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Generalizability of Randomized Controlled Trials in Rectal Cancer

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

The generalizability of outcomes from randomized controlled trials (RCTs) in oncology is a frequent concern. Given the prevalence and multidisciplinary management of rectal cancer, understanding the generalizability of rectal cancer RCTs is critical to surgical oncologists.

Methods

An exhaustive literature review identified 100 non-metastatic rectal cancer RCTs published in English over the past 10 years investigating surgery, chemotherapy, or radiotherapy. In order to evaluate the representativeness of these RCTs compared to the USA and each continent’s rectal cancer populations, demographic characteristics were stratified by surgical versus chemoradiotherapy (CRT) trial and by continent then compared with the National Cancer Database and CANCER TODAY using chi-squared and Welch’s t-tests.

Results

Of the 100 trials identified, 65% enrolled significantly younger patients, and 38% enrolled a significantly greater proportion of males than the US rectal cancer population. These demographic differences were more prominent among CRT trials than surgical trials. Half of all trials enrolled patients who were on average more than 7 years younger and enrolled a 5% greater proportion of males than their respective continental rectal cancer populations. Patients enrolled in trials had more advanced cancers than their corresponding continental populations. Sociodemographic data was rarely reported.

Conclusion

Patients enrolled in trials were younger, predominantly male, and had advanced stage cancer when compared to the rectal cancer population. Sociodemographic variables are underreported, further limiting equal participation in clinical trials. Future rectal cancer RCTs should strive to recruit representative samples. To enhance recruitment of women and underrepresented minorities, tailored recruitment strategies must be implemented.

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Author information

Authors and Affiliations

  1. Surgical Health Outcomes & Research Enterprise, Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA

    Shawn Hsu, Katherine J. Rosen, Larissa Temple & Fergal Fleming

  2. Community Outreach & Engagement, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA

    AnaPaula Cupertino

Authors
  1. Shawn Hsu
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  2. Katherine J. Rosen
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  3. AnaPaula Cupertino
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  4. Larissa Temple
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  5. Fergal Fleming
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Contributions

Dr. Shawn Hsu contributed to the design and drafting of the work as well as the acquisition, analysis, and interpretation of the data. Dr. Katherine Rosen contributed to the acquisition and interpretation of the data as well as revisions for important intellectual content. Dr. AnaPaula Cupertino contributed to the interpretation of the data and revisions for important intellectual content. Dr. Larissa Temple contributed to the design and interpretation of the work as well as providing important revisions. Dr. Fergal Fleming contributed to the conception of the work, interpretation of the data, and revisions of important intellectual content. The final draft was approved by all authors, and all authors agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Shawn Hsu.

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Conflict of Interest

Dr. Fergal Fleming has received payments from UpToDate for his contributions to a chapter on surgical approach in open abdominoperineal resection. Dr. Larissa Temple has received grants from the Agency for Healthcare Research and Quality for the spreading and dissemination of electronic patient reported outcomes and also has a grant from the Patient-Centered Outcomes Research Institute. The remaining authors have no conflicts of interest or grants to disclose.

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Appendices

Appendix 1

Preliminary Search

9/5/20:

PubMed Search: 402.

Rectal Neoplasms [MeSH Terms] AND (y_10[Filter]) AND (randomizedcontrolledtrial[Filter]).

Title/Abstract reviewed. Categorized by surgical vs non-surgical, outcomes of interest, general topic, and grouped by same RCTs.

Search Strategy

Search completed on 9/22/20.

EMBASE: 972 results.

#1 (“rectal neoplasms”/exp OR “rectal carcinoma”:ab,ti OR “rectal adenocarcinoma”:ab,ti OR “rectal cancer”:ab,ti OR “rectal tumors”:ab,ti OR “rectal tumours”:ab,ti OR “rectal neoplasms”:ab,ti OR ((rectal or rectum) NEAR/3 (carcinoma OR adenocarcinoma OR cancer OR tumors OR tumours OR neoplasms)):ab,ti) NOT (metastatic:ab,ti OR metastasis:ab,ti OR screening:ti OR colorectal:ti OR colon:ab,ti OR anal:ab,ti OR anus:ab,ti).

