PURPOSE: The aim of this study was to investigate the oncologic efficacy of combining docetaxel with androgen deprivation therapy (ADT) versus nonsteroidal antiandrogen (NSAA) with ADT in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with focus on the effect of sequential therapy in a real-world clinical practice setting. METHODS: The records of 382 patients who harbored high-volume mHSPC, based on the CHAARTED criteria, and had received ADT with either docetaxel (n = 92) or NSAA (bicalutamide) (n = 290) were retrospectively analyzed. The cohorts were matched by one-to-one propensity scores based on patient demographics. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), and time to second-line progression (PFS2) were compared. 2nd-line PFS defined as the time from CRPC diagnosis to progression after second-line therapy was also compared. RESULTS: After matching, a total of 170 patients were retained: 85 patients treated with docetaxel + ADT and 85 patients treated with NSAA + ADT. The median OS and CSS for docetaxel + ADT versus NSAA + ADT were not reached (NR) vs. 49 months (p = 0.02) and NR vs. 55 months (p = 0.02), respectively. Median time to CRPC and PFS2 in patients treated with docetaxel + ADT was significantly longer compared to those treated with NSAA (22 vs. 12 months; p = 0.003 and, NR vs. 28 months; p < 0.001, respectively). There was no significant difference in 2nd-line PFS between the two groups. CONCLUSIONS: Our analysis suggested that ADT with docetaxel significantly prolonged OS and CSS owing to a better time to CRPC and PFS2 in comparison to NSAA + ADT in high-volume mHSPC.

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 3 19 18 Nishi shimbashi Minato ku Tokyo 105 8471 Japan

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

Department of Urology Weill Cornell Medical College New York NY 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

Zobrazit více v PubMed

Schaeffer E, Srinivas S, Antonarakis ES, Armstrong AJ, Bekelman JE, Cheng H, et al. NCCN guidelines insights: prostate cancer, version 1202.1. J Natl Compr Canc Netw. 2021;19(2):134–43. doi: 10.6004/jnccn.2021.0008. PubMed DOI

Yamaoka M, Hara T, Kusaka M. Overcoming persistent dependency on androgen signaling after progression to castration-resistant prostate cancer. Clin Cancer Res. 2010;16(17):4319–24. doi: 10.1158/1078-0432.CCR-10-0255. PubMed DOI

Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737–46. doi: 10.1056/NEJMoa1503747. PubMed DOI PMC

James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–77. doi: 10.1016/S0140-6736(15)01037-5. PubMed DOI PMC

Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, 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):263–82. doi: 10.1016/j.eururo.2020.09.046. PubMed DOI

Maximum androgen blockade in advanced prostate cancer An overview of the randomised trials. Prost Cancer Trialists' Collabo Group Lancet. 2000;355(9214):1491–1498. PubMed

Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998;339(15):1036–42. doi: 10.1056/NEJM199810083391504. PubMed DOI

Goebell PJ, Shah R, Raina R, Rege S, Chen SL, Lee VE, et al. Real-world treatment patterns in metastatic hormone-sensitive prostate cancer (mHSPC) patients in the US, Germany, France. China Japan Ann Oncol. 2021;32:S660–S661. doi: 10.1016/j.annonc.2021.08.1136.PubMedPMID:WOS:000700527701089. DOI

Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate canCER. N Engl J Med. 2019;381(2):121–31. doi: 10.1056/NEJMoa1903835. PubMed DOI

Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, 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. doi: 10.1093/annonc/mdz396. PubMed DOI PMC

Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, 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):1080–7. doi: 10.1200/JCO.2017.75.3657. PubMed DOI PMC

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45(2):228–47. doi: 10.1016/j.ejca.2008.10.026. PubMed DOI

Soloway MS, Hardeman SW, Hickey D, Raymond J, Todd B, Soloway S, et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer-Am Cancer Soc. 1988;61(1):195–202. PubMed

Oronsky B, Carter CA, Reid TR, Scicinski J, Oronsky A, Lybeck M, 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):716–22. doi: 10.1016/j.neo.2015.09.001. PubMed DOI PMC

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):150–61. doi: 10.1002/pst.433. PubMed DOI PMC

Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med. 2013;32(16):2837–2849. doi: 10.1002/sim.5705.PubMedPMID:23239115;PubMedCentralPMCID:PMCPMC3747460. PubMed DOI PMC

Gravis G, Boher JM, Joly F, Soulie M, Albiges L, Priou 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):256–62. doi: 10.1016/j.eururo.2015.11.005. PubMed DOI

Teoh JYC, Poon DMC, Lam D, Chan T, Chan MFT, Lee EKC, et al. A territory-wide, multicenter, age- and prostate-specific antigen-matched study comparing chemohormonal therapy and hormonal therapy alone in chinese men with metastatic hormone-sensitive prostate cancer. Clin Genitourin Cancer. 2019;17(1):e203–e8. doi: 10.1016/j.clgc.2018.10.010. PubMed DOI

Francini E, Yip S, Ahmed S, Li H, Ardolino L, Evan CP, et al. Clinical outcomes of first-line abiraterone acetate or enzalutamide for metastatic castration-resistant prostate cancer after androgen deprivation therapy + docetaxel or ADT alone for metastatic hormone-sensitive prostate cancer. Clin Genitourin Cancer. 2018;16(2):130–4. doi: 10.1016/j.clgc.2017.12.012. PubMed DOI PMC

Tsaur I, Heidegger I, van den Bergh RCN, Bektic J, Borgmann H, Foti S, et al. Treatment of metastasized prostate cancer beyond progression after upfront docetaxel-a real-world data assessment. Eur Urol Focus. 2020 doi: 10.1016/j.euf.2020.06.018. PubMed DOI

Martini A, Pfail J, Montorsi F, Galsky MD, Oh WK. Surrogate endpoints for overall survival for patients with metastatic hormone-sensitive prostate cancer in the CHAARTED trial. Prostate Cancer Prostatic Dis. 2020;23(4):638–45. doi: 10.1038/s41391-020-0231-5. PubMed DOI

Frees S, Akamatsu S, Bidnur S, Khalaf D, Chavez-Munoz C, Struss W, et al. The impact of time to metastasis on overall survival in patients with prostate cancer. World J Urol. 2018;36(7):1039–46. doi: 10.1007/s00345-018-2236-4. PubMed DOI

Miyake H, Matsushita Y, Watanabe H, Tamura K, Motoyama D, Ito T, et al. Prognostic significance of time to castration resistance in patients with metastatic castration-sensitive prostate cancer. Anticancer Res. 2019;39(3):1391–6. doi: 10.21873/anticanres.13253. PubMed DOI

Hatakeyama S, Narita S, Takahashi M, Sakurai T, Kawamura S, Hoshi S, et al. Association of tumor burden with the eligibility of upfront intensification therapy in metastatic castration-sensitive prostate cancer: a multicenter retrospective study. Int J Urol. 2020;27(7):610–7. doi: 10.1111/iju.14258. PubMed DOI

Mori K, Janisch F, Mostafaei H, Lysenko I, Karakiewicz PI, Enikeev DV, et al. Prognostic value of hemoglobin in metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis. Clin Genitourin Cancer. 2020;18(4):e402–e9. doi: 10.1016/j.clgc.2019.12.002. PubMed DOI

Mori K, Janisch F, Parizi MK, Mostafaei H, Lysenko I, Enikeev DV, et al. Prognostic value of alkaline phosphatase in hormone-sensitive prostate cancer: a systematic review and meta-analysis. Int J Clin Oncol. 2020;25(2):247–57. doi: 10.1007/s10147-019-01578-9. PubMed DOI PMC

Mori K, Kimura T, Onuma H, Kimura S, Yamamoto T, Sasaki H, et al. Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer. Prostate. 2017;77(10):1144–50. doi: 10.1002/pros.23373. PubMed DOI

Yanagisawa T, Kimura T, Mori K, Suzuki H, Sano T, Otsuka T, et al. Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer. Prostate. 2021 doi: 10.1002/pros.24243. PubMed DOI

Naito S, Tsukamoto T, Koga H, Harabayashi T, Sumiyoshi Y, Hoshi S, et al. Docetaxel plus prednisolone for the treatment of metastatic hormone-refractory prostate cancer: a multicenter phase II trial in Japan. Jpn J Clin Oncol. 2008;38(5):365–72. doi: 10.1093/jjco/hyn029. PubMed DOI

Armstrong AJ, Iguchi T, Azad AA, Szmulewitz RZ, Holzbeierlein J, Villers A, et al. Final overall survival (OS) analysis from ARCHES: a phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) Ann Oncol. 2021;32:S1300–S1301. doi: 10.1016/j.annonc.2021.08.2101.PubMedPMID:WOS:000700527703500. DOI

Chi KN, Chowdhury S, Bjartell A, Chung BH, de Santana P, Gomes AJ, Given R, 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):2294–303. doi: 10.1200/JCO.20.03488. PubMed DOI

Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, 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. doi: 10.1016/S1470-2045(19)30082-8. PubMed DOI