Yaşlı kas invaziv mesane kanseri hastalarında mesane koruyucu trimodal tedavi: tek merkez gerçek yaşam deneyimi

Öz

Amaç: Bu çalışmada, erken evre kas invaziv mesane kanseri (MIBC) tanısı almış ve trimodal tedavi (TMT) uygulanmış ileri yaşlı hasta grubunda, gerçek yaşam verileri kullanılarak sağkalım sonuçları ile prognostik belirteçlerin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Bu retrospektif analizde, yaş ortalaması 70 olan ve evre T2N0–T2N1 MIBC tanısı alarak TMT (maksimal transüretral rezeksiyon, kemoterapi ve radyoterapi) uygulanmış 23 hasta değerlendirilmiştir. Genel sağkalım (OS) ve progresyonsuz sağkalım (PFS) Kaplan-Meier yöntemiyle hesaplanmış; prognostik faktörler çok değişkenli Cox regresyon analiziyle incelenmiştir. Ayrıca, PLR ve NLR gibi sistemik inflamatuar belirteçlerin prognostik rolü de değerlendirilmiştir. Bulgular: Ortanca OS süresi 22 ay (%95 GA: 12,5–31,5), ortanca PFS süresi ise 19 ay (%95 GA: 14,5–47,4) olarak hesaplanmıştır. Platin bazlı kemoterapi uygulanan hastalarda OS anlamlı şekilde daha uzun bulunmuştur (HR: 0,041; p = 0,015). Yüksek PLR ve ileri N evresi OS ile negatif yönde ilişkili bulunmuştur. PFS açısından anlamlı bir değişken saptanmamış olmakla birlikte, T evresindeki artış sağkalımda azalma eğilimi göstermiştir. Radyoterapi dozunun sağkalım üzerinde anlamlı bir etkisi gözlenmemiştir. Sonuç: Bu çalışma, komorbiditesi yüksek yaşlı MIBC hastalarında TMT’nin etkin ve tolere edilebilir bir tedavi seçeneği olduğunu göstermektedir. Platin temelli rejimlerin sağkalım avantajı sağladığı; PLR ve nodal evrenin ise potansiyel prognostik belirteçler olarak öne çıktığı belirlenmiştir. Kabul edilebilir toksisite oranları ve sağkalım verileri göz önünde bulundurulduğunda, TMT yaşlı bireyler için mesane koruyucu umut verici bir alternatif olarak değerlendirilmelidir.

Anahtar Kelimeler

• kas invaziv mesane tümörü
• trimodal tedavi
• yaşlı hasta

Etik Beyan

The study protocol was approved by the Ethics Committee of the University of Health Sciences, Gülhane Faculty of Medicine (Approval No: 2025/192, dated April 8, 2025).

Bladder-sparing trimodal therapy in elderly patients with muscle-invasive bladder cancer: a real-world single-center experience

Öz

Aim: This study aimed to evaluate survival outcomes and potential prognostic indicators in a real-world cohort of elderly patients diagnosed with early-stage muscle-invasive bladder cancer (MIBC) who underwent trimodal therapy (TMT). Material and Methods: This retrospective study included 23 patients with a mean age of 70 years diagnosed with stage T2N0–T2N1 MIBC and treated with TMT, which comprised maximal transurethral resection, chemotherapy, and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and the impact of clinical and laboratory variables on survival was assessed through multivariable Cox regression analysis. Inflammatory biomarkers such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were also evaluated for their prognostic significance. Results: The median OS was 22 months (95% CI: 12.5–31.5), and the median PFS was 19 months (95% CI: 14.5–47.4). Patients receiving platinum-based chemotherapy had significantly improved OS (HR: 0.041; p = 0.015). Higher platelet-to-lymphocyte ratio (PLR) and advanced nodal stage (N stage) were negatively associated with OS. Although no factor was significantly associated with PFS, a trend toward decreased survival was observed with increasing T stage. Radiotherapy dose did not have a significant impact on survival outcomes. Conclusion: This study highlights the efficacy and tolerability of TMT in elderly, comorbid patients with early-stage MIBC who are candidates for bladder preservation. Platinum-based regimens appear to confer a survival advantage, while PLR and nodal stage may serve as practical prognostic markers. Given the acceptable survival outcomes and favorable toxicity profile, TMT should be considered a promising bladder-sparing option for appropriately selected elderly patients.

Anahtar Kelimeler

• urinary bladder neoplasms
• combined modality therapy
• aged

Etik Beyan

The study protocol was approved by the Ethics Committee of the University of Health Sciences, Gülhane Faculty of Medicine (Approval No: 2025/192, dated April 8, 2025).

Kaynakça

1. Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström PU, Choi W et al. Bladder cancer. Lancet 2016; 388: 2796-810.
2. Compérat E, Larré S, Rouprêt M, Neuzillet Y, Houédé N, Roy C et al. Current best practice for bladder cancer: a narrative review of diagnostics and treatments. Lancet 2022; 400: 1712-21.
3. Ramakrishnan VM, Eswara JR. The timing of radical cystectomy following neoadjuvant chemotherapy. Transl Androl Urol 2018; 7(Suppl 6): S758-62.
4. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kübler H et al. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol 2018; 36: 43-53.
5. Ploussard G, Daneshmand S, Efstathiou JA, Herr HW, James ND, Rodel CM et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. Eur Urol 2014; 66: 120-37.
6. Vashistha V, Wang H, Mazzone A, Bandyopadhyay D, Gupta A, Dynda D et al. Radical cystectomy compared to combined modality treatment for muscle-invasive bladder cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys 2017; 97:1002-20.
7. Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols. J Clin Oncol 2014; 32: 3801-9.
8. James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012; 366: 1477-88.

