Peri-Adjuvant Androgen Deprivation Therapy for Patients with High-Risk Prostate Cancer Undergoing Radical Prostatectomy – The Concept Behind and Initial Outcomes
Main Article Content
Abstract
Background: Radical prostatectomy (RP) is increasingly employed as part of a multimodal strategy for treating locally advanced and/or high-risk prostate cancer (LA-HR CaP), though its oncological adequacy alone is limited due to the risk of micrometastatic disease. While androgen deprivation therapy (ADT) with radiation remains the traditional standard, the optimal integration of ADT with RP is yet to be defined. This study introduces the concept of periadjuvant ADT, which combines neoadjuvant ADT, RP, and adjuvant ADT for a total duration of 18 months.
Methods: A retrospective study was conducted on 127 patients with LA-HR CaP who received neoadjuvant ADT (Degarelix ± Abiraterone/Apalutamide) for 3–6 months, followed by RP and continuation of ADT postoperatively. Treatment regimens were individualized based on patient preference and affordability. Data were collected on clinical, operative, pathological, and follow-up parameters. Kaplan-Meier analysis was used for survival outcomes.
Results: The majority (67.7%) of patients were staged as T3, with nodal involvement in 26%. Neoadjuvant therapy was well tolerated, with no significant intraoperative complications (99.2% complication-free). Positive surgical margins and nodal positivity were seen in 24.4% and 26.8% of patients, respectively. Adjuvant radiation was required in 29.1% of cases. At a median follow-up of 12 months, overall survival was 97.6%, with a cumulative Kaplan-Meier survival rate of 94.6%.
Conclusion: Periadjuvant ADT combining neoadjuvant and adjuvant hormonal therapy with RP is a feasible and safe approach for LA-HR CaP in a resource-limited setting. Early results suggest acceptable surgical morbidity and promising short-term oncological outcomes. Longer follow-up is warranted to evaluate survival benefits and refine treatment duration guidelines.
Article Details
How to Cite
SAKTHIVEL, Deerush Kannan et al.
Peri-Adjuvant Androgen Deprivation Therapy for Patients with High-Risk Prostate Cancer Undergoing Radical Prostatectomy – The Concept Behind and Initial Outcomes.
Medical Research Archives, [S.l.], v. 13, n. 4, apr. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6497>. Date accessed: 15 may 2025.
doi: https://doi.org/10.18103/mra.v13i4.6497.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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3. Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243-262. doi:10.1016/j.eururo.2020.09.042
4. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388
5. Meng MV, Elkin EP, Latini DM, Duchane J, Carroll PR. Treatment of Patients With High Risk Localized Prostate Cancer: Results From Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE). J Urol (2005) 173:1557–61. doi:10.1097/01.ju.0000154610.81916.81
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7. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360(9327):103-106. doi:10.1016/s0140-6736(02)09408-4
8. Bolla M, de Reijke T, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. New Eng Jour of Med. 2009;360(24):2516–2027. doi: 10.1056/NEJMoa0810095.
9. Zapatero A, Gurerrero A, Maldonado X, et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localized prostate cancer (DART 01/05 GICOR): a randomised, controlled phase 3 trial. The Lancet Oncology. 16(3):320–327. doi: 10.1016/S1470-2045(15)70045-8. 3/15.
