How Robust is the Evidence for Prehabilitation in Cancer Surgery?: A Systematic Review and Fragility Index Analysis

The number of randomized controlled trials (RCTs) exploring the effectiveness of prehabilitation on improving postoperative outcomes for cancer surgery is increasing. Fragility index (FI) and reverse fragility index (RFI) represent the minimum number of participants whose status needs to change from an "event" to a "non-event," thereby the results change from statistically significant to nonsignificant (or vice versa for RFI). Fragility quotient (FQ) allows for the FI or RFI to be standardized to the sample size of the study. This review aims to examine the robustness of prehabilitation RCTs by assessing their FI, RFI, and FQ.

The Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Medline, and PsycINFO were searched from inception to December 2023. Eligible articles included RCTs, with parallel arm design, evaluating the effectiveness of prehabilitation intervention on the reduction of postoperative complications in selected major oncologic surgeries. FI and RFI were determined using the R fragility package.

After screening 2486 publications, 76 RCTs met inclusion criteria. Most of the included RCTs explored the effectiveness of nutritional prehabilitation (N = 38; 50%). A total of 544 postoperative complication outcomes were reported across all 76 studies, with 25 (4.6%) demonstrating a significant effect and 519 (95.4%) demonstrating a nonsignificant effect of prehabilitation. Overall, the median FI and RFI were 1 (range 1-14) and 4 (range 1-13), respectively.

The current evidence on the effectiveness of prehabilitation for major cancer surgeries is fragile. Changing outcomes for four participants in most studies was sufficient to make a nonsignificant finding significant.