%) of the 55 developed distant metastasis, and 3 (5%) developed local recurrence. The remaining 32 patients (36.3%) had a clinical complete response and underwent watch-and-wait. On average, patients in the watch-and-wait group were older and had smaller, more distal tumors compared with patients in the surgery group. The median radiation dose, number of chemotherapy cycles, rate of adverse events, and length of follow-up did not differ substantively between the total mesorectal excision group and the watch-and-wait group. In the watch-and-wait group, 2 (6%) patients developed tumor regrowth, and one of them had distant metastasis. Recurrence-free survival was significantly higher in the watch-and-wait group. LIMITATIONS: Generalizability, sample size, and follow-up duration were limitations of this study. CONCLUSIONS: Approximately one-third of patients with stage II or III rectal cancer can benefit from a watch-and-wait approach with the aim of preserving the rectum if treated with induction-type total neoadjuvant therapy and followed by an experienced multidisciplinary team. See Video Abstract at http://links.lww.com/DCR/B688. CONSERVACIÓN DE ÓRGANOS EN PACIENTES CON CÁNCER DE RECTO TRATADOS CON TERAPIA NEOADYUVANTE TOTAL ANTECEDENTES: Estudios retrospectivos sugieren que observar y esperar es una alternativa segura a la escisión mesorrectal total en pacientes seleccionados con una respuesta clínica completa después de la quimiorradioterapia. OBJETIVO: Determinar la proporción de pacientes con cáncer de recto que pueden beneficiarse de observar y esperar. DISEÑO: Análisis retrospectivo de datos de bases de datos mantenidas de forma prospectiva. ESCENARIO: Centro Oncológico Integral. PACIENTES: Pacientes consecutivos con adenocarcinoma de recto en estadio II o III tratados con TNT utilizando quimioterapia de inducción entre 2012 y 2019 bajo el cuidado del mismo cirujano. INTERVENCIÓN: La terapia neoadyuvante total de tipo inducción consistió en ocho ciclos de leucovorín-fluorouracilo-oxaliplatino o cinco ciclos de capecitabina-oxaliplatino antes de la quimiorradioterapia. A los pacientes con una respuesta clínica completa se les ofreció observar y esperar, y a los pacientes con tumor residual se les ofreció la escisión mesorrectal total. PRINCIPALES RESULTADOS Y MEDIDAS: La respuesta del tumor se evaluó con un tacto rectal, endoscopia y resonancia magnética. Se compararon las características de los pacientes y la supervivencia libre de recurrencia entre el grupo de observación y espera y el grupo de escisión mesorrectal total. RESULTADOS: Se incluyó en el análisis a un total de 88 pacientes. Uno (1%) murió durante la terapia neoadyuvante. Cincuenta y cinco pacientes (62.5%) tuvieron una respuesta clínica incompleta y se sometieron a cirugía; 10 (18%) de los 55 desarrollaron metástasis a distancia y 3 (5%) desarrollaron recidiva local. Los 32 pacientes restantes (36.3%) tuvieron una cCR (respuesta clínica completa) y se sometieron a observar y esperar. En promedio, los pacientes del grupo de observación y espera eran mayores y tenían tumores más pequeños y distales en comparación con el grupo de cirugía. La dosis mediana de radiación, el número de ciclos de quimioterapia, la tasa de eventos adversos y la duración del seguimiento no difirieron sustancialmente entre el grupo de escisión mesorrectal total y el grupo de observación y espera. En el grupo de observación y espera, 2 (6%) pacientes desarrollaron recrecimiento del tumor y uno de ellos tuvo metástasis a distancia. La supervivencia libre de recurrencia fue significativamente mayor en el grupo de observación y espera. LIMITACIONES: Generalizabilidad, tamaño de la muestra, duración del seguimiento. CONCLUSIONES: Aproximadamente un tercio de los pacientes con cáncer de recto en estadio II o III pueden beneficiarse de un abordaje de observación y espera con el objetivo de preservar el recto si se tratan con terapia neoadyuvante total de tipo inducción y son seguidos por un equipo multidisciplinario experimentado. Consulte Video Resumen en http://links.lww.com/DCR/B688.

Development of a method for digital assessment of tumor regression grade in patients with rectal cancer following neoadjuvant therapy

“… 22 Studies have used deep learning to examine prognosis, identify prognostic biomarkers, and in predicting molecular profiles, based on standard H&E-stained slides in CRC. 23 , 24 , 25 , 26 As new treatment strategies with total neoadjuvant treatment and immunotherapy emerge, 27 , 28 , 29 an accurate tumor regression grade is highly important as the pathological response often is used as endpoint in clinical trials.…”

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

“…This pattern was also observed in data reported from the IWWD [54]; in patients with local regrowth, the incidence of distant metastasis was 18%, while in those without it was 5%. Jimenez-Rodriguez et al also found a high rate of distant metastases (~50%) in the small number of patients (6%) treated with TNT by a single surgeon that actively performed WW [59] who experienced local regrowth.…”

Surgical Treatment of Low-Lying Rectal Cancer: Updates

“…Jimenez-Rodrigues et al [ 164 ] analyzed 88 patients with stage II and III rectal cancer who received an induction-type total neoadjuvant therapy (TNT) consisting of 8 cycles of FOLFOX or XELOX before chemoradiotherapy between 2012 and 2019. They reported that TNT using induction chemotherapy followed by chemoradiotherapy could achieve a cCR in 36.2% of patients, and watch-and-wait protocol could be advised.…”

“…As colorectal surgeons, we have experienced patients who show a cCR after NCRT. Furthermore, the adoption of induction or consolidation chemotherapy in total neoadjuvant treatments [ 164 ] has increased the incidence of cCR. The watch-and-wait strategy also got more attention because salvage surgery for regrowing tumors during follow-up did not compromise an oncologic outcome.…”