The clinical research program of the Claire and John Bertucci Center for Genitourinary Cancers is a multidisciplinary effort to understand cancer biology, discover novel agents, and improve treatment outcomes for patients with genitourinary malignancies including cancers of the prostate, bladder, and kidney. 

Improve outcomes for men with early stage prostate cancer

• To compare the cancer control and quality of life outcomes of laparoscopic and open prostatectomy for men with early stage prostate cancer
• Complete our long-term evaluations of cancer control of the first randomized controlled trial of dose escalation with proton beam radiation therapy for patients with early prostate cancer
• Complete the first reported quality of life evaluations of men undergoing proton beam radiation for early stage prostate cancer
• Develop the targeted pelvic lymph nodal radiation using intensity modulated radiation therapy (IMRT) in men with locally advanced prostate cancer
• Compare the cancer control and quality of life outcomes of two conformal radiation therapy treatment schedules using image guided radiation therapy
• Assess the impact of obesity and diabetes on outcomes following prostate cancer treatment
• Evaluate novel methods for detection of lymph node metastases in men with prostate cancer
• Evaluate novel biomarkers and genetic profiles to predict cancer outcomes and guide treatment

Develop novel therapies for recurrent and metastatic disease

• Evaluate whether adjuvant chemotherapy improves survival in men after with locally-advanced prostate cancer
• Evaluate whether denosumab, a novel osteoclast-targeted therapy, prevents bone metastases in men with high-risk androgen-independent prostate cancer
• Evaluate the efficacy and predictors of response of sunitinib, a multitargeted kinase inhibitor, in men with androgen-independent prostate cancer
• Evaluate the efficacy and predictors of response for yondelis, a novel marine-derived pharmaceutical, in men with chemotherapy-refractory metastatic prostate cancer

Improve the quality of life for prostate cancer survivors

• Compare the effects of different forms of treatment on patient-reported quality of life in men with early stage prostate cancer
• To compare quality of life outcomes with proton beam radiation therapy to IMRT for men with early stage prostate cancer
• Evaluate strategies to prevent osteoporosis and fractures in men receiving long-term hormone therapy
• Assess the metabolic complications of hormone therapy
• Evaluate the efficacy of intensive lifestyle intervention of risk of diabetes and cardiovascular disease in men receiving long-term hormone therapy

Bladder Cancer
Transitional cell carcinoma of the urinary bladder is a leading cause of cancer death. In the United States, more than 67,000 men and women are diagnosed with bladder cancer annually and approximately 13,750 die from the disease. The spectrum of transitional cell carcinoma includes superficial, invasive, and metastatic disease, each with its own clinical presentation, prognosis, and treatment. The goals of the Center’s clinical research program in bladder cancer are to develop innovative strategies to treat invasive bladder cancer and to evaluate biologic predictors of cancer outcomes.

• Continue to lead NCI cooperative group evaluations of selective bladder preservation for patients with invasive bladder cancer using transurethral surgery, radiation therapy, and novel chemotherapy agents
• Compare the efficacy of two different two-drug radiosensitizing regimens in patients with undergoing selective bladder preservation by trimodality therapy for muscle-invasive disease.
• Evaluate the efficacy of trastuzumab for patients with bladder tumors that overexpress HER-2
• Evaluate the efficacy and safety of selective bladder preservation using transurethral surgery, radiation therapy, and chemotherapy for patients with refractory high-grade T1 bladder tumors

• Evaluate the role of novel biomarkers and tumor gene profiles to optimize treatment approaches
• Assess whether over-expression of vascular endothelial growth factor and its receptor are associated with poor response to combined modality therapy

Optimize the treatment for early stage renal cell carcinoma

• Evaluate the efficacy and safety of radiofrequency ablation as a minimally invasive alternative to surgery for patients with early stage renal cell carcinoma
• Identify novel biomarkers associated with recurrence after treatment for early stage disease 

Develop novel therapeutic approaches to treat advanced stage renal cell carcinoma 

