ASO Author Reflections - Walking on Thin Statistical Ice - Why Prehabilitation Evidence in Cancer Surgery May Be More Fragile Than We Think

Sep 29, 2026

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ASO Author Reflections discusses prehabilitation in cancer surgery and argues that the supporting randomized trial evidence may be more statistically fragile than commonly assumed. A systematic review of 76 prehabilitation RCTs reported many non-significant findings, with results sensitive to changes in a very small number of patients. High risk of bias in most studies further weakens reliability. The reflection calls for more rigorous methods, larger samples, broader outcome assessment beyond statistical significance, and fragility analyses in ERAS trials.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

PAST

Clinical context and rationale for prehabilitation evidence

PRESENT

Fragility index, results sensitivity, and risk of bias findings

FUTURE

Recommendations for future research and broader fragility analysis

Ann Surg Oncol (2026) 33:1089–1090 [https://doi.org/10.1245/s10434-025-18517-w](https://doi.org/10.1245/s10434-025-18517-w) ASO AUTHOR REFLECTIONS ASO Author Reflections: Walking on Thin Statistical Ice: Why Prehabilitation Evidence in Cancer Surgery May Be More Fragile Than We Think Sarah Cook, MD1,2, Bora Kim, PhD3, Xiaoqiu Liu, PhD4, Mark Hancock, PhD5, Michael Solomon, DMed1,2,6, Cherry Koh, PhD1,2,6, Sascha Karunaratne, PhD1,2, Kate Alexander, BMedSci1,2, and Daniel Steffens, PhD1,2,5,7 1Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, Australia; 3The Daffodil Centre, The University of Sydney, and Cancer Council NSW, Sydney, Australia; 4Statistics Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; 5Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia; 6Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, Australia; 7Career Development Fellow, Cancer Institute New South Wales, Sydney, Australia PAST Surgical oncology plays a central role in cancer care, with an estimated 12 million people globally requiring surgical treatment for cancer in 2015 alone. 1 Despite its survival benefits, postoperative morbidity remains high, and studies have found that reducing postoperative complications can lead to improved long-term survival outcomes.2 This recognition has led to growing interest in prehabilitation, interventions designed to enhance postsurgical recovery by mitigating surgical stress through nutritional, functional, and psychological interventions.3,4 Although emerging evidence from randomized controlled trials (RCTs) appears promising, the robustness of this evidence has come under scrutiny, prompting the use of metrics such as the fragility index (FI), the reverse fragility index (RFI), and the fragility quotient (FQ) to assess the reliability of RCT findings. This article refers to Cook S, Liu X, Hancock M, et al. How robust is the evidence for prehabilitation in cancer surgery? A systematic review and fragility index analysis. Ann Surg Oncol. 2025. In press. ([https://doi.org/10.1245/s10434-025-18138-3](https://doi.org/10.1245/s10434-025-18138-3)). © The Author(s) 2025 First Received: 16 September 2025 Accepted: 26 September 2025 Published online: 9 October 2025 D. Steffens, PhD [e-mail: daniel.steffens@health.nsw.gov.au](e-mail: daniel.steffens@health.nsw.gov.au) PRESENT A recent systematic review5 analyzed 76 RCTs evaluating the impact of prehabilitation on postoperative outcomes for patients undergoing thoracic, abdominal, and pelvic cancer surgeries. Across these trials, 544 postoperative complication outcomes were reported, yet only 25 were statistically significant. More concerning, the findings showed that the evidence supporting prehabilitation is fragile. In most cases, changing the outcome of just one patient could negate a statistically significant result (FI of 1), and changing the outcomes of four patients could render a non-significant result statistically significant (RFI of 4). Additionally, 64 % of the studies were assessed as having a high risk of bias, further undermining the reliability of the evidence base. FUTURE Robust scientific evidence should withstand small variations in outcomes to ensure confidence in clinical decisionmaking. Unfortunately, the current body of RCTs investigating prehabilitation in cancer surgery lacks this robustness. Given that minimal changes in patient outcomes can alter statistical significance, clinicians should be cautious about relying solely on these trials to guide practice. To address these limitations, future research should prioritize methodologic rigor and larger sample sizes. Additionally, researchers should incorporate comprehensive outcome assessment approaches

FAQs

What is the key concern raised about prehabilitation evidence in cancer surgery?

The reflection suggests the evidence from randomized trials is statistically fragile and may change with minimal outcome variation in a small number of patients.

How do the fragility index (FI) and reverse fragility index (RFI) inform the assessment?

FI and RFI quantify how many patient outcome changes are needed to shift statistical significance. The reflection reports FI of 1 in many cases and RFI of 4 in others.

What future research steps are recommended to strengthen the evidence?

Future work should prioritize methodological rigor and larger sample sizes, incorporate clinically meaningful outcome assessments, and extend fragility analysis to Enhanced Recovery After Surgery (ERAS) trials.

Sep 29, 2026

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