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Locally advanced mid/low rectal cancer with synchronous resectable liver metastases: systematic review of the available strategies and outcome

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Abstract

The management of patients with locally advanced mid/low rectal cancer with resectable liver metastases is complex because of the need to combine the optimal treatment of both tumors. This study aims to review the available treatment strategies and compare their outcome, focusing on radiotherapy (RT) and liver-first approach (LFA). A systematic review was performed in PubMed, Embase, and web sources including articles published between 2000 and 02/2023 and reporting mid-/long-term outcomes. Overall, twenty studies were included (n = 1837 patients). Three- and 5-year overall survival (OS) rates were 51–88% and 36–59%. Although several strategies were reported, most patients received RT (1448/1837, 79%; > 85% neoadjuvant). RT reduced the pelvic recurrence risk (5.8 vs. 13.5%, P = 0.005) but did not impact OS. Six studies analyzed LFA (n = 307 patients). LFA had a completion rate similar to the rectum-first approach (RFA, 81% vs. 79%) but the interval strategy—an LFA variant with liver surgery in the interval between radiotherapy and rectal surgery—had a better completion rate than standard LFA (liver surgery/radiotherapy/rectal surgery, 92% vs. 75%, P = 0.011) and RFA (79%, P = 0.048). Across all series, LFA achieved the best survival rates, and in one paper it led to a survival advantage in patients with multiple metastases. In conclusion, different strategies can be adopted, but RT should be included to decrease the pelvic recurrence risk. LFA should be considered, especially in patients with high hepatic tumor burden, and RT before liver surgery (interval strategy) could maximize its completion rate.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge Prof. F. Calise and Prof. P. Miccoli, coordinators of the Medical Writing course “Light into a Scientific Paper” of the SIC (Italian Society of Surgery) which was held in Rome in October 2022. They had the merit to create this cooperative group of researchers and to address and mentor their activity.

Standards of reporting

The systematic review was carried out according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Funding

The present study was funded by the AIRC (Italian Association for Cancer Research) Grant #2019− 23822 (PI: Prof. Luca Viganò).The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Author notes

  1. R. Tutino, A. Bonomi, and C. C. Zingaretti equally contributed to the manuscript (co-first authors).

  2. M. Paterno and I. Pezzoli equally contributed to the manuscript (co-last authors).

Authors and Affiliations

  1. Department of General and Emergency Surgery, AOU Città della Salute e della Scienza di Torino, Turin, Italy

    R. Tutino

  2. Department of General Surgery, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, Milan, Italy

    A. Bonomi

  3. General Surgery Residency Program, University of Milan, Milan, Italy

    A. Bonomi, M. Paterno & I. Pezzoli

  4. Department of Digestive and Hepatobiliary Surgery, Mauriziano Umberto I Hospital, Turin, Italy

    C. C. Zingaretti

  5. Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy

    L. Risi, E. M. Ragaini & L. Viganò

  6. Hepatobiliary Unit, Department of Minimally Invasive General and Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125, Bergamo, Italy

    L. Risi & L. Viganò

  7. Division of Oncologic and Minimally Invasive Surgery, Niguarda General Hospital, Milan, Italy

    M. Paterno

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Contributions

Conceptualization: R Tutino, A Bonomi, CC Zingaretti, M Paterno, I Pezzoli; Methodology: Vigano’ L; Data collection: R Tutino, A Bonomi, CC Zingaretti, L Risi, E M Ragaini, M Paterno, I Pezzoli; Formal analysis and investigation: All authors; Writing—original draft: R Tutino, A Bonomi, CC Zingaretti, L Risi, M Paterno, I Pezzoli; Writing: review and editing: E M Ragaini, L Viganò; Final approval: all authors.

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Correspondence to L. Viganò.

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Viganò L: received speaker’s honoraria from Johnson & Johnson. The remaining authors: reported no biomedical financial interests or potential conflicts of interest.

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The present study complies with the guidelines for human studies. The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. No Institutional Review Board approval was required (Review article).

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Tutino, R., Bonomi, A., Zingaretti, C.C. et al. Locally advanced mid/low rectal cancer with synchronous resectable liver metastases: systematic review of the available strategies and outcome. Updates Surg 76, 345–361 (2024). https://doi.org/10.1007/s13304-023-01735-w

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