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Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

General Review Article

Neoadjuvant Strategies Before Radical Prostatectomy for High Risk Prostate Cancer in the Era of New Hormonal Agents

Author(s): Alessandro Tafuri, Maria Angela Cerruto and Alessandro Antonelli*

Volume 22 , Issue 1 , 2021

Published on: 21 June, 2020

Page: [68 - 76] Pages: 9

DOI: 10.2174/1389450121666200621194409

Price: $65


Prostate cancer (PCa) is a hormone-dependent disease, including several different patterns from indolent and clinically meaningless to aggressive and lethal disease. Among non -metastatic PCa, high-risk disease represents a therapeutical challenge, given the unfavorable oncological outcomes after exclusive local therapy. Deprivation therapy in the neoadjuvant setting is not recommended prior to radical prostatectomy since it did not provide any survival advantage, although reducing tumor volume, surgical margins rate, local and nodal stage. However, in the few recent years, new hormonal treatments for metastatic PCa emerged and showed a relevant increase of overall survival concerning standard androgen deprivation therapy (ADT). Thus, neo-adjuvant regimens of ADT based on these novel molecules are now under investigation and the results of ongoing clinical trials are expected in order to provide a definitive answer on the real role of neoadjuvant hormonal therapy in the treatment of high-risk localized prostate cancer. In this narrative review, we underline the role of neoadjuvant therapy before radical prostatectomy in high-risk PCa patients considering the impact of the new available hormonal agents.

Keywords: Prostate cancer, neoadjuvant therapy, radical prostatectomy, new hormonal agents, abiraterone, enzalutamide, apalutamide.

