Prognostic factors for non‑metastatic castration‑resistant prostate cancer treated with androgen receptor signaling inhibitors

Takahara,Kiyoshi; Naiki,Taku; Nakane,Keita; Watanabe,Hiromitsu; Miyake,Hideaki; Koie,Takuya; Yasui,Takahiro; Shiroki,Ryoichi

doi:10.3892/mco.2024.2772

Prognostic factors for non‑metastatic castration‑resistant prostate cancer treated with androgen receptor signaling inhibitors

Authors:
- Kiyoshi Takahara
- Taku Naiki
- Keita Nakane
- Hiromitsu Watanabe
- Hideaki Miyake
- Takuya Koie
- Takahiro Yasui
- Ryoichi Shiroki
View Affiliations

Affiliations: Department of Urology, Fujita‑Health University, School of Medicine, Toyoake, Aichi 470‑1192, Japan, Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8602, Japan, Department of Urology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan, Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431‑3192, Japan
Published online on: August 8, 2024 https://doi.org/10.3892/mco.2024.2772
Article Number: 74
Copyright: © Takahara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The treatment paradigm for non‑metastatic castration‑resistant prostate cancer (nmCRPC) has changed in recent years. An observational multicenter study was conducted to evaluate the effectiveness of androgen receptor signaling inhibitors (ARSIs) as a first‑line treatment for patients with nmCRPC. The present study included native Japanese patients from four hospitals who received ARSIs as a first‑line treatment for nmCRPC. The primary endpoint of the study was to evaluate the efficacy and safety of ARSI in patients with nmCRPC. The secondary endpoint was to develop a novel system to stratify the prognoses of these patients. In total, 160 patients were included in the present study. Within a median follow‑up period of 23 months, the median overall survival (OS) was not reached, whereas the median progression‑free survival was 26 months. Multivariate Cox regression analyses showed that the time to CRPC, prostate‑specific antigen (PSA) level at the initiation of nmCRPC treatment and Geriatric Nutritional Risk Index (GNRI) were independent predictors of OS. The patients for whom information about all three independent OS predictors was available were subsequently divided into three groups as follows: Group 1, 57 patients with negative or one positive independent OS predictor; group 2, 38 patients with two positive independent OS predictors; and group 3, 10 patients with three independent OS predictors. The OS differed significantly among the three groups (P<0.0001). In conclusion, ARSIs as a first‑line treatment may be associated with favorable outcomes in Japanese patients with nmCRPC. Time to CRPC, PSA level at the initiation of nmCRPC treatment and GNRI are potential predictors of OS in Japanese patients with nmCRPC who received ARSIs as a first‑line treatment.

View Figures

View References

1	Paller CJ and Antonarakis ES: Management of biochemically recurrent prostate cancer after local therapy: Evolving standards of care and new directions. Clin Adv Hematol Oncol. 11:14–23. 2013.PubMed/NCBI
2	Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, Walsh PC and Eisenberger MA: The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: Long-term follow-up. BJU Int. 109:32–39. 2012.PubMed/NCBI View Article : Google Scholar
3	Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, et al: Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 34:1402–1418. 2016.PubMed/NCBI View Article : Google Scholar
4	Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, et al: Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 383:1040–1049. 2020.PubMed/NCBI View Article : Google Scholar
5	Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, et al: Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 378:1408–1418. 2018.PubMed/NCBI View Article : Google Scholar
6	Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, et al: Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 382:2197–206. 2020.PubMed/NCBI View Article : Google Scholar
7	Ryan CJ, Crawford ED, Shore ND, Underwood W III, Taplin ME, Londhe A, Francis PSJ, Phillips J, McGowan T and Kantoff PW: The IMAAGEN study: effect of abiraterone acetate and prednisone on prostate specific antigen and radiographic disease progression in patients with nonmetastatic castration resistant prostate cancer. J Urol. 200:344–352. 2018.PubMed/NCBI View Article : Google Scholar
8	Esther J, Maughan BL, Anderson N, Agarwal N and Hahn AW: Management of nonmetastatic castration-resistant prostate cancer: Recent advances and future direction. Curr Treat Options Oncol. 20(14)2019.PubMed/NCBI View Article : Google Scholar
9	Bouillanne O, Morineau G, Dupont C, Coulombel I, Vincent JP, Nicolis I, Benazeth S, Cynober L and Aussel C: Geriatric nutritional risk index: A new index for evaluating at-risk elderly medical patients. Am J Clin Nutr. 82:777–783. 2005.PubMed/NCBI View Article : Google Scholar
10	Buyyounouski MK, Choyke PL, McKenney JK, Sartor O, Sandler HM, Amin MB, Kattan MW and Lin DW: Prostate cancer-major changes in the American joint committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 67:245–253. 2017.PubMed/NCBI View Article : Google Scholar
11	Lodde M, Lacombe L and Fradet Y: Salvage therapy with bicalutamide 150 mg in nonmetastatic castration-resistant prostate cancer. Urology. 76:1189–1193. 2010.PubMed/NCBI View Article : Google Scholar
12	Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M, Fontana JA, Chapman RA, Mills GM, Raghavan D and Crawford ED: Southwest Oncology Group. Antiandrogen withdrawal in castrate-refractory prostate cancer: A southwest oncology group trial (SWOG 9426). Cancer. 112:2393–2400. 2008.PubMed/NCBI View Article : Google Scholar
13	Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T, Fujii M, Takihana Y, Usui T, Matsuda T, et al: Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol. 180:921–927. 2008.PubMed/NCBI View Article : Google Scholar
14	Tombal B, Sternberg CN, Hussain M, Ganguli A, Li Y, Sandin R, Bhadauria H, Oh M and Saad F: Matching-adjusted indirect treatment comparison of the efficacy of enzalutamide versus apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer. ESMO Open. 7(100510)2022.PubMed/NCBI View Article : Google Scholar
15	Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, et al: Apalutamide and overall survival in prostate cancer. Eur Urol. 79:150–158. 2021.PubMed/NCBI View Article : Google Scholar
16	Howard LE, Moreira DM, De Hoedt A, Aronson WJ, Kane CJ, Amling CL, Cooperberg MR, Terris MK and Freedland SJ: Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int. 120:E80–E86. 2017.PubMed/NCBI View Article : Google Scholar
17	Frees S, Akamatsu S, Bidnur S, Khalaf D, Chavez-Munoz C, Struss W, Eigl BJ, Gleave M, Chi KN and So A: The impact of time to metastasis on overall survival in patients with prostate cancer. World J Urol. 36:1039–1046. 2018.PubMed/NCBI View Article : Google Scholar
18	Miyake H, Matsushita Y, Watanabe H, Tamura K, Motoyama D, Ito T, Sugiyama T and Otsuka A: Prognostic significance of time to castration resistance in patients with metastatic castration-sensitive prostate cancer. Anticancer Res. 39:1391–1396. 2019.PubMed/NCBI View Article : Google Scholar
19	Wenzel M, Preisser F, Hoeh B, Schroeder M, Würnschimmel C, Steuber T, Heinzer H, Banek S, Ahrens M, Becker A, et al: Impact of time to castration resistance on survival in metastatic hormone sensitive prostate cancer patients in the era of combination therapies. Front Oncol. 11(659135)2021.PubMed/NCBI View Article : Google Scholar
20	Okamoto T, Hatakeyama S, Narita S, Takahashi M, Sakurai T, Kawamura S, Hoshi S, Ishida M, Kawaguchi T, Ishidoya S, et al: Impact of nutritional status on the prognosis of patients with metastatic hormone-naive prostate cancer: A multicenter retrospective cohort study in Japan. World J Urol. 37:1827–1835. 2019.PubMed/NCBI View Article : Google Scholar
21	Chang LW, Hung SC, Li JR, Chiu KY, Yang CK, Chen CS, Lu K, Chen CC, Wang SC, Lin CY, et al: Geriatric nutritional risk index as a prognostic marker for patients with metastatic castration-resistant prostate cancer receiving docetaxel. Front Pharmacol. 11(601513)2020.PubMed/NCBI View Article : Google Scholar