9. Wang SJ. Trimodality therapy in the modern era for management of bladder cancer. Transl Cancer Res 2024; 13: 3935-45.
10. Turgeon GA, Souhami L. Trimodality therapy for bladder preservation in the elderly population with invasive bladder cancer. Front Oncol 2014; 4: 206.
11. Coen JJ, Zhang P, Saylor PJ, Lee CT, Wu CL, Parker W et al. Bladder preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712—a randomized phase II trial. J Clin Oncol 2019; 37: 44-51.
12. Aluwini S, Pos F, Schimmel E, Krol S, van der Voort van Zyp J, Moonen L et al. Bladder function preservation with brachytherapy, external beam radiation therapy, and limited surgery in bladder cancer patients: long-term results. Int J Radiat Oncol Biol Phys 2014; 88: 611-7.
13. Giacalone NJ, Shipley WU, Clayman RH, Niemierko A, Drumm M, Heney NM et al. Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the Massachusetts General Hospital experience. Eur Urol 2017; 71: 952-60.
14. Lawrence TS, Blackstock AW, McGinn C. The mechanism of action of radiosensitization of conventional chemotherapeutic agents. Semin Radiat Oncol 2003; 13: 13-21.
15. Hall E, Hussain SA, Porta N, Lewis R, Birtle AJ, Nicholson S et al. Chemoradiotherapy in muscle-invasive bladder cancer: 10-yr follow-up of the phase 3 randomised controlled BC2001 trial. Eur Urol 2022; 82: 273-9.
16. Miyamoto DT, Mouw KW, Harshman LC, Niemierko A, Drumm MR, Wu CL et al. Outcomes and tolerability of selective bladder preservation by combined modality therapy for invasive bladder cancer in elderly patients. Int J Radiat Oncol Biol Phys 2017; 99(2 Suppl): S120.
17. Zlotta AR, Lajkosz K, Efstathiou JA. Radical cystectomy vs trimodality therapy for muscle-invasive bladder cancer: further extensive evaluation needed – Authors' reply. Lancet Oncol 2023; 24: e325-6.
18. Black AJ, Zargar H, Zargar-Shoshtari K, Fairey AS, Mertens LS, Dinney CP et al. The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy. Urol Oncol 2020; 38: 77.e11-9.
19. Chen H, Chen H, Liang L, Liu J, Wang J, Gao Y et al. The clinicopathological and prognostic value of NLR, PLR and MLR in non-muscular invasive bladder cancer. Arch Esp Urol 2022; 75: 467-71.
20. Bizzarri FP, Di Meo S, Zamparella C, Pecoraro M, Merola R, Pierconti F et al. Prognostic Value of PLR, SIRI, PIV, SII, and NLR in Non-Muscle Invasive Bladder Cancer: Can Inflammatory Factors Influence Pathogenesis and Outcomes? Cancers (Basel) 2025; 17: 2189.
21. Hurmuz P, Bozkurt O, Keskin S, Kucukarda A, Bilici A, Oksuzoglu B. Gemcitabine based trimodality treatment in patients with muscle invasive bladder cancer: May neutrophil lymphocyte and platelet lymphocyte ratios predict outcomes? Urol Oncol 2021; 39: 370.e9-15.
22. Karl A, Carroll PR, Gschwend JE, Knuchel R, Montorsi F, Stenzl A et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol 2009; 55: 826-35.
23. Wang X, Ni X, Tang G. Prognostic role of platelet-to-lymphocyte ratio in patients with bladder cancer: a meta-analysis. Front Oncol 2019; 9: 757.
24. Jo Y, Yuk HD. Trimodal therapy in the treatment of muscle-invasive bladder cancer. J Urol Oncol 2024; 22: 256-67.
25. Mak RH, Hunt D, Shipley WU, Tester WJ, Hagan MP, Kaufman DS et al. Long-term outcomes in patients with muscle-invasive bladder cancer after bladder-preserving combined-modality therapy: a pooled analysis of RTOG protocols. J Clin Oncol 2012; 30(5 Suppl): 264.
26. Song YP, Choudhury A, Nelson M, Hoskin P, James ND. Long-term outcomes of radical radiation therapy with hypoxia modification with biomarker discovery for stratification: 10-year update of the BCON phase 3 randomized trial. Int J Radiat Oncol Biol Phys 2021; 110: 1407-15.
27. Choudhury A, Porta N, Hall E, Song Y, Bahl A, Parmar M, et al. Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials. Lancet Oncol 2021; 22: 246-55.
28. Kobayashi K, Saito Y, Kawai K, Takahashi R, Yoshino T, Otsuka H et al. The efficacy of trimodal chemoradiotherapy with gemcitabine and cisplatin as a bladder-preserving strategy for the treatment of muscle-invasive bladder cancer: a single-arm phase II study. Jpn J Clin Oncol 2022; 52: 1201-7.
29. Weickhardt A, Tan A, Yip S, Kichenadasse G, McKendrick J, Lawrentschuk N et al. Pembrolizumab with chemoradiation as treatment for muscle-invasive bladder cancer: analysis of safety and efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502). Eur Urol Oncol 2024; 7: 469-77.