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Radical Prostatectomy in the Treatment of High-Risk but Clinically Localized Prostate Cancer James A. Eastham, MD Memorial Sloan-Kettering Cancer Center.

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Presentation on theme: "Radical Prostatectomy in the Treatment of High-Risk but Clinically Localized Prostate Cancer James A. Eastham, MD Memorial Sloan-Kettering Cancer Center."— Presentation transcript:

1 Radical Prostatectomy in the Treatment of High-Risk but Clinically Localized Prostate Cancer James A. Eastham, MD Memorial Sloan-Kettering Cancer Center 353 East 68 th Street New York, NY 10021, USA NOTE: The following slides are to be used for medical education purposes only. Copyright belongs to Prous Science and Prous Science is not responsible for any modification or change made by the users to these slides.

2 Radical Prostatectomy in the Treatment of High-Risk but Clinically Localized Prostate Cancer INDEX Defining high-risk but clinically localized prostate cancer Outcomes after radical prostatectomy (RP) based on the definition used to define high-risk patients Efforts to improve outcomes in high-risk patients Key Words: prostate cancer, radical prostatectomy, risk assessment

3 Extent~Clinical/path stage (TNM) Grade~Gleason patterns (1-5) Volume~Serum PSA level Each is an independent predictor of risk, but when combined the predictive accuracy increases There are no standardized criteria to define high-risk prostate cancer Established Factors that Characterize Prostate Cancer Risk

4 Predicting Risk for Prostate Cancer At diagnosis –Partin tables –Risk groups –Pre-treatment nomograms After radical prostatectomy –Pathological features –Post-treatment nomograms

5 Radical Prostatectomy for Clinically Localized, High-Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods 1 Analyze outcomes for patients classified as high risk by various definitions that are in use in the medical literature, using adverse pathological features and BCR as endpoints

6 Study Cohort 5840 patients undergoing RP between 6/83-12/04 for clinical stage T1-T3 N0M0 adenocarcinoma of the prostate Excluded : 790 patients -neoadjuvant hormonal treatment 25 patients -neoadjuvant chemotherapy 31 patients -adjuvant radiation therapy 286 patients -missing data (stage, grade or PSA) Final study population:4708 patients with complete clinical, pathological and outcome data

7 CharacteristicNo. Patients (%) Median age at surgery, years (IQR)61 (56, 65) Median preoperative PSA, ng/ml (IQR)6.19 (4.40, 9.10) Median preoperative PSA velocity, ng/ml/y (IQR)*1.08 (-0.99, 3.58) Biopsy Gleason Sum (68) 7 (3+4)903 (19) 7 (4+3)337 (7) (6) 1992 TNM Clinical Stage T1AB110 (2) T1C2148 (46) T2A1048 (22) T2B823 (18) T2C435 (9) T3144 (3) Preoperative Patient Characteristics

8 High-Risk Definitions Based on Preoperative Variables 1) Biopsy Gleason Score (bGS) 8 Reference 2 2) Preoperative PSA 20 3) 1992 TNM stage T3 Reference 3 4) PSA 20 or cT2C or bGS 8 References 4, 5 5) 5-year PFP < 50% (nomogram) Reference 6 6) PSA 20 or cT3 or bGS 8 Reference 7 7) PSA 15 or cT2B or bGS 8 References 8, 9 8) PSA velocity > 2 ng/ml/y Reference 10

9 Number (%) of Patients in Study Population According to Definition of High Risk 1 1) Biopsy Gleason Score (bGS) 8274 (6%) 2) Preoperative PSA (6%) 3) 1992 TNM stage T3144 (3%) 4) PSA 20 or cT2C or bGS 8957 (20%) 5) 5-year PFP < 50% (nomogram)391 (8%) 6) PSA 20 or cT3 or bGS 8605 (13%) 7) PSA 15 or cT2B or bGS (37%) 8) PSA velocity > 2 ng/ml/y952 (38%)* * Percentage of the 2521 patients with calculable preoperative PSA velocity

10 High-Risk DefinitionNo. GS 8-10 n=321 ECE n=1331 1Biopsy Gleason Score (bGS) (52)163 (60) 2Preoperative PSA (16)168 (61) TNM cT (28)103 (71) 4PSA 20 or 1992 TNM cT2C or bGS (21)505 (53) 5Nomogram 5-year PFP 50% (27)266 (68) 6PSA 20 or 1992 TNM cT3 or bGS (30)362 (59) 7PSA 15 or 1992 TNM cT2B or bGS (14)797 (46) 8Preoperative PSA velocity > 2 ng/ml/y95296 (10)332 (35) Pathological Features Based on Definition of High-Risk Prostate Cancer

11 High-risk definition PSM n=951 SVI n=382 LNI n=182 OC n=3280 Biopsy Gleason Score (bGS) (30)69 (25)52 (19)96 (35) Preoperative PSA (46)91 (33)40 (15)90 (33) 1992 TNM cT338 (26)45 (31)33 (23)32 (22) PSA 20 or 1992 TNM cT2C or bGS (29)203 (21)111 (12)407 (43) Nomogram 5-year PFP 50%149 (38)117 (30)71 (18)109 (28) PSA 20 or 1992 TNM cT3 or bGS (34)166 (24)95 (16)205 (34) PSA 15 or 1992 TNM cT2B or bGS (27)281 (16)147 (8)892 (51) Preoperative PSA velocity > 2 ng/mL/y209 (22)94 (10)62 (7)598 (63) PSM: positive surgical margin; SVI: seminal vesicle invasion; LNI: lymph node invasion; OC: organ-confined

12 High-Risk Prostate Cancer: Progression-free Probability (PFP) by Definition

13 High-Risk Prostate Cancer: 5- and 10-year PFP High Risk Definition BCR / No. patients 5-year PFP* (95% CI) 10-year PFP* (95% CI) Biopsy Gleason / (46, 60)42 (38, 56) Preoperative PSA / (50, 62)47 (40, 54) 1992 TNM stage T362 / (39, 58) 41 (29, 53) PSA 20 or T2C or GS 8299 / (65, 71)59 (55, 63) Nomo 5-year PFP 50%180 / (47, 57)43 (36, 49) PSA 20 or T3 or GS 8234 / (53, 62)50 (44, 55) PSA 15 or T2B or GS 8466 / (71, 75)65 (62,68) PSA velocity > 2 ng/ml/y161 / (77, 83) 74 (70, 78)

14 High-Risk Prostate Cancer: 5- and 10-year PFP Depending on the definition of high-risk, the: –5-year PFP ranges from 49% to 80% –10-year PFP ranges from 41% to 74%

15 High-Risk Prostate Cancer – Hazard Ratios for Biochemical Recurrence (BCR) Compared to Non-High- Risk Patients High Risk DefinitionBCR / No. PatientsHR (95% CI) Biopsy Gleason Score / (3.5, 5.3) Preoperative PSA / (3.2, 4.7) 1992 TNM stage T362 / (3.4, 5.7) PSA 20 or T2C or bGS 8299 / (2.8, 3.8) Nomogram 5-year PFP 50%180 / (4.1, 5.7) PSA 20 or T3 or bGS 8234 / (3.7, 5.1) PSA 15 or T2B or bGS 8466 / (3.2, 4.4) PSA velocity > 2 ng/ml/y161 / (1.5, 2.3) All hazards ratios significant at the level

16 High-Risk Prostate Cancer – Hazard Ratios for Biochemical Recurrence (BCR) Compared to Non- High-Risk Patients All high-risk definitions select men more likely to experience BCR than non-high-risk patients However, depending on the definition, the risk of BCR ranges from 1.8 to 4.8 times

17 High-Risk Prostate Cancer: Cancer-Specific Survival

18 High-Risk Prostate Cancer: Estimated 12-Year Disease- Specific Survival (DSS) after RP High Risk Definition12-year DSS (95% CI) Biopsy Gleason (69, 91) Preoperative PSA 2086 (76, 96) 1992 TNM stage T378 (69, 89) PSA 20 or T2C or GS 893 (89, 97) Nomogram 5-year PFP 50%90 (84, 96) PSA 20 or T3 or GS 891 (86, 96) PSA 15 or T2B or GS 894 (92, 96) PSA velocity > 2 ng/ml/y94 (90, 98)

19 High-Risk Prostate Cancer – Cancer-Specific Survival Regardless of the definition of high-risk prostate cancer, men treated with radical prostatectomy have an excellent cancer-specific survival at 10 to 15 years after surgery

20 Identifying and Treating Men with High-Risk but Clinically Localized Prostate Cancer Predictive tools have been developed to identify the risk that a patient will fail definitive local therapy (either surgery or radiation) –The risk will depend on the definition used While radical prostatectomy or radiation can cure some men with high- risk disease, local therapy alone is often inadequate for patients with high-risk prostate cancer Based on this assessment, patients can be identified to participate in trials examining multimodal therapy for clinically localized but high-risk prostate cancer

21 Multimodal Treatment is the Standard of Care for Many Cancers Testis Bladder Breast Colon Lung Surgery + Radiation + Chemotherapy + Hormonal Therapy This strategy requires effective local and systemic therapy

22 Multimodal Treatment in Prostate Cancer Local treatment effectively eradicates local disease Radiation plus hormonal therapy has been demonstrated to improve survival in men with high-risk prostate cancer compared to radiation alone, but many men still experience cancer recurrence 11 Survival outcomes after radical prostatectomy have not been improved with hormonal therapy except in men with node- positive disease 12 More effective systemic therapy is needed in prostate cancer

23 A Reason For Optimism? Two randomized, phase III trials have demonstrated a survival advantage of approximately 20% in men with hormone-refractory prostate cancer treated with docetaxel chemotherapy 13, 14

24 Implications of these Studies The 20% improvement in survival is similar to other studies in metastatic solid tumors (breast, colon) that have shown a survival benefit when moving therapy earlier Because of the results from these studies, neoadjuvant and adjuvant trials using docetaxel in high-risk prostate cancer have been opened –Should result in a new treatment paradigm for high-risk, but localized prostate cancer

25 Conclusions Patients diagnosed with high-risk cancers do not uniformly have poor prognosis after RP but can be selected based on the features of their cancer Overall risk of locally advanced or occult metastatic disease and incidence of PSA relapse may vary greatly depending on the definition used Experience in other cancers demonstrates that multimodal strategies improve patient outcomes Support Clinical Trials!

26 References 1. Yossepowitch, O., Eggener, S.E., Bianco, F.J., Jr., Carver, B.S., Serio, A., Scardino, P.T., Eastham, J.A. Radical prostatectomy for clinically localized, high risk prostate cancer: Critical analysis of risk assessment methods. J Urol 2007, 69(6): Donohue, J.F., Bianco, F.J., Jr, Kuroiwa, K., Vickers, A.J., Wheeler, T.M., Scardino, P.T., Reuter, V.A., Eastham, J.A. Poorly differentiated prostate cancer treated with radical prostatectomy: long-term outcome and incidence of pathological downgrading. J Urol 2006, 176: Ward, J.F., Slezak, J.M., Blute, M.L., Bergstralh, E.J., Zincke, H. Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15- year outcome. BJU Int 2005, 95:

27 References 4.D'Amico, A.V., Whittington, R., Malkowicz, S.B. et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998, 280: Grossfeld, G.D., Chang, J.J., Broering, J.M., Li, Y.P., Lubeck, D.P., Flanders, S.C., Carroll, P.R. Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor database. J Urol 2001, 165: Kattan, M.W., Eastham, J.A., Stapleton, A.M., T.M. Wheeler, T.M., Scardino, P.T. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 1998, 90:

28 References 7. Scardino, P. Update: NCCN prostate cancer Clinical Practice Guidelines. J Natl Compr Canc Netw 2005, 3 (Suppl): S Clark, P.E., Peereboom, D.M., Dreicer, R., Levin, H.S., Clark, S.B., Klein, E.A. Phase II trial of neoadjuvant estramustine and etoposide plus radical prostatectomy for locally advanced prostate cancer. Urology 2001, 57: Dreicer, R., Magi-Galluzzi, C., Zhou, M., Rothaermel, J., Reuther, A., Ulchaker, J., Zippe, C., Fergany, A., Klein, E.A. Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer. Urology 2004, 63: D'Amico, A.V., Chen, M.H., Roehl, K.A., Catalona, W.J. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004, 351:

29 References 11. Bulla, 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): Messing, E., Manola, J., Yao, J., Kiernan, M., Crawford, D., Wilding, G., di'SantAgnese, P., Trump, D. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006, 7(6): Petrylak, D.P., Tangen, C.M., Hussain, M.H. et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004, 351:1513– Tannock, I.F., de Wit, R., Berry, W.R. et al.; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004, 351:1502–12.


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