Castration resistant prostate cancer: from existing therapies to compounds under investigation


  • Raveena Bajaj Medical Affairs and Clinical Research, Ipca Laboratories Ltd., Mumbai, Maharashtra, India
  • Anil Pareek Medical Affairs and Clinical Research, Ipca Laboratories Ltd., Mumbai, Maharashtra, India
  • Indranil Purkait Medical Affairs and Clinical Research, Ipca Laboratories Ltd., Mumbai, Maharashtra, India



Metastatic, Advanced prostate cancer, CRPC, Guidelines


Prostate carcinoma is a highly prevalent biologically and clinically heterogeneous disease. Unfortunately, within 5 years of diagnosis, 10-20% of patients acquire a castration-resistant prostate cancer (CRPC) in spite of multiple surgical and non-surgical therapy choices. The clinical context of CRPC is heterogeneous, encompassing patients with asymptomatic prostate-specific antigen (PSA) elevation following ADT failure and good performance status, as well as those experiencing severe, incapacitating symptoms and a rapidly progressing disease that ultimately results in death. Non-metastatic CRPC (nmCRPC) is a stage of the disease that is transient and is defined by certain criteria that are set within a certain time frame. Most patients with nmCRPC will eventually develop metastatic lesions, which are linked to morbidity and death specific to prostate cancer. Until 2010, the only treatments for patients with metastatic prostate cancer were androgen deprivation therapy and docetaxel. The advent of several hormonal and non-hormonal therapies such as abiraterone acetate, enzalutamide, apalutamide, cabazitaxel, darolutamide, the immunotherapeutic sipuleucel-T has brought about a paradigm shift in management of CRPC patients. These molecules have demonstrated a survival benefit in mCRPC & nmCRPC. For patients with advanced PSMA-positive mCRPC, 177Lu-PSMA-617 radioligand therapy offers a novel and efficacious therapeutic approach. PARPi are sensitive to tumors with gene mutations that impact homologous recombination repair, such as BRCA1 and BRCA2 abnormalities in mCRPC. The goal of this study was to highlight recent developments in CRPC clinical trials as well as guidelines recommendations for CRPC.



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.

SEER stat fact sheets: prostate cancer. Available at: Accessed on 23 September 2021.

Congregado RB, Rivero BI, Lendínez CG, Medina LRA. Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy. Biomedicines. 2023;11(4):1105.

Mottet N, Cornford P. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. European urology 2023. Available at: guidelines/prostate-cancer. Accessed on 20 November 2023.

Lowrance W, Dreicer R, Jarrard DF, Scarpato KR, Kim SK, Kirkby E, et al. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023). J Urol. 2023;209(6):1082-90.

Saad F, Aprikian A, Finelli A, Fleshner NE, Gleave M, Kapoor A, et al. 2022 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) guideline: Management of castration-resistant prostate cancer (CRPC). Canad Urol Assoc J. 2022;16(11):E506.

Edward A. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. 2023;4:1459.

Ryan CJ, Smith MR, Fizazi K. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152-60.

Beer TM, Armstrong AJ, Rathkopf D. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study. Eur Urol. 2017;71: 151-4.

Nadal R, Taplin M-E, Bellmunt J. Enzalutamide for the treatment of prostate cancer: results and implications of the AFFIRM trial. Future Oncol. 2014;10:351-62.

Petrylak DP, Tangen CM, Hussain MHA. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513-20.

De Bono JS, Oudard S, Ozguroglu M. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147-54.

Kantoff PW, Higano CS, Shore ND. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-22.

Parker C, Nilsson S, Heinrich D. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213-23.

Al‐Mansouri L, Gurney H. Clinical concepts for cabazitaxel in the management of metastatic castration‐resistant prostate cancer. Asia‐Pacific J Clin Oncol. 2019;15(6):288-95.

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. New Eng J Med. 2018;378(26):2465-74.

Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. New Eng J Med. 2018;378(15):1408-18.

Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. New Eng J Med. 2019;380(13):1235-46.

Ryan CJ, Crawford ED, Shore ND, Underwood W, Taplin ME, Londhe A, et al. 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. 2018;200(2):344-52.

Wang L, Paller C, Hong H, Rosman L, De Felice A, Brawley O, et al. Comparison of treatments for nonmetastatic castration-resistant prostate cancer: matching-adjusted indirect comparison and network meta-analysis. JNCI. 2022;114(2):191-202.

Congregado B, Rivero I, Osmán I, Sáez C, Medina López R. PARP inhibitors: a new horizon for patients with prostate cancer. Biomedicines. 2022;10(6):1416.

Ferretti S, Mercinelli C, Marandino L, Litterio G, Marchioni M, Schips L. Metastatic Castration-Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs. Res Rep Urol. 2023:243-59.

Liu X, Fang GC, Lu H, Shi ZD, Chen ZS, Han CH. Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Drugs Today. 2023;59(1):37-49.

Nabavi N, Mahdavi SR, Ardalan MA, Chamanara M, Mosaed R, Lara A, et al. Bipolar Androgen Therapy: When Excess Fuel Extinguishes the Fire. Biomedicines. 2023;11(7):2084.

