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Neoadjuvant Chemotherapy Followed by Radical Prostatectomy in Patients with Intermediate to High Risk Prostate Cancer
Mehrdad Alemozaffar, M.D. 1, Stephen B. Williams, M.D. 1, Xiangmei Gu, Ph.D. 2, Nathanael Hevelone, 2, Stuart R. Lipsitz, Ph.D.2, William K. Oh, M.D. 3, Tiffany Lin, B.S. 3, Aaron C. Weinberg, M.D. 1, Peter Chang, M.D. 1, Toni K. Choueiri, M.D. 4, Glenn Bubley, M.D. 4, WIlliam DeWolf, M.D.4, Jerome P. Richie, M.D. 1, Jim C.Hu, M.D., M.P.H. 1.
1Division of Urologic Surgery, Brigham and Women's Hospital, Boston, MA, USA, 2Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA,USA, 3Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 4Cancer Center, Beth Isreal Deaconess Medical Center

Introduction
Patients with higher risk prostate cancer based on D’Amico criteria experience worse rates of biochemical recurrence-free survival following radical prostatectomy (RP). Various treatment methods have been employed prior to RP to improve survival including neoadjuvant hormone or neoadjuvant chemotherapy; however, the role of NCRP and patient selection remains largely unknown. We review our experience with NCRP and compare outcomes to controls with intermediate and high-risk prostate cancer undergoing RP alone.
Methods
From 7/2000 to 5/2006, 82 men with intermediate and high-risk disease received neoadjuvant chemotherapy with different combinations of docetaxel, bevacizumab, imatinib, or estramustine then underwent open RP at the Brigham and Women’s Hospital or Beth Israel Deaconess Medical Center as part of clinical protocols. Pathologic, perioperative and short-term cancer control outcomes were compared to 59 men with intermediate and high-risk disease features undergoing RP alone during the same time frame by the same surgeons.
Results
Men undergoing NCRP vs. RP were less likely to receive nerve-sparing (47.5% vs. 89.8%, p<0.001), experienced longer operative times (254 vs. 187 min, p<0.001), and longer hospital stays (3.1 vs. 2.3 days, p=<0.001). Intraoperative blood loss was similar (625 vs. 750 mL, p=0.148); however, NCRP vs. RP was associated with more blood transfusions (86.6% vs. 6.8%, p=<0.001). There were 3 vs. 0 intraoperative complications for NCRP vs. RP including 2 rectal injuries and 1 ureteral injury, otherwise rates of other complications were similar and rare (<5% in either group). Additionally, NCRP vs. RP subjects were more likely to have ≥pT3 disease (56.2% vs. 23.7%, p<0.001) and positive surgical margins (36.6% vs. 15.3%, p=0.005). Finally, NCRP vs. RP subjects had a higher risk of PSA recurrence (35.7% vs. 8.3%, p=0.007) and greater subsequent use of additional radiation and/or hormonal therapy (46.3% vs. 12.0%, p<0.001).
Conclusion
NCRP vs. RP was associated with longer operative times, length of stay, and greater perioperative morbidity, it did not appear to improve surgical margin rates or short-term cancer control. These differences may be related to the worse baseline risk features in patients undergoing NCRP vs. RP. With the development of novel targeted prostate therapies in prostate cancer, NRCP remains a viable treatment paradigm albeit with potentially increased morbidity.

Comparison of Perioperative Outcomes of NCRP and RP
NCRP, n=82RP, n=59p-value
Nerve Sparing<0.001
None43 (52.4%)6 (10.2%)
Unilateral38 (46.3%)42 (71.2%)
Bilateral1 (1.2%)11 (18.6%)
Median Operative Time (min)254187< 0.001
Median EBL (mL)6257500.098
Any Blood Transfusions71 (86.6%)4 (6.8%)<0.001
Postoperative Blood Transfusions6 (7.3%)00.034
Mean Hospital Stay (days)3.12.30.002


Comparison of Operative Complications in NCRP and RP
NCRP, n=82RP, n=59p-value
Rectal Injury2 (2.5%)00.233
Ureteral Injury1 (1.2%)00.395
Urinary Retention4 (4.9%)2 (3.4%)0.666
Anastomotic Stricture4 (4.9%)3 (5.1%)0.956
Delayed Urine Leak1 (1.2%)00.395
Postoperative Hypotension3 (3.7%)1 (1.7%)0.488
Postoperative DVT/PE1 (1.2%)00.395
Pronlonged Hematuria02 (3.4%)0.093
Postoperative UTI02 (3.4%)0.093


Comparison of Positive Surgical Margins, Recurrence, Adjuvant therapy in NCRP and RP
NCRP, n=82RP, n=59p-value
Positive Surgical Margin30 (36.6%)9 (15.3%)0.005
Patients with undetectable PSA postoperatively70 (86.4%)48 (98%)0.030
Patients with Biochemical Recurrence25 (35.7%)4 (8.3%)0.0007
Recieved Any Adjuvant Therapy38 (46.3%)7 (12.0%)<0.001
Recieved Adjuvant XRT + ADT22 (26.8%)4 (6.8%)0.003
Recieved Adjuvant XRT7 (8.5%)1 (1.7%)0.083
Recieved Adjuvant ADT8 (9.8%)2 (3.4%)0.146
Recieved Adjuvant Chemotherapy6 (7.3%)00.034
Mean Nadir PSA0.681.530.451


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