• Assess the optimal timing and sequence of anti-angiogenic therapy for patients with metastatic renal cell carcinoma
• Evaluate the efficacy and safety of combinations of anti-angiogenic agents in patients with metastatic renal cell carcinoma
• Assess new strategies to treat patients when they develop resistance to anti-angiogenic therapy
• Determine whether novel biomarkers and/or tumor characteristics predict response to specific targeted therapies

Selected Clinical Research Protocols

• An Open-Label, Phase II Study to Evaluate the Efficacy and Tolerability of ABT-869 in Subjects With Advanced Renal Cell Carcinoma (RCC) Who Have Previously Received Treatment With Sunitinib

• A Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab with Daily Irradiation of Paclitaxel Alone with Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates with Muscle-Invasive Bladder Cancer

• Phase II study of Yondelis in men with advanced prostate carcinoma

• A Phase II Randomized Trial for Patients with Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy

• A Phase I Open Label Dose Escalation Study of the 17ahydroxylase/C17,20- lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer

• RTOG 0518 A Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Zometa for the Prevention of Osteoporosis and Associated Fractures in Patients Receiving Radiation Therapy and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer

• A Randomized, Double-Blind, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of AMG 745 in Men With Prostate Cancer Receiving Androgen Deprivation Therapy

• RTOG 0521: A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs AS and 3DCRT/IMRT Followed by Chemotherapy with Docetaxel and Prednisone for Localized, High-Risk Prostate Cancer

• A Randomized, Double-Blind, Multicenter Study of Denosumab Compared with Zoledronic Acid (Zometa) in the Treatment of Bone Metastases in Men with Hormone-Refractory Prostate Cancer

Faculty
Donald S. Kaufman, MD
Clinical Director
Matthew R. Smith, MD, PhD
Director
W. Scott McDougal, MD
Chief, Department of Urology
William U. Shipley, MD
Vice Chair for Clinical Research, Department of Radiation Oncology

John J. Coen, MD
Douglas M. Dahl, MD
Mukesh Harisinghani, MD
Niall Heney M., MB, MD
Michael A. Hurwitz, MD
Othon Iliopoulos, MD
Richard Lee, MD, PhD
Francis J. McGovern, MD
M. Dror Michaelson, MD, PhD
Aria F. Olumi, MD
Shahin Tabatabaei, MD
James A. Talcott, MD
Chin-Lee Wu, MD, PhD
Robert H. Young, MD
Anthony L. Zietman, MD

Selected Publications
Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA, Shipley WU. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 2005; 294(10): 1274-6.

Shih H, Harisinghani M, Zietman A, Wolfgang J, Saksena M, Weissleder R. Mapping of nodal disease in locally advanced prostate cancer: rethinking the clinical target volume for pelvic nodal radiation based on vascular rather than bony anatomy.  Int J Radiat Oncol Biol Phys 2005; 63: 1262-1269.

Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006; 295(21):2516-24.

Clark JA, Talcott JA. Confidence and uncertainty long after initial treatment for early prostate cancer: survivors’ views of cancer control and the treatment decisions they made. J Clin Oncol 2006; 24:4457-63.

Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 2006; 91(4):1305-8.

Shipley WU, DeSilvio M, Pilepich MV, Roach M III, Walkov HB, Sause WT, Rubin P,and Lawton CA,  Early initiation of salvage hormone therapy influences survival in patients who failed initial radiation for locally advanced prostate cancer: A secondary analysis of RTOG Protocol 86-10.  Int J Radiat Oncol Biol Phys 2006; 64:1162-1167.

Keating NL, O’Malley JO, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006, 24(27): 4448-4456.

Dahl DM, He W, Lazarus R, McDougal WS, Wu CL. Pathologic outcome of laparoscopic and open radical prostatectomy. Urology 2006; 68(6):1253-6.

Jiang Z, Chu PG, Woda BA, Rock KL, Liu Q, Hsieh CC, Li C, Chen W, Duan HO, McDougal S, Wu CL. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol 2006; 7(7): 556-564.

Michaelson MD, Kaufman DS, Lee H, McGovern FJ, Kantoff PW, