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Background <p>Radical surgery (RS) such as total mesorectal excision (TME) is standard for locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT); however, organ-preserving strategies such as watch-and-wait (W&amp;W) and local excision (LE) aim to reduce surgical morbidity. The comparative efficacy remains unclear.</p> Methods <p>PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to May 15, 2025, without language restrictions, with additional manual screening of reference lists. Studies including patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy and comparing W&amp;W, LE, and/or TME, and reporting relevant oncologic outcomes were included.</p> Results <p>A systematic review and network meta-analysis was conducted on studies published up to April 2025 (PROSPERO, registration number CRD420251024720). A total of 2868 articles were screened, and 32 studies met the inclusion criteria [1-5], comprising data from 4,695 patients for the final network meta-analysis. The risk of bias assessment indicated that most of the included studies had a low risk of bias. Network meta-analysis revealed that compared with TME, both LE and W&amp;W were associated with a lower rate of DM (OR 0.92, 95% CI 0.64-1.32 and OR 0.63, 95% CI 0.40-1.00, respectively). However, the DM rate of the LE group was lower than that of the W&amp;W group, but the difference was not statistically significant (OR 1.17, 95% CI 0.49-2.80). W&amp;W appeared to show a favorable survival trend in OR-based analyses; however, this finding was not confirmed in HR-based analyses, which are more reliable for time-to-event outcomes and were limited in availability.</p> Conclusions <p>In this network meta-analysis, organ-preserving strategies such as W&amp;W and LE demonstrated comparable long-term survival outcomes to TME in selected patients after nCRT. However, these approaches were associated with a substantially increased risk of local recurrence, highlighting an important trade-off between oncologic safety and organ preservation. Therefore, the LE and W&amp;W strategies may be considered as alternative approaches in carefully selected patients with favorable response, provided that strict surveillance and timely salvage interventions are ensured.</p>

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Treatment Strategy Optimization Following Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Network Meta-Analysis

  • 期刊论文

  • 发表日期：

    2026年5月28日

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  • Yutong Wu,
  • Peichen Lv,
  • Yiming Ren,
  • Simiao Tian,
  • Huankun Wang,
  • Lixin Fan

摘要

Background

Radical surgery (RS) such as total mesorectal excision (TME) is standard for locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT); however, organ-preserving strategies such as watch-and-wait (W&W) and local excision (LE) aim to reduce surgical morbidity. The comparative efficacy remains unclear.

Methods

PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to May 15, 2025, without language restrictions, with additional manual screening of reference lists. Studies including patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy and comparing W&W, LE, and/or TME, and reporting relevant oncologic outcomes were included.

Results

A systematic review and network meta-analysis was conducted on studies published up to April 2025 (PROSPERO, registration number CRD420251024720). A total of 2868 articles were screened, and 32 studies met the inclusion criteria [1-5], comprising data from 4,695 patients for the final network meta-analysis. The risk of bias assessment indicated that most of the included studies had a low risk of bias. Network meta-analysis revealed that compared with TME, both LE and W&W were associated with a lower rate of DM (OR 0.92, 95% CI 0.64-1.32 and OR 0.63, 95% CI 0.40-1.00, respectively). However, the DM rate of the LE group was lower than that of the W&W group, but the difference was not statistically significant (OR 1.17, 95% CI 0.49-2.80). W&W appeared to show a favorable survival trend in OR-based analyses; however, this finding was not confirmed in HR-based analyses, which are more reliable for time-to-event outcomes and were limited in availability.

Conclusions

In this network meta-analysis, organ-preserving strategies such as W&W and LE demonstrated comparable long-term survival outcomes to TME in selected patients after nCRT. However, these approaches were associated with a substantially increased risk of local recurrence, highlighting an important trade-off between oncologic safety and organ preservation. Therefore, the LE and W&W strategies may be considered as alternative approaches in carefully selected patients with favorable response, provided that strict surveillance and timely salvage interventions are ensured.