10. Cahill TP, Withey SJ, Hazell S, Cahill D, Kinsella N. Does bladder outflow obstruction obfuscate the traditional clinical factors that are used to assess the risk of prostate cancer at rapid-access diagnostic clinics? BJUI Compass. 2024;6(1):e478. Published 2024 Dec 20. doi:10.1002/bco2.478
11. Friedlander JI, Duty BD, Okeke Z, Smith AD. Obstructive uropathy from locally advanced and metastatic prostate cancer: an old problem with new therapies. J Endourol. 2012;26(2):102-109. doi:10.1089/end.2011.0227
12. Srivatsa N, Nagaraja H, Shweta S, Raghunath SK. Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature. Indian J Surg Oncol. 2017;8(2):175-180. doi:10.1007/s13193-016-0599-9
13. Calleris G, Filleron T, Kesch C, et al. Surgery with or Without Darolutamide in High-risk and/or Locally Advanced Prostate Cancer: The SUGAR (CCAFU-PR2) Phase 2 Trial Rationale and Protocol. Eur Urol Oncol. 2024;7(3):494-500. doi:10.1016/j.euo.2023.09.020
14. Bastian, P.J., et al. Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10. Cancer, 2006. 107: 1265. https://pubmed.ncbi.nlm.nih.gov/16900523
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16. EAU Guidelines. Edn. presented at the EAU Annual Congress Paris April 2024. ISBN 978-94-92671-23-3.
17. Lawton CAF, Lin X, Hanks GE, et al. Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017;98(2):296-303. doi:10.1016/j.ijrobp.2017.02.004
18. Parker CC, Kynaston H, Cook AD, et al. Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial. Lancet. 2024;403(10442):2416-2425. doi:10.1016/S0140-6736(24)00549-X
19. Meng MV, Grossfeld GD, Sadetsky N, Mehta SS, Lubeck DP, Carroll PR. Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Urology. 2002;60(3 Suppl 1):7-12. doi:10.1016/s0090-4295(02)01560-1
20. Gómez Rivas J, Ortega Polledo LE, De La Parra Sánchez I, et al. Current Status of Neoadjuvant Treatment Before Surgery in High-Risk Localized Prostate Cancer. Cancers (Basel). 2024;17(1):99. Published 2024 Dec 31. doi:10.3390/cancers17010099
21. Ashrafi A.N., Yip W., Aron M. Neoadjuvant Therapy in High-Risk Prostate Cancer. Indian J. Urol. 2020;36:251–261. doi: 10.4103/iju.IJU_115_20.
22. Kumar S., Shelley M., Harrison C., Coles B., Wilt T.J., Mason M.D. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst. Rev. 2006;2006:CD006019. doi:10.1002/14651858.CD006019.pub2.
23. Sankaran S, Govindaswamy TG, Dholakia K, Selvaraj N, Kanan D, Tiwari M, Ragavan N. Efficacy of Degarelix in the Neoadjuvant Setting in Managing Locally Advanced Prostate Cancer. Cureus. 2023 Jun 21;15(6):e40752. doi: 10.7759/cureus.40752. PMID: 37363117; PMCID: PMC10285566.
24. Bolla M, Henry A, Mason M, Wiegel T. The role of radiotherapy in localised and locally advanced prostate cancer. Asian J Urol. 2019;6(2):153-161. doi:10.1016/j.ajur.2019.02.001
25. Pinkawa M, Holy R, Piroth MD, et al. Consequential late effects after radiotherapy for prostate cancer - a prospective longitudinal quality of life study. Radiat Oncol. 2010;5:27. Published 2010 Apr 8. doi:10.1186/1748-717X-5-27
26. Bastos DA, Soares A, Schutz FAB, et al. Androgen Receptor Pathway Inhibitor Therapy for Advanced Prostate Cancer: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025;8(1):e2454253. Published 2025 Jan 2. doi:10.1001/jamanetworkopen.2024.54253
27. Rathkopf DE, Antonarakis ES, Shore ND, et al. Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone. Clin Cancer Res. 2017;23(14):3544-3551. doi:10.1158/1078-0432.CCR-16-2509
28. PROTEUS: A randomized, double-blind, placebo (PBO)-controlled, phase 3 trial of apalutamide (APA) plus androgen deprivation therapy (ADT) versus PBO plus ADT prior to radical prostatectomy (RP) in patients (pts) with localized or locally advanced high-risk prostate cancer (PC). Journal of Clinical Oncology Volume 40, Number 6_suppl. https://doi.org/10.1200/JCO.2022.40.6_suppl.TPS285
29. Clinton TN, Woldu SL, Raj GV. Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer. Expert Opin Pharmacother. 2017;18(8):825-832. doi:10.1080/14656566.2017.1328056
30. Sethi R, Sanfilippo N. Six-month depot formulation of leuprorelin acetate in the treatment of prostate cancer. Clin Interv Aging. 2009;4:259-267. doi:10.2147/cia.s4885
31. Veeratterapillay R, Goonewardene SS, Barclay J, Persad R, Bach C. Radical prostatectomy for locally advanced and metastatic prostate cancer. Ann R Coll Surg Engl. 2017;99(4):259-264. doi:10.1308/rcsann.2017.0031
32. Gandaglia G, Abdollah F, Hu J, et al. Is robot-assisted radical prostatectomy safe in men with high-risk prostate cancer? Assessment of perioperative outcomes, positive surgical margins, and use of additional cancer treatments. J Endourol. 2014;28(7):784-791. doi:10.1089/end.2013.0774
33. Sooriakumaran P, Karnes J, Stief C, et al. A Multi-institutional Analysis of Perioperative Outcomes in 106 Men Who Underwent Radical Prostatectomy for Distant Metastatic Prostate Cancer at Presentation. Eur Urol. 2016;69(5):788-794. doi:10.1016/j.eururo.2015.05.023
34. Raghavan D, Kannan D, Sekaran PG, et al. A Novel Technique of Renorrhaphy in Difficult Partial Nephrectomies by Single-Layered Parenchymal Imbrication. Cureus. 2023;15(7):e42702. Published 2023 Jul 30. doi:10.7759/cureus.42702
35. Kannan D, Sekaran PG, Panneerselvam A, Soni J, Jain N. Robotic transabdominal graft nephrectomy for renal mass in the transplant kidney. Videourology. 2023;37(1). https://doi.org/10.1089/vid.2023.0028
36. Tiwari M, Kannan D, Addla S, Ragavan M, Ragavan N. Robot-assisted repair of neobladder-vaginal fistula. Videourology. 2024. https://doi.org/10.1089/vid.2024.0055
37. Anast, J.W., Andriole, G.L. & Grubb, R.L. Managing the local complications of locally advanced prostate cancer. Curr prostate rep 6, 5–10 (2008). https://doi.org/10.1007/s11918-008-0002-6
38. Van Poppel H, Vekemans K, Da Pozzo L, et al. Radical prostatectomy for locally advanced prostate cancer: results of a feasibility study (EORTC 30001). Eur J Cancer. 2006;42(8):1062-1067. doi:10.1016/j.ejca.2005.11.030
2. Esperto F, Cacciatore L, Tedesco F, et al. Impact of Robotic Technologies on Prostate Cancer Patients' Choice for Radical Treatment. J Pers Med. 2023;13(5):794. Published 2023 May 5. doi:10.3390/jpm13050794
3. Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243-262. doi:10.1016/j.eururo.2020.09.042
4. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388
5. Meng MV, Elkin EP, Latini DM, Duchane J, Carroll PR. Treatment of Patients With High Risk Localized Prostate Cancer: Results From Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE). J Urol (2005) 173:1557–61. doi:10.1097/01.ju.0000154610.81916.81
6. Eastham J.A., Auffenberg G.B., Barocas D.A., Chou R., Crispino T., Davis J.W., Eggener S., Horwitz E.M., Kane C.J., Kirkby E., et al. Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, Part I: Introduction, Risk Assessment, Staging, and Risk-Based Management. J. Urol. 2022;208:10–18. doi: 10.1097/JU.0000000000002757.
7. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360(9327):103-106. doi:10.1016/s0140-6736(02)09408-4
8. Bolla M, de Reijke T, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. New Eng Jour of Med. 2009;360(24):2516–2027. doi: 10.1056/NEJMoa0810095.
9. Zapatero A, Gurerrero A, Maldonado X, et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localized prostate cancer (DART 01/05 GICOR): a randomised, controlled phase 3 trial. The Lancet Oncology. 16(3):320–327. doi: 10.1016/S1470-2045(15)70045-8. 3/15.
10. Cahill TP, Withey SJ, Hazell S, Cahill D, Kinsella N. Does bladder outflow obstruction obfuscate the traditional clinical factors that are used to assess the risk of prostate cancer at rapid-access diagnostic clinics? BJUI Compass. 2024;6(1):e478. Published 2024 Dec 20. doi:10.1002/bco2.478
11. Friedlander JI, Duty BD, Okeke Z, Smith AD. Obstructive uropathy from locally advanced and metastatic prostate cancer: an old problem with new therapies. J Endourol. 2012;26(2):102-109. doi:10.1089/end.2011.0227
12. Srivatsa N, Nagaraja H, Shweta S, Raghunath SK. Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature. Indian J Surg Oncol. 2017;8(2):175-180. doi:10.1007/s13193-016-0599-9
13. Calleris G, Filleron T, Kesch C, et al. Surgery with or Without Darolutamide in High-risk and/or Locally Advanced Prostate Cancer: The SUGAR (CCAFU-PR2) Phase 2 Trial Rationale and Protocol. Eur Urol Oncol. 2024;7(3):494-500. doi:10.1016/j.euo.2023.09.020
14. Bastian, P.J., et al. Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10. Cancer, 2006. 107: 1265. https://pubmed.ncbi.nlm.nih.gov/16900523
15. Yossepowitch, O., et al. Radical prostatectomy for clinically localized, high risk prostate cancer: critical analysis of risk assessment methods. J Urol, 2007. 178: 493. https://pubmed.ncbi.nlm.nih.gov/17561152
16. EAU Guidelines. Edn. presented at the EAU Annual Congress Paris April 2024. ISBN 978-94-92671-23-3.
17. Lawton CAF, Lin X, Hanks GE, et al. Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017;98(2):296-303. doi:10.1016/j.ijrobp.2017.02.004
18. Parker CC, Kynaston H, Cook AD, et al. Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial. Lancet. 2024;403(10442):2416-2425. doi:10.1016/S0140-6736(24)00549-X
19. Meng MV, Grossfeld GD, Sadetsky N, Mehta SS, Lubeck DP, Carroll PR. Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Urology. 2002;60(3 Suppl 1):7-12. doi:10.1016/s0090-4295(02)01560-1
20. Gómez Rivas J, Ortega Polledo LE, De La Parra Sánchez I, et al. Current Status of Neoadjuvant Treatment Before Surgery in High-Risk Localized Prostate Cancer. Cancers (Basel). 2024;17(1):99. Published 2024 Dec 31. doi:10.3390/cancers17010099
21. Ashrafi A.N., Yip W., Aron M. Neoadjuvant Therapy in High-Risk Prostate Cancer. Indian J. Urol. 2020;36:251–261. doi: 10.4103/iju.IJU_115_20.
22. Kumar S., Shelley M., Harrison C., Coles B., Wilt T.J., Mason M.D. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst. Rev. 2006;2006:CD006019. doi:10.1002/14651858.CD006019.pub2.
23. Sankaran S, Govindaswamy TG, Dholakia K, Selvaraj N, Kanan D, Tiwari M, Ragavan N. Efficacy of Degarelix in the Neoadjuvant Setting in Managing Locally Advanced Prostate Cancer. Cureus. 2023 Jun 21;15(6):e40752. doi: 10.7759/cureus.40752. PMID: 37363117; PMCID: PMC10285566.
24. Bolla M, Henry A, Mason M, Wiegel T. The role of radiotherapy in localised and locally advanced prostate cancer. Asian J Urol. 2019;6(2):153-161. doi:10.1016/j.ajur.2019.02.001
25. Pinkawa M, Holy R, Piroth MD, et al. Consequential late effects after radiotherapy for prostate cancer - a prospective longitudinal quality of life study. Radiat Oncol. 2010;5:27. Published 2010 Apr 8. doi:10.1186/1748-717X-5-27
26. Bastos DA, Soares A, Schutz FAB, et al. Androgen Receptor Pathway Inhibitor Therapy for Advanced Prostate Cancer: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025;8(1):e2454253. Published 2025 Jan 2. doi:10.1001/jamanetworkopen.2024.54253
27. Rathkopf DE, Antonarakis ES, Shore ND, et al. Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone. Clin Cancer Res. 2017;23(14):3544-3551. doi:10.1158/1078-0432.CCR-16-2509
28. PROTEUS: A randomized, double-blind, placebo (PBO)-controlled, phase 3 trial of apalutamide (APA) plus androgen deprivation therapy (ADT) versus PBO plus ADT prior to radical prostatectomy (RP) in patients (pts) with localized or locally advanced high-risk prostate cancer (PC). Journal of Clinical Oncology Volume 40, Number 6_suppl. https://doi.org/10.1200/JCO.2022.40.6_suppl.TPS285
29. Clinton TN, Woldu SL, Raj GV. Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer. Expert Opin Pharmacother. 2017;18(8):825-832. doi:10.1080/14656566.2017.1328056
30. Sethi R, Sanfilippo N. Six-month depot formulation of leuprorelin acetate in the treatment of prostate cancer. Clin Interv Aging. 2009;4:259-267. doi:10.2147/cia.s4885
31. Veeratterapillay R, Goonewardene SS, Barclay J, Persad R, Bach C. Radical prostatectomy for locally advanced and metastatic prostate cancer. Ann R Coll Surg Engl. 2017;99(4):259-264. doi:10.1308/rcsann.2017.0031
32. Gandaglia G, Abdollah F, Hu J, et al. Is robot-assisted radical prostatectomy safe in men with high-risk prostate cancer? Assessment of perioperative outcomes, positive surgical margins, and use of additional cancer treatments. J Endourol. 2014;28(7):784-791. doi:10.1089/end.2013.0774
33. Sooriakumaran P, Karnes J, Stief C, et al. A Multi-institutional Analysis of Perioperative Outcomes in 106 Men Who Underwent Radical Prostatectomy for Distant Metastatic Prostate Cancer at Presentation. Eur Urol. 2016;69(5):788-794. doi:10.1016/j.eururo.2015.05.023
34. Raghavan D, Kannan D, Sekaran PG, et al. A Novel Technique of Renorrhaphy in Difficult Partial Nephrectomies by Single-Layered Parenchymal Imbrication. Cureus. 2023;15(7):e42702. Published 2023 Jul 30. doi:10.7759/cureus.42702
35. Kannan D, Sekaran PG, Panneerselvam A, Soni J, Jain N. Robotic transabdominal graft nephrectomy for renal mass in the transplant kidney. Videourology. 2023;37(1). https://doi.org/10.1089/vid.2023.0028
36. Tiwari M, Kannan D, Addla S, Ragavan M, Ragavan N. Robot-assisted repair of neobladder-vaginal fistula. Videourology. 2024. https://doi.org/10.1089/vid.2024.0055
37. Anast, J.W., Andriole, G.L. & Grubb, R.L. Managing the local complications of locally advanced prostate cancer. Curr prostate rep 6, 5–10 (2008). https://doi.org/10.1007/s11918-008-0002-6
38. Van Poppel H, Vekemans K, Da Pozzo L, et al. Radical prostatectomy for locally advanced prostate cancer: results of a feasibility study (EORTC 30001). Eur J Cancer. 2006;42(8):1062-1067. doi:10.1016/j.ejca.2005.11.030