PURPOSE: We aimed to assess the oncologic efficacy of combining docetaxel (DOC) versus abiraterone (ABI) with androgen deprivation therapy (ADT) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC), with a focus on the efficacy of sequential therapy, in a real-world clinical practice setting. METHODS: The records of 336 patients who harbored de novo high-risk mHSPC, based on the LATITUDE criteria, and had received ADT with either DOC (n = 109) or ABI (n = 227) were retrospectively analyzed. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), time to 2nd-line progression (PFS2), and 2nd- and 3rd-line PFS, were compared. We used one-to-two propensity score matching to minimize the confounders. The differential efficacy of 2nd-line therapy based on agents in each arm was evaluated using the unmatched cohort as an additional interest. RESULTS: After propensity score matching, 86 patients treated with DOC + ADT and 172 with ABI + ADT were available for analyses. The 3-year OS and CSS for DOC versus ABI were 76.2% versus 75.1% (p = 0.8) and 78.2% versus 78.6% (p = 1), respectively. There was no difference in the median PFS2 (49 vs. 43 months, p = 0.39), while the median time to CRPC in patients treated with ABI was significantly longer compared to those treated with DOC (42 vs. 22 months; p = 0.006). The median 2nd-line PFS (14 vs. 4 months, p < 0.001) and 3rd-line PFS (4 vs. 2 months, p = 0.012) were significantly better in the DOC group than in the ABI group. Among the unmatched cohort, after ABI for mHSPC, the median 2nd-line PFS did not differ between the patients treated with DOC and those treated with enzalutamide as 2nd-line therapy (both 3 months, p = 0.8). CONCLUSIONS: ADT with DOC or ABI has comparable oncologic outcomes in terms of OS, CSS, and PFS2 in patients with de novo high-risk mHSPC. Compared to DOC, ABI resulted in longer time to CRPC but worse 2nd and 3rd-line PFS. Further studies are needed to clarify the optimal sequence of therapy in the upfront intensive treatment era.

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Akita University School of Medicine Akita Japan

Department of Urology Atsugi City Hospital Kanagawa Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Division of Advanced Blood Purification Therapy Hirosaki University Graduate School of Medicine Aomori Japan

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University of Texas Southwestern Medical Center Dallas Texas USA

Department of Urology Weill Cornell Medical College New York New York USA

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

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Schaeffer E, Srinivas S, Antonarakis ES, et al. NCCN guidelines insights: prostate cancer, version 1.2021. J National Comprehensive Cancer Net. 2021;19(2):134-143.

Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: a randomized, phase iii study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37(32):2974-2986.

Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24.

Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2):121-131.

Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700.

Gravis G, Boher JM, Joly F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016;70(2):256-262.

Hoyle AP, Ali A, James ND, et al. Abiraterone in “high-” and “low-risk” metastatic hormone-sensitive prostate cancer. Eur Urol. 2019;76(6):719-728.

Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080-1087.

Mori K, Mostafaei H, Sari Motlagh R, et al. Systemic therapies for metastatic hormone-sensitive prostate cancer: network meta-analysis. BJU Int. 2022;129(4):423-433. doi:10.1111/bju.15507

Sathianathen NJ, Koschel S, Thangasamy IA, et al. Indirect comparisons of efficacy between combination approaches in metastatic hormone-sensitive prostate cancer: a systematic review and network meta-analysis. Eur Urol. 2020;77(3):365-372.

Wang L, Paller CJ, Hong H, De Felice A, Alexander GC, Brawley O. Comparison of systemic treatments for metastatic castration-sensitive prostate cancer: a systematic review and network meta-analysis. Jama Oncol. 2021;7(3):412-420. doi:10.1001/jamaoncol.2020.6973

Wang Y, Gui H, Wang J, et al. Comparative efficacy of combined radiotherapy, systemic therapy, and androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a network meta-analysis and systematic review. Front Oncol. 2020;10:567616.

Sydes MR, Spears MR, Mason MD, et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018;29(5):1235-1248.

