Flom Emily, Schultz Kurt S, Pantel Haddon J, Leeds Ira L
Division of Colon and Rectal Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520, USA.
Cancers (Basel). 2023 Dec 15;15(24):5853. doi: 10.3390/cancers15245853.
The modern rectal cancer treatment paradigm offers additional opportunities for organ preservation, most notably via total neoadjuvant therapy (TNT) and consideration for a watch-and-wait (WW) surveillance-only approach. A major barrier to widespread implementation of a WW approach to rectal cancer is the potential discordance between a clinical complete response (cCR) and a pathologic complete response (pCR). In the pre-TNT era, the identification of predictors of pCR after neoadjuvant therapy had been previously studied. However, the last meta-analysis to assess the summative evidence on this important treatment decision point predates the acceptance and dissemination of TNT strategies. The purpose of this systematic review was to assess preoperative predictors of pCR after TNT to guide the ideal selection criteria for WW in the current era. An exhaustive literature review was performed and the electronic databases Embase, Ovid, MEDLINE, PubMed, and Cochrane were comprehensively searched up to 27 June 2023. Search terms and their combinations included "rectal neoplasms", "total neoadjuvant therapy", and "pathologic complete response". Only studies in English were included. Randomized clinical trials or prospective/retrospective cohort studies of patients with clinical stage 2 or 3 rectal adenocarcinoma who underwent at least 8 weeks of neoadjuvant chemotherapy in addition to chemoradiotherapy with pCR as a measured study outcome were included. In this systematic review, nine studies were reviewed for characteristics positively or negatively associated with pCR or tumor response after TNT. The results were qualitatively grouped into four categories: (1) biochemical factors; (2) clinical factors; (3) patient demographics; and (4) treatment sequence for TNT. The heterogeneity of studies precluded meta-analysis. The level of evidence was low to very low. There is minimal data to support any clinicopathologic factors that either have a negative or positive relationship to pCR and tumor response after TNT. Additional data from long-term trials using TNT is critical to better inform those considering WW approaches following a cCR.
现代直肠癌治疗模式为器官保留提供了更多机会，最显著的是通过全新辅助治疗（TNT）以及考虑采用仅观察等待（WW）的监测方法。直肠癌广泛采用WW方法的一个主要障碍是临床完全缓解（cCR）与病理完全缓解（pCR）之间可能存在不一致。在TNT时代之前，已经对新辅助治疗后pCR的预测因素进行了研究。然而，上一次评估这一重要治疗决策点的汇总证据的荟萃分析早于TNT策略的接受和传播。本系统评价的目的是评估TNT后pCR的术前预测因素，以指导当前时代WW的理想选择标准。进行了详尽的文献综述，并全面检索了截至2023年6月27日的电子数据库Embase、Ovid、MEDLINE、PubMed和Cochrane。检索词及其组合包括“直肠肿瘤”、“全新辅助治疗”和“病理完全缓解”。仅纳入英文研究。纳入了临床2期或3期直肠腺癌患者的随机临床试验或前瞻性/回顾性队列研究，这些患者除了接受以pCR为测量研究结果的放化疗外，还接受了至少8周的新辅助化疗。在本系统评价中，对9项研究进行了审查，以确定与TNT后pCR或肿瘤反应呈正相关或负相关的特征。结果定性地分为四类：（1）生化因素；（2）临床因素；（3）患者人口统计学特征；（4）TNT的治疗顺序。研究的异质性排除了荟萃分析。证据水平为低至极低。几乎没有数据支持与TNT后pCR和肿瘤反应呈负相关或正相关的任何临床病理因素。来自使用TNT的长期试验的更多数据对于更好地为那些考虑在cCR后采用WW方法的人提供信息至关重要。
