ABSTRACT
Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.
ABSTRACT
Therapeutic goal for locally advance rectal cancer (LARC) patients includes long-term survival and function preservation of pelvic organs. During the recent two decades, treatment strategy for LARC is gradually shifing to minimally invasive surgery, even avoiding a major surgery. "Watch and wait (W&W)" strategy is effective in dramatically decreasing surgical trauma and significantly improving preservation of defecation, urination and sexual function. Total neoadjuvant therapy (TNT) shifts all or part of adjuvant chemotherapy to the neoadjuvant phase and has showed obvious advantage in tumor shrinkage and complete clinical response (cCR) achievement. This article will summarize the transition of treatment strategy of LARC towards W&W from standard treatment. After more than ten years of development, both NCCN and ESMO guidelines recommend stratified neoadjuvant treatment considerations based on distinct risk classifications and especially suggest TNT for LARC patients with advanced diseases, which affirms the value of TNT in tumor shrinkage. Although accumulating data show that pelvic control and organ preservation using W&W strategy after cCR is equal or non-inferior to standard surgery, impact on long-term survival still needs prospective randomized controlled study; no consensus has been achieved for the detail of the W&W strategy. Thus W&W strategy is suggested to applied in hospitals specialized in the treatment of rectal cancer within the framework of multiple disciplinary treatment. In view of special medical conditions of our country, we still need to accumulate more experience and data of W&W strategy for rectal cancer patients with appeals for sphincter preservation and actively participate in international researches.
ABSTRACT
In recent years,neoadjuvant treatment followed by esophagectomy has been the standard treatment strategy for locally advanced esophageal cancer.Pathological response,especially complete pathological response (pCR),indicates better overall survival.With respect to complete clinical response (cCR) after neoadjuvant treatment,some researchers propose that definitive chemoradiotherapy could be an alternative to esophageetomy.The authors analyze and summarize correlation between cCR and pCR,and survival benefits of watch and wait after cCR.The authors think cCR alone could not be the precondition for the debate,unless combined with an effective predition of pCR based on clinical and molecular biomarkers.In this way,a prudent selection of patients followed by optimal therapy could be an important direction of individual management for locally advanced esophageal cancer.
ABSTRACT
Objetivos: Describir características clínicas, histopatológicas y desenlaces de pacientes con cáncer localmente avanzado de recto y respuesta clínica completa posterior a la neoadyuvancia, sin manejo quirúrgico. Métodos: Estudio de cohorte retrospectiva de pacientes con cáncer de recto estadios II y III, llevados a quimiorradiación, en seguimiento clínico. Se evaluó supervivencia libre de enfermedad, global y tasa de recaída. Se describen características biológicas (Kras, Ki67, p53) y morfológicas del tumor (grado, invasión linfovascular y perineural). Resultados: Entre enero de 2003 y junio de 2013, 19 pacientes con cáncer localmente avanzado de recto y respuesta clínica completa postneoadyuvancia, no aceptaron el tratamiento quirúrgico radical. Con mediana de seguimiento de 21 meses (4-92 meses), se presentaron recaídas del: 21% en el primer año, 36% a los 3 años y 42% a los 5 años (total: 8 pacientes). Se presentó recaída local en 50% de casos, regional en 50% y no hubo recaída sistémica. La tasa estimada de recaída local fue 2,3 recaídas por 100 pacientes/mes (IC 95%:1,21-4,5) y de recaída regional 1,3 recaídas por 100 pacientes/mes (IC 95%:0,5-3,1). No se estableció relación, entre la expresión de factores biológicos del tumor primario y los desenlaces. Conclusiones: Se ratifica la indicación del tratamiento quirúrgico radical, posterior a la neoadyuvancia, en todos los pacientes con cáncer localmente avanzado de recto. Las bajas tasas de recaída local y regional de nuestra serie, sugieren la posibilidad de resección local u observación, en casos seleccionados. La individualización y deseo del paciente, debe orientar la toma de decisiones.
Objectives: To describe the clinical and histopathological characteristics and outcomes of patient with non-surgically managed locally advanced rectal cancer and a complete clinical response to neoadjuvant treatment. Methods: A retrospective study was conducted on a cohort of patients with stages II and III rectal cancer, on clinical follow up after subjected to chemoradiotherapy. The overall disease free survival and recurrence rates were evaluated. The biological (Kras, Ki67, p53) and morphological (grade, lymphovascular and perineural invasion) characteristics of the tumor were recorded. Results: Between January 2003 and June 2013, a total of 19 patients with locally advanced rectal cancer and a complete clinical response after neoadjuvant treatment, did not accept radical surgical treatment. With a median follow-up of 21 months (range 4-92 months), the recurrences were: 21% in the first year, 36% at 3 years, and 42% at 5 years (total: 8 patients). There was local recurrence in 50% of the cases, regional in 50%, and there were no systemic recurrences. The estimated local recurrence rate was 2.3 recurrences per 100 patients/month (95% CI; 1.21 - 4.5), and a regional recurrence of 1.3 recurrences per 100 patients/month (95% CI: 0.5 - 3.1). No relationship was found between the expression of biological factors of the primary tumor and the outcomes. Conclusions: The indication for radical surgical treatment after neoadjuvant treatment is demonstrated in all patients with locally advanced rectal cancer. The low local and regional recurrence rates of this series suggest the possibility of local resection or observation in selected cases. Individualization and the wishes of the patient must be taken into account when making decisions.