#2 #1 NOT “conference abstract”/it.

#3 #2 AND [randomized controlled trial]/lim AND [2010–2020]/py.

PubMed/MEDLINE: 422.

(“rectal neoplasms”[MeSH Terms] OR “rectal cancer” [tiab] OR “rectal carcinoma” [tiab] OR “rectal adenocarcinoma” [tiab] OR “rectal tumors” [tiab] OR “rectal tumours” [tiab] OR “rectal neoplasms” [tiab] OR ((rectal [tiab] OR rectum [tiab]) AND (cancer [tiab] OR carcinoma [tiab] OR adenocarcinoma [tiab] OR tumors [tiab] OR tumours [tiab] OR neoplasms [tiab]))) NOT (colon [tiab] OR anal [tiab] OR anus [tiab] OR colorectal [ti] OR metastatic [tiab] OR metastasis [tiab] OR screening[ti]).

Filtered by:

  • Randomized controlled trial

  • Publication date from 2010 to 2020

  • English language

Cochrane Library: 1996.

#1 MeSH descriptor: [Rectal Neoplasms] explode all trees.

#2 (“rectal carcinoma”:ab,ti OR “rectal adenocarcinoma”:ab,ti OR “rectal cancer”:ab,ti OR “rectal tumors”:ab,ti OR “rectal tumours”:ab,ti OR “rectal neoplasms”:ab,ti OR ((rectal or rectum) NEAR/3 (carcinoma OR adenocarcinoma OR cancer OR tumors OR tumours OR neoplasms)):ab,ti).

#3 metastatic:ab,ti OR metastasis:ab,ti OR screening:ti OR colorectal:ti OR colon:ab,ti OR anal:ab,ti OR anus:ab,ti.

#4 (#1 OR #2) NOT #3

Limits: Publication Year from 2010 to 2020, in Trials.

EBSCO CINAHL: 254

((MH “Colorectal Neoplasms + ”) OR AB (“rectal cancer” OR “rectal carcinoma” OR “rectal neoplasms” OR “rectal tumors” OR “rectal tumours” OR ((rectal OR rectum) N3 (cancer OR carcinoma OR neoplasms OR tumors OR tumours)) OR TI (“rectal cancer” OR “rectal carcinoma” OR “rectal neoplasms” OR “rectal tumors” OR “rectal tumours” OR ((rectal OR rectum) N3 (cancer OR carcinoma OR neoplasms OR tumors OR tumours))))) NOT (TI metastatic OR TI metastasis OR TI screening OR TI colorectal OR TI colon OR TI anal OR TI anus OR AB metastatic OR AB metastasis OR AB colon OR AB anal OR AB anus).

Filtered by:

  • English language

  • Publication type: randomized controlled trial

  • Published date: 2010–2020

Inclusion/Exclusion Criteria

Inclusion Criteria

  • Published in English

  • Published from 2010 to 2020

  • Randomized controlled trial

  • Rectal cancer only

  • Study intervention involves the following:

    • Chemotherapy (differences in regimens or timing of regimens)

    • Radiotherapy (differences in regimens or timing of regimens)

    • Surgical therapy (differences in timing of surgery after neoadjuvant therapy or main portions of surgery during primary resection)

      • Main portion: tumor resection, colorectal or coloanal reconstruction, or diverting ileostomy creation

    • Combination of the above

  • Study primary or secondary outcomes involved:

    • Oncologic outcomes (e.g., overall survival, disease free survival, or tumor response)

    • Surgical outcomes (e.g., complications, resection margins, or mortality)

Exclusion Criteria

  • Metastatic or recurrent disease

  • Pilot studies

  • Pooled analyses

  • Interim results

  • Studies drawing on data from over 20 years ago

Appendix 2

Table 2 Summary of rectal cancer RCTs
Full size table

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Hsu, S., Rosen, K.J., Cupertino, A. et al. Generalizability of Randomized Controlled Trials in Rectal Cancer. J Gastrointest Surg 26, 453–465 (2022). https://doi.org/10.1007/s11605-021-05192-x

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  • DOI: https://doi.org/10.1007/s11605-021-05192-x

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