Oncological results of neoadjuvant chemohormonal therapy in patients with high and very high-risk prostate cancer
https://doi.org/10.17650/1726-9776-2020-16-1-54-63
Abstract
Tolsotogo St., Saint Petersburg 197022, Russia
Background. Prostate cancer (PCa) of a high and very high risk is a potentially fatal disease that requires an active multimodal approach, including the use of neoadjuvant drug treatment. As option for this treatment is neoadjuvant chemohormonal therapy (NCHT) followed by radical prostatectomy (RPE). However, data on the oncological results of treatment of such patients are still limited and the role of neoadjuvant therapy in the treatment of high and very high-risk PCa remains not fully understood.
Objective: to assess the oncological results of treatment patients with localized and locally advanced PCa of high and very high risk after NCHT.
Materials and methods. This was a prospective randomized study: patients with PCa of high and very high-risk groups (prostate specific antigen levels (PSA) >20 ng/ml and/or Gleason score ³8 and/or clinical stage >T2c) were treated with RPE only (group RPE; n = 35) or NCHT followed by RPE (NCHT/RPE group; n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6 subcutaneous injections every 28 days). After a follow-up examination evaluating the result of the neoadjuvant regimen, patients underwent RPE with extanded lymphadenectomy.
Results. A mean follow-up was 37.08 ± 20.46 months. A statistically significant reduction of prostate specific antigen >50 % post-chemohormonal therapy was observed in all 36 cases. Lower postoperative stage was noticed in 38.5 % in NCHT/RPE group compared with 2.7 % in RPE group. Similarly, positive surgical margin rate was higher in group without neoadjuvant therapy – 40 and 25 % (RPE group). Cancerspecific survival was 97.2 % in NCHT/RPE group and 87.56 % in the RP group (p = 0.037), cancer specific survival rate – 91.4 % and 97.2 % respectively (log-rank test p = 0.22). At the same time, no statistically significant differences were obtained in 3-year recurrence free survival between groups: 38.8 % in NCHT/RPE group versus 43.6 % in the RPE group (log-rank test p = 0.36).
Conclusion. Conducting NCHT before RPE is a safe and effective strategy in patients with PCa of high and very high risk groups and could improve oncological results.
About the Authors
M. V. BerkutRussian Federation
Department of Oncourology and General Oncology
68 Leningradskaya St., Pesochniji, Saint Petersburg 197758
A. S. Artemjeva
Department of Pathomorphology
68 Leningradskaya St., Pesochniji, Saint Petersburg 197758
Competing Interests:
Анна Сергеевна Артемьева, заведующая патологоанатомическим отделением с прозектурой, руководитель научной лаборатории морфологии опухолей, к.м.н., врач-патологоанатом
S. A. Reva
Department of Oncourology and General Oncology, N.N. Petrov National Medical Research Center of Oncology; Urooncological Department, Pavlov First Medical State University
68 Leningradskaya St., Pesochniji, Saint Petersburg 197758;
17–54 L’va Tolsotogo St., Saint Petersburg 197022
S. S. Tolmachev
Department of Pathomorphology
68 Leningradskaya St., Pesochniji, Saint Petersburg 197758
Competing Interests:
Станислав Сергеевич Толмачев, патологоанатомическое отделение с прозектурой, научная лаборатория морфологии опухолей, врач-патоморфолог
S. B. Petrov
Department of Oncourology and General Oncology, N.N. Petrov National Medical Research Center of Oncology; Urooncological Department, Pavlov First Medical State University
68 Leningradskaya St., Pesochniji, Saint Petersburg 197758;
17–54 L’va Tolsotogo St., Saint Petersburg 197022
A. K. Nosov
Russian Federation
Department of Oncourology and General Oncology
68 Leningradskaya St., Pesochniji, Saint Petersburg 197758
References
1. Siegel R., Naishadham D., Jemal A. Cancer statistics. CA Cancer J Clin 2013;63(1):11–30. DOI: 10.3322/caac.21166.
2. Cooperberg M.R., Cowan J., Broering J.M., Carroll P.R. High-risk prostate cancer in the United States, 1990–2007. World J Urol 2008;26(3):211–8. DOI: 10.1007/s00345-008-0250-7.
3. D’Amico A.V., Moul J., Carroll P.R. et al. Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. J Clin Oncol 2003;21:2163–72. DOI: 10.1200/JCO.2003.01.075.
4. Zelefsky M.J., Eastham J.A., Cronin A.M. et al. Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: a comparison of clinical cohorts adjusted for case mix. J Clin Oncol 2010;28(9):1508–13. DOI: 10.1200/JCO.2009.22.2265.
5. Cooperberg M.R., Vickers A.J., Broering J.M., Carroll P.R. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgendeprivation therapy for localized prostate cancer. Cancer 2010;116:5226–34. DOI: 10.1002/cncr.25456.
6. Joniau S., Tosco L., Briganti A. et al. Results of surgery for high-risk prostate cancer. Curr Opin Urol 2013;23(4):342–8. DOI: 10.1097/MOU.0b013e3283620f60.
7. Mohler J.L., Armstrong A.J., Bahnson R.R. et al. Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2012;10(9):1081–7. DOI: 10.6004/jnccn.2012.0114.
8. Goldberg H., Baniel J., Yossepowitch O. Defining high-grade prostate cancer. Curr Opin Urol 2013;23(4):337–41. DOI: 10.1097/MOU.0b013e328361dba6.