Denmeade SR, Sena LA, Wang H, Antonarakis ES, Markowski MC. Bipolar Androgen Therapy followed by androgen receptor inhibition as sequential therapy for prostate cancer. Oncologist. 2023;28(6):465-73.

Markowski MC, Wang H, De Marzo AM, Schweizer MT, Antonarakis ES, Denmeade SR. Clinical efficacy of bipolar androgen therapy in men with metastatic castration-resistant prostate cancer and combined tumor-suppressor loss. Eur Urol Open Sci. 2022;41: 112-5.

Markowski MC, Wang H, Sullivan R, Rifkind I, Sinibaldi V, Schweizer MT, et al. A multicohort open-label phase II trial of bipolar androgen therapy in men with metastatic castration-resistant prostate cancer (RESTORE): a comparison of post-abiraterone versus post-enzalutamide cohorts. Eur Urol. 2021; 79(5):692-9.

You X, Huang S, Wang XA, Yi C, Gong N, Yu J, et al. Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review. Front Endocrinol. 2023;13:1125838.

Morris MJ, Heller G, Hillman DW, Bobek O, Ryan C, Antonarakis ES, et al. Randomized phase III study of enzalutamide compared with enzalutamide plus abiraterone for metastatic castration-resistant prostate cancer (Alliance A031201 trial). J Clin Oncol. 2023; 41(18):3352-62.

Shiota M, Inoue R, Tashiro K, Kobayashi K, Horiyama S, Kanji H, et al. A Phase II trial of abiraterone with dutasteride for second‐generation antiandrogen‐and chemotherapy‐naïve patients with castration‐resistant prostate cancer. J Clin Pharmacol. 2023;63(4):445-54.

Gillessen S, Procopio G, Hayoz S, Kremer E, Schwitter M, Caffo O, et al. Darolutamide maintenance in patients with metastatic castration-resistant prostate cancer with nonprogressive disease after taxane treatment (SAKK 08/16). J Clin Oncol. 2023;41(20):3608.

Zhou T, Qin S, Xu W, Tang S, Chen G, Li S, et al. Proxalutamide in metastatic castration‐resistant prostate cancer: Primary analysis of a multicenter, randomized, open‐label, phase 2 trial. Int J Cancer. 2023.

Omlin A, Cathomas R, von Amsberg G, Reuter C, Feyerabend S, Loidl W, et al. Randomized Phase II Cabazitaxel Dose Individualization and Neutropenia Prevention Trial in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2023;29(10):1887-93.

de Wit R, Freedland SJ, Oudard S, Marinov G, Capart P, Combest AJ, et al. Real-world evidence of patients with metastatic castration-resistant prostate cancer treated with cabazitaxel: comparison with the randomized clinical study CARD. Prostate Cancer Prostatic Dis. 2023;26(1):67-73.

Yang ES, Halabi S, Rothe M, Garrett-Mayer E, Mangat PK, Pisick E, et al. Olaparib in Patients With Metastatic Prostate Cancer With BRCA1/2 Mutation: Results From the TAPUR Study. JCO Precis Oncol. 2023;7:e2200505.

Kim JW, McKay RR, Radke MR, Zhao S, Taplin ME, Davis NB, et al. Randomized trial of olaparib with or without cediranib for metastatic castration-resistant prostate cancer: The results from national cancer institute 9984. J Clin Oncol. 2023;41(4):871.

Pan E, Xie W, Ajmera A, Araneta A, Jamieson C, Folefac E, et al. A phase I study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases (COMRADE). Mol Cancer Therap. 2023;22(4):511-8.

Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-51.

Quinn Z, Leiby B, Sonpavde G, Choudhury AD, Sweeney C, Einstein D, et al. Phase I study of niraparib in combination with radium-223 for the treatment of metastatic castrate-resistant prostate cancer. Clin Cancer Res. 2023;29(1):50-9.

Abida W, Campbell D, Patnaik A, Bryce AH, Shapiro J, Bambury RM, et al. Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study. Eur Urol. 2023.

Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023.

Bögemann M, Shore ND, Smith MR, Tammela TL, Ulys A, Vjaters E, et al. Efficacy and safety of darolutamide in patients with nonmetastatic castration-resistant prostate cancer stratified by prostate-specific antigen doubling time: Planned subgroup analysis of the phase 3 ARAMIS trial. Eur Urol. 2023;83(3):212-21.

Madan RA, Bilusic M, Stein MN, Donahue RN, Arlen PM, Karzai F, et al. Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer. Oncologist. 2023.

Carles J, Medina-Lopez RA, Puente J, Gómez-Ferrer Á, Nebra JC, Sáez Medina MI, et al. Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis. Future Oncol. 2023;19(12):819-28.

De La Cerda J, Dunshee C, Gervasi L, Sieber P, Belkoff L, Tutrone R, et al. A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer. Target Oncol. 2023;15:1-8.

Pollock Y, Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik B, et al. Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide. Prostate Cancer Prostatic Dis. 2023; 26(1):156-61.




How to Cite

Bajaj, R., Pareek, A., & Purkait, I. (2024). Castration resistant prostate cancer: from existing therapies to compounds under investigation. International Journal of Research in Medical Sciences, 12(3), 1014–1022.



Review Articles