Graphical Abstract
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
[] [PMID: 30620402]
D’Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280(11): 969-74.
[] [PMID: 9749478]
Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71(4): 618-29.
[] [PMID: 27568654]
Mohler JL, Antonarakis ES, Armstrong AJ, et al. Prostate cancer, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2019; 17(5): 479-505.
[] [PMID: 31085757]
Sanda MG, Cadeddu JA, Kirkby E, et al. Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part I: risk stratification, shared decision making, and care options. J Urol 2018; 199(3): 683-90.
[] [PMID: 29203269]
Johnston TJ, Shaw GL, Lamb AD, et al. ProtecT study group. Mortality among men with advanced prostate cancer excluded from the ProtecT trial. Eur Urol 2017; 71(3): 381-8.
[] [PMID: 27720537]
Bandini M, Fossati N, Gandaglia G, et al. Neoadjuvant and adjuvant treatment in high-risk prostate cancer. Expert Rev Clin Pharmacol 2018; 11(4): 425-38.
[] [PMID: 29355037]
Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason M. Neo‐adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database of Systematic Reviews 2006; (4):
Hu J, Xu H, Zhu W, et al. Neo-adjuvant hormone therapy for non-metastatic prostate cancer: a systematic review and meta-analysis of 5,194 patients. World J Surg Oncol 2015; 13(1): 73.
[] [PMID: 25884478]
Pignot G, Maillet D, Gross E, et al. Systemic treatments for high-risk localized prostate cancer. Nat Rev Urol 2018; 15(8): 498-510.
[] [PMID: 29765147]
Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 1972; 22(4): 232-40.
[] [PMID: 4625049]
Porcaro AB, Tafuri A, Sebben M, et al. High body mass index predicts multiple prostate cancer lymph node metastases after radical prostatectomy and extended pelvic lymph node dissection. Asian J Androl 2020; 22(3): 323-9.
[] [PMID: 31347517]
Fujita K, Nonomura N. Role of androgen receptor in prostate cancer: a review. World J Mens Health 2019; 37(3): 288-95.
[] [PMID: 30209899]
Fair WR, Cookson MS, Stroumbakis N, et al. The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results. Urology 1997; 49(3A)(Suppl.): 46-55.
[] [PMID: 9123736]
Isaacs JT, Coffey DS. Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res 1981; 41(12 Pt 1): 5070-5.
[PMID: 7307008]
Antonelli A, Palumbo C, Veccia A, et al. Biological effect of neoadjuvant androgen-deprivation therapy assessed on specimens from radical prostatectomy: a systematic review. Minerva Urol Nefrol 2018; 70(4): 370-9.
[] [PMID: 29392925]
Porcaro AB, De Luyk N, Corsi P, et al. Clinical factors predicting bilateral lymph node invasion in high-risk prostate cancer. clinical factors predicting bilateral lymph node invasion in high-risk prostate cancer. Urol Int 2017; 99(4): 392-9.
[] [PMID: 28486228]
Antonelli A, Palumbo C, Berruti A. Neoadjuvant androgen deprivation therapy through intense inhibition of the androgen target:“Midsummer Night’s Dream” or “Much Ado About Nothing”? Annals of translational medicine 2019; 7(Suppl. 6)2019. : 76.
Schulman CC, Sassine AM. Neoadjuvant hormonal deprivation before radical prostatectomy. Eur Urol 1993; 24(4): 450-5.
[] [PMID: 7507045]
Solomon MH, McHugh TA, Dorr RP, Lee F, Siders DB. Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy. Clin Invest Med 1993; 16(6): 532-8.
[PMID: 8013157]
Soloway MS, Sharifi R, Wajsman Z, McLeod D, Wood DPJ Jr, Puras-Baez A. the lupron depot neoadjuvant prostate cancer study group. Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. J Urol 1995; 154(2 Pt 1): 424-8.
[] [PMID: 7541859]
Soloway MS, Hachiya T, Civantos F, Murphy WM, Gomez CC, Ruiz HE. Androgen deprivation prior to radical prostatectomy for T2b and T3 prostate cancer. Urology 1994; 43(2)(Suppl.): 52-6.
[] [PMID: 7509535]
Kennedy TJ, Sonneland AM, Marlett MM, Troup RH. Luteinizing hormone-releasing hormone downstaging of clinical stage C prostate cancer. J Urol 1992; 147(3 Pt 2): 891-3.
[] [PMID: 1371563]
Oesterling JE, Andrews PE, Suman VJ, Zincke H, Myers RP. Preoperative androgen deprivation therapy: artificial lowering of serum prostate specific antigen without downstaging the tumor. J Urol 1993; 149(4): 779-82.
[] [PMID: 7681117]
Aprikian AG, Fair WR, Reuter VE, et al. Experience with neoadjuvant diethylstilboestrol and radical prostatectomy in patients with locally advanced prostate cancer. Br J Urol 1994; 74(5): 630-6.
[] [PMID: 7530128]
Labrie F, Cusan L, Gomez J-L, et al. Neoadjuvant hormonal therapy: the Canadian experience. Urology 1997; 49(3A)(Suppl.): 56-64.
[] [PMID: 9123738]
Selli C, Montironi R, Bono A, et al. PROSIT Study Group. Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer. J Clin Pathol 2002; 55(7): 508-13.
[] [PMID: 12101195]
Soloway MS, Pareek K, Sharifi R, et al. Lupron depot neoadjuvant prostate cancer study group. Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. J Urol 2002; 167(1): 112-6.
[] [PMID: 11743286]
Aus G, Abrahamsson PA, Ahlgren G, et al. Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial. BJU Int 2002; 90(6): 561-6.
[] [PMID: 12230618]
Klotz LH, Goldenberg SL, Jewett MA, et al. Canadian Uro-Oncology Group. Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J Urol 2003; 170(3): 791-4.
[] [PMID: 12913699]
Yee DS, Lowrance WT, Eastham JA, Maschino AC, Cronin AM, Rabbani F. Long-term follow-up of 3-month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial. BJU Int 2010; 105(2): 185-90.
[] [PMID: 19594741]
Tosco L, Laenen A, Briganti A, et al. The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer. Prostate Cancer Prostatic Dis 2017; 20(4): 407-12.
[] [PMID: 28485390]
Mellado B, Font A, Alcaraz A, et al. Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer. Br J Cancer 2009; 101(8): 1248-52.
[] [PMID: 19755998]
Eastham JAG, Heller S, Halabi JP, Monk H, Beltran M. Gleave. LBA-12 CALGB 90203 (ALLIANCE): radical prostatectomy with or without neoadjuvant chemohormonal therapy in men with clinically localized, high risk prostate cancer. The Journal of Urology 2019; 2014: e997-7.
Monfette G. Temporary combination therapy with Flutamide and Tryptex as adjuvant to radical prostatectomy for the treatment of early stage prostate cancer Early stage prostate cancer: Diagnosis and choice of therapy 1989.
Chun J, Pruthi RS. Is neoadjuvant hormonal therapy before radical prostatectomy indicated? Urol Int 2004; 72(4): 275-80.
[] [PMID: 15153722]
Fair WR, Aprikian AG, Cohen D, Sogani P, Reuter V. Use of neoadjuvant androgen deprivation therapy in clinically localized prostate cancer. Clin Invest Med 1993; 16(6): 516-22.
[PMID: 8013156]
Macfarlane MT, Abi-Aad A, Stein A, Danella J, Belldegrun A, deKernion JB. Neoadjuvant hormonal deprivation in patients with locally advanced prostate cancer. J Urol 1993; 150(1): 132-4.
[] [PMID: 7685421]
Oberlin DT, Flum AS, Lai JD, Meeks JJ. The effect of minimally invasive prostatectomy on practice patterns of American urologists. Urologic Oncology: Seminars and Original Investigations Elsevier 2016.
Student S, Hejmo T, Poterała-Hejmo A, Leśniak A, Bułdak R. Anti-androgen hormonal therapy for cancer and other diseases. Eur J Pharmacol 2020.866172783
[] [PMID: 31712062]
Taplin M-E, Montgomery B, Logothetis CJ, et al. Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. J Clin Oncol 2014; 32(33): 3705-15.
[] [PMID: 25311217]
Efstathiou E, Davis JW, Titus MA, Chapin bf, Zurita AJ, Wen S, et al. Neoadjuvant enzalutamide (ENZA) and abiraterone acetate (AA) plus leuprolide acetate (LHRHa) versus AA+ LHRHa in localized high-risk prostate cancer (LHRPC). J ournal of Clinical Oncology 2016; 3415: 5002-2.
Montgomery B, Tretiakova MS, Joshua AM, et al. Neoadjuvant Enzalutamide Prior to Prostatectomy. Clin Cancer Res 2017; 23(9): 2169-76.
[] [PMID: 28151719]
McKay RR, Ye H, Xie W, et al. Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone. J Clin Oncol 2019; 37(11): 923-31.
[] [PMID: 30811282]
Joshua AM, Fleshner NE, Chin J, Emmenegger U, Gleave ME, Hotte SJ, et al. Abiraterone+/-cabazitaxel in defining complete response in prostatectomy (ACDC-RP) trial. JAmerican Society of Clinical Oncology 2017.
Marchioni M, Sountoulides P, Bada M, et al. Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies. Ther Adv Urol 2018; 10(10): 305-15.
[] [PMID: 30186368]
Jung ME, Ouk S, Yoo D, et al. Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC). J Med Chem 2010; 53(7): 2779-96.
[] [PMID: 20218717]
Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009; 324(5928): 787-90.
[] [PMID: 19359544]
Alkhudair NA. Apalutamide: Emerging Therapy for Non-Metastatic Castration-Resistant Prostate Cancer. Saudi Pharm J 2019; 27(3): 368-72.
[] [PMID: 30976180]

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