Impact of Preoperative Sarcopenia on Perioperative Complications and Functional Outcomes, and Biochemical Recurrence Following Radical Prostatectomy: Single-Institution Experience, Retrospective Cohort Study

Abstract

Objective: Sarcopenia is increasingly recognized as a marker of frailty and a predictor of adverse outcomes in surgical oncology. However, its role in patients undergoing radical prostatectomy (RP) for localized prostate cancer (PCa) remains unclear.
Methods: We retrospectively analyzed 165 men who underwent RP between 2015 and 2025 at a single institution. Sarcopenia was assessed using preoperative CT-derived skeletal muscle index (SMI). Perioperative complications, pathological outcomes, urinary continence, erectile function, biochemical recurrence (BCR), and all-cause mortality (ACM) were com-pared between sarcopenic and non-sarcopenic patients. Statistical analyses included the Mann–Whitney U test, chi-square test, Kaplan–Meier analysis with the log-rank test, and Cox proportional hazards regression.
Results: Of the cohort, 75 patients (45.5%) were sarcopenic. These patients were older (median age 69 vs. 66 years, p=0.005) and had higher comorbidity scores (CCI ≥5: 56.0% vs. 32.2%, p=0.002). Major complications (Clavien-Dindo ≥3) occurred more frequently in the sarcopenic group (10.7% vs. 1.1%, p=0.007), although no perioperative mortality was observed. Continence status at 12 months was comparable between the groups (p=0.373). IIEF-5 scores were lower in sarcopenic patients at 12 months (median, 10 vs. 12; p=0.021); however, baseline IIEF-5 scores also differed significantly between the groups. During a median follow-up of 37 months, 65 patients developed BCR and 11 died (7 sarcopenic). Cumulative incidence of biochemical recurrence was 44% at the median follow-up. Although sarcopenic patients showed a higher recurrence trend (≈65% vs. 37%), no statistically significant difference was observed (p=0.267). In Cox Regression analysis, sarcopenia did not appear to significantly predict BCR (HR 0.75, 95% CI 0.45–1.24, p=0.272).
Conclusions: Preoperative sarcopenia may be associated with increased major perioperative complications and impaired erectile function following RP. However, it was not significantly associated with BCR in this cohort. Sarcopenia may primarily serve as an indicator of surgical vulnerability rather than oncological prognosis.

Keywords

• Biochemical recurrence
• Prostate cancer
• Radical prostatectomy
• Sarcopenia

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. doi:10.3322/caac.21660.
2. Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on prostate cancer-2024 update. part I: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2024;86(2):148-63. doi:10.1016/j.eururo.2024.03.027.
3. Ficarra V, Novara G, Rosen RC, Artibani W, Carroll PR, Costello A, et al. Systematic review and meta-analysis of studies reporting urinary continence recovery after robot-assisted radical prostatectomy. Eur Urol. 2012;62(3):405-17. doi:10.1016/j.eururo.2012.05.045.
4. Markowski MC, Chen Y, Feng Z, Cullen J, Trock BJ, Suzman D, et al. PSA doubling time and absolute PSA predict metastasis-free survival in men with biochemically recurrent prostate cancer after radical prostatectomy. Clin Genitourin Cancer. 2019;17(6):470-5.e1. doi:10.1016/j.clgc.2019.08.002.
5. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31. doi:10.1093/ageing/afy169. Erratum in: Age Ageing. 2019 Jul 1;48(4):601. doi:10.1093/ageing/afz046.
6. Psutka SP, Carrasco A, Schmit GD, Moynagh MR, Boorjian SA, Frank I, et al. Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer-specific and all-cause mortality. Cancer. 2014;120(18):2910-8. doi:10.1002/cncr.28798.
7. Joglekar S, Nau PN, Mezhir JJ. The impact of sarcopenia on survival and complications in surgical oncology: a review of the current literature. J Surg Oncol. 2015;112(5):503-9. doi:10.1002/jso.24025.
8. Jahrreiss V, Laukhtina E, D'Andrea D, Shariat SF. The prognostic value of sarcopenia in patients with prostate cancer: a systematic review. Curr Opin Urol. 2021;31(4):315-23. doi:10.1097/MOU.0000000000000885.

9. Pak S, Park SY, Shin TJ, You D, Jeong IG, Hong JH, et al. Association of muscle mass with survival after radical prostatectomy in patients with prostate cancer. J Urol. 2019;202(3):525-32. doi:10.1097/JU.0000000000000249.
10. Mason RJ, Boorjian SA, Bhindi B, Rangel L, Frank I, Karnes RJ, et al. The association between sarcopenia and oncologic outcomes after radical prostatectomy. Clin Genitourin Cancer. 2018;16(3):e629-36. doi:10.1016/j.clgc.2017.11.003.
11. Angerer M, Salomon G, Beyersdorff D, Fisch M, Graefen M, Rosenbaum CM. Impact of sarcopenia on functional and onco-logical outcomes after radical prostatectomy. Front Surg. 2021;7:620714. doi:10.3389/fsurg.2020.620714.
12. Chang AJ, Autio KA, Roach M 3rd, Scher HI. High-risk prostate cancer-classification and therapy. Nat Rev Clin Oncol. 2014;11(6):308-23. doi:10.1038/nrclinonc.2014.68.
13. Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013;31(12):1539-47. doi:10.1200/JCO.2012.45.2722.
14. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11(6):319-26. doi:10.1038/sj.ijir.3900472.
15. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-13. doi:10.1097/01.sla.0000133083.54934.ae.
16. Mitsui Y, Sadahira T, Watanabe T, Araki M, Maruyama Y, Sato R, et al. Correlation between lumbar skeletal muscle size and urinary incontinence after radical prostatectomy. Low Urin Tract Symptoms. 2020;12(3):245-52. doi:10.1111/luts.12312.
17. Kovač MB, Pavlin T, Čavka L, Ribnikar D, Spazzapan S, Templeton AJ, et al. The trajectory of sarcopenia following diagnosis of prostate cancer: a systematic review and meta-analysis. J Geriatr Oncol. 2023;14(7):101594. doi:10.1016/j.jgo.2023.101594.
18. Mitsui Y, Sadahira T, Maruyama Y, Sato R, Rodrigo AGH, Wada K, et al. Impact of sarcopenia on erectile function after nerve-sparing robot-assisted radical prostatectomy. World J Mens Health. 2021;39(4):673-82. doi:10.5534/wjmh.200036.
19. Aluganti Narasimhulu C, Singla DK. Amelioration of diabetes-induced inflammation mediated pyroptosis, sarcopenia, and adverse muscle remodelling by bone morphogenetic protein-7. J Cachexia Sarcopenia Muscle. 2021;12(2):403-20. doi:10.1002/jcsm.12662.
20. Ma W, Zhang R, Huang Z, Zhang Q, Xie X, Yang X, et al. PQQ ameliorates skeletal muscle atrophy, mitophagy and fiber type transition induced by denervation via inhibition of the inflammatory signaling pathways. Ann Transl Med. 2019;7(18):440. doi:10.21037/atm.2019.08.101.
21. Zhao T, Mao W, Hu M, Yu Q, Peng X, Ji J, et al. Advances in sarcopenia and urologic disorders. Front Nutr. 2024;11:1475977. doi:10.3389/fnut.2024.1475977.
22. Laufer M, Perelman M, Sarfaty M, Itelman E, Segal G. Low alanine aminotransferase, as a marker of sarcopenia and frailty, is associated with shorter survival among prostate cancer patients and survivors: a retrospective cohort analysis of 4064 patients. Eur Urol Open Sci. 2023;55:38-44. doi:10.1016/j.euros.2023.07.007.
23. de Pablos-Rodríguez P, Del Pino-Sedeño T, Infante-Ventura D, de Armas-Castellano A, Ramírez Backhaus M, Ferrer JFL, et al. Prognostic impact of sarcopenia in patients with advanced prostate carcinoma: a systematic review. J Clin Med. 2022;12(1):57. doi:10.3390/jcm12010057.
24. Smith MR, Saad F, Egerdie B, Sieber PR, Tammela TL, Ke C, et al. Sarcopenia during androgen-deprivation therapy for prostate cancer. J Clin Oncol. 2012;30(26):3271-6. doi:10.1200/JCO.2011.38.8850.
25. Hara N, Ishizaki F, Saito T, Nishiyama T, Kawasaki T, Takahashi K. Decrease in lean body mass in men with prostate cancer receiving androgen deprivation therapy: mechanism and biomarkers. Urology. 2013;81(2):376-80. doi:10.1016/j.urology.2012.10.050.
26. Bylow K, Mohile SG, Stadler WM, Dale W. Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review. Cancer. 2007;110(12):2604-13. doi:10.1002/cncr.23084.
27. Bargiota A, Oeconomou A, Zachos I, Samarinas M, L Pisters L, Tzortzis V. Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on muscle and bone health. J BUON. 2020;25(3):1286-94. PMID: 32862568.
28. Meyer HJ, Wienke A, Surov A. CT-defined low-skeletal muscle mass as a prognostic marker for survival in prostate cancer: a systematic review and meta-analysis. Urol Oncol. 2022;40(3):103.e9-16. doi:10.1016/j.urolonc.2021.08.009.
29. Chiang PK, Tsai WK, Chiu AW, Lin JB, Yang FY, Lee J. Muscle loss during androgen deprivation therapy is associated with higher risk of non-cancer mortality in high-risk prostate cancer. Front Oncol. 2021;11:722652. doi:10.3389/fonc.2021.722652.
30. Rhee H, Navaratnam A, Oleinikova I, Gilroy D, Scuderi Y, Heathcote P, Nguyen T, et al. A novel liver-targeted testosterone therapy for sarcopenia in androgen deprived men with prostate cancer. J Endocr Soc. 2021;5(9):bvab116. doi:10.1210/jendso/bvab116.
31. Zhang H, Ke Z, Dong S, Du Y, Tang W, Chen M, et al. Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice. Front Pharmacol. 2022;13:1018480. doi:10.3389/fphar.2022.1018480.
32. Lopez P, Newton RU, Taaffe DR, Winters-Stone K, Galvão DA, Buffart LM. Moderators of resistance-based exercise programs' effect on sarcopenia-related measures in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis. J Geriatr Oncol. 2023;14(5):101535. doi:10.1016/j.jgo.2023.101535.
33. Campbell KL, Zadravec K, Bland KA, Chesley E, Wolf F, Janelsins MC. The effect of exercise on cancer-related cognitive impairment and applications for physical therapy: systematic review of randomized controlled trials. Phys Ther. 2020;100(3):523-42. doi:10.1093/ptj/pzz090.
34. Stangl-Kremser J, Mari A, Lai LY, Lee CT, Vince R, Zaslavsky A, et al. Sarcopenic obesity and its prognostic impact on urological cancers: a systematic review. J Urol. 2021;206(4):854-865. doi:10.1097/JU.0000000000001873.
35. McDonald AM, Swain TA, Mayhew DL, Cardan RA, Baker CB, Harris DM, et al. CT measures of bone mineral density and muscle mass can be used to predict noncancer death in men with prostate cancer. Radiology. 2017;282(2):475-83. doi:10.1148/radiol.2016160626.
36. Yossepowitch O, Briganti A, Eastham JA, Epstein J, Graefen M, Montironi R, et al. Positive surgical margins after radical prostatectomy: a systematic review and contemporary update. Eur Urol. 2014;65(2):303-13. doi:10.1016/j.eururo.2013.07.039.
37. Boorjian SA, Karnes RJ, Viterbo R, Rangel LJ, Bergstralh EJ, Horwitz EM, et al. Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer. 2011;117(13):2883-91. doi:10.1002/cncr.25900.