Narita S, Kimura T, Hatakeyama S, et al. Real-world outcomes and risk stratification in patients with metastatic castration-sensitive prostate cancer treated with upfront abiraterone acetate and docetaxel. Int J Clin Oncol. 2022;27:1477-1486.

Narita S, Kimura T, Hatakeyama S, et al. Real-world survival outcomes of adding docetaxel or abiraterone in patients with high-volume metastatic castration-sensitive prostate cancer: historically controlled, propensity score matched comparison with androgen deprivation therapy. World J Urol. 2022;40(5):1135-1141.

Clarke NW, Ali A, Ingleby FC, et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019;30(12):1992-2003.

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.

Soloway MS, Hardeman SW, Hickey D, et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer. 1988;61(1):195-202.

Oronsky B, Carter CA, Reid TR, et al. Confirmatory trials in the evaluation of anticancer medicinal products in man-PFS2: a measure of therapeutic action-at-a-distance. Neoplasia. 2015;17(9):716-722.

Cornford P, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. Part II-2020 update: treatment of relapsing and metastatic prostate cancer. Eur Urol. 2021;79(2):263-282.

Yanagisawa T, Kimura T, Hata K, et al. Combination of docetaxel versus nonsteroidal antiandrogen with androgen deprivation therapy for high-volume metastatic hormone-sensitive prostate cancer: a propensity score-matched analysis. World J Urol. 2022. doi:10.1007/s00345-022-04030-2

Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28(25):3083-3107.

Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011;10(2):150-161.

Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med. 2013;32(16):2837-2849.

James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338-351.

Azad AA, Armstrong AJ, Alcaraz A, et al. Efficacy of enzalutamide in subgroups of men with metastatic hormone-sensitive prostate cancer based on prior therapy, disease volume, and risk. Prostate Cancer Prostatic Dis. 2022; 25(2):274-282. doi:10.1038/s41391-021-00436-y

Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303.

Menges D, Yebyo HG, Sivec-Muniz S, et al. Treatments for metastatic hormone-sensitive prostate cancer: systematic review, network meta-analysis, and benefit-harm assessment. Eur Urol Oncol. 2022; 5(6):605-616. doi:10.1016/j.euo.2022.04.007

Rush HL, Murphy L, Morgans AK, et al. Quality of life in men with prostate cancer randomly allocated to receive docetaxel or abiraterone in the STAMPEDE trial. J Clin Oncol. 2022;40(8):825-836.

Pelloux-Prayer R, Schiele P, Oudard S, et al. Cost-effectiveness analysis of innovative therapy for patients with newly diagnosed hormone-sensitive metastatic prostate cancer. Clin Genitourin Cancer. 2021;19(5):e326-e333.

Pelloux-Prayer R, Bataillard T, Thiery-Vuillemin A, Vincent A, Fagnoni P, Nerich V. Treatment of patients with metastatic hormone-sensitive prostate cancer: a systematic review of economic evaluations. Clin Genitourin Cancer. 2022;20(6):594-602. doi:10.1016/j.clgc.2022.04.014

Sung WWY, Choi HCW, Luk PHY, So TH. A cost-effectiveness analysis of systemic therapy for metastatic hormone-sensitive prostate cancer. Front Oncol. 2021;11:627083.

Khalaf DJ, Chen L, Sunderland K, et al. Treatment outcomes for metastatic castration-resistant prostate cancer (mCRPC) following progression on upfront androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPI) for metastatic castration-sensitive prostate cancer (mCSPC). J Clin Oncol. 2022;40(6_suppl):60.

Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022;399(10336):1695-1707.

Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386:1132-1142.

Yanagisawa T, Rajwa P, Thibault C, et al. Androgen receptor signaling inhibitors in addition to docetaxel with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis. Eur Urol. 2022;82(6):584-598. doi:10.1016/j.eururo.2022.08.002

Saad F, Armstrong AJ, Thiery-Vuillemin A, et al. PROpel: phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2022;40(6_suppl):11.