9. Shelley M.D., Kumar S., Wit T. et al. A systematic review and meta-analysis of randomized trials of neo-adjuvant hormone therapy for localised and locally advanced prostate carcinoma. Cancer Treat Rev 2009;35(1):9–17. DOI: 10.1016/j.ctrv.2008.08.002.
10. Nosov A.K., Petrov S.B., Reva S.A. et al. Results of a unicenter randomized study of the safety and efficiency of docetaxel chemotherapy before radical prostatectomy in patients with intermediateand high-risk prostate cancer: an 11.4-year follow-up. Onkourologiya = Cancer Urology 2014;(4):52–61. (In Russ.).
11. Nosov A.K., Reva S.A., Berkut M.V. et al. Neoadjuvant for patients with high and very high risk prostate cancer. Voprosy onkologii = Problems in Oncology 2019;65(5):726–35. (In Russ.).
12. Blute M.L., Bergstralh E.J., Iocca A. et al. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol 2001;165(1):119–25. DOI: 10.1097/00005392-200101000-00030.
13. Reese A.C., Pierorazio P.M., Han M., Partin A.W. Contemporary evaluation of the National Comprehensive Cancer Network prostate cancer risk classification system. Urology 2012;80(5):1075–9. DOI: 10.1016/j.urology.2012.07.040.
14. Epstein J.I., Egevad L., Amin M.B. et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 2016; 40(2):244–52. DOI: 10.1097/PAS.0000000000000530.
15. Picus J., Schultz M. Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results. Semin Oncol 1999;26(suppl 17):14–8.
16. Oh W.K., George D.G., Kaufman D.S. et al. Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: a preliminary report. Semin Oncol 2001;28(4):40–4. DOI: 10.1016/s0093-7754(01)90153-8.
17. Dreicer R., Magi-Galluzzi C., Zhou M. et al. Phase II of neoadjuvant docataxel before radical prostatectomy for locally advanced prostate cancer. Urology 2004;63(6):1138–42.
18. Febbo P.G., Richie J.P., George D.J. et al. Neoadjuvant docataxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res 2005;11(15):5233–40. DOI: 10.1158/1078-0432.CCR-05-0299.
19. Thalgott M., Horn T., Neck M.M. et al. Long-term results of a phase II study with neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high-risk prostate cancer. J Hematol Oncol 2014;7:20. DOI: 10.1186/1756-8722-7-20.
20. Nosov A., Reva S., Petrov S. et al. Neoadjuvant chemotherapy using reduceddose docetaxel followed by radical prostatectomy for patients with intermediate and high-risk prostate cancer: a single-center study. Prostate 2016;76(15):1345–52. DOI: 10.1002/pros.23165.
21. 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. DOI: 10.1038/sj.bjc.6605320.
22. Chi K.N., Chin J.L., Winquist E. et al. Multicenter phase II study of combined neoadjuvant docetaxel and hormone therapy before radical prostatectomy for patients with high risk localized prostate cancer. J Urol 2008;180(2):565–70. DOI: 10.1016/j.juro.2008.04.012.
23. Ustinova T.V., Nyushko K.M., Bolotina L.V. et al. Neoadjuvant and adjuvant chemohormonal therapy in patients with high-risk and very highrisk prostate cancer: our experience. Onkourologiya = Cancer Urology 2018;14(3):58–67. (In Russ.) DOI: 10.17650/1726-9776-2018-14-3-58–67.
24. Magi-Galluzzi C., Zhou M., Reuther A.M. et al. Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study. Cancer 2007;110(6):1248–54. DOI: 10.1002/cncr.22897.
25. Herkommer K., Kuefer R., Gschwend J.E. et al. Pathological T0 prostate cancer without neoadjuvant therapy: clinical presentation and follow-up. Eur Urol 2004;45(6):36–41. DOI: 10.1016/j.eururo.2003.08.001.
26. Prayer-Galetti T., Sacco E., Pagano F. et al. Long-term follow-up of a neoadjuvant chemohormonal taxane-based phase II trial before radical prostatectomy in patients with non-metastatic high-risk prostate cancer. BJU Int 2007;100(2):274–80 DOI: 10.1111/j.1464-410X.2007.06760.x.
27. Narita S., Tsuchiya N., Kumazawa T. et al. Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer. World J Surg. Oncol 2012;10:1. DOI: 10.1186/1477-7819-10-1.
28. Sella A., Zisman A., Kovel S. et al. Neoadjuvant chemohormonal therapy in poor-prognosis localized prostate cancer. Urology 2008;71(2):323–7. DOI: 10.1016/j.urology.2007.08.060.
29. Civantos F., Marcial M.A., Banks E.R. et al. Pathology of androgen deprivation therapy in prostate carcinoma. A comparative study of 173 patients. Cancer 1995;75(7):1634–41. DOI: 10.1002/1097-0142(19950401)75: 7<1634::aid-cncr2820750713>3.0.co;2-#.
30. Bullock M.J., Srigley J.R., Klotz L.H. et al. Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma: a detailed analysis of radical prostatectomy specimens from a randomized trial. Am J Surg Pathol 2002;26(11):1400–13. DOI: 10.1097/00000478-20021100000002.
Review
For citations:
Berkut M.V., Artemjeva A.S., Reva S.A., Tolmachev S.S., Petrov S.B., Nosov A.K. Oncological results of neoadjuvant chemohormonal therapy in patients with high and very high-risk prostate cancer. Cancer Urology. 2020;16(1):54-63. (In Russ.) https://doi.org/10.17650/1726-9776-2020-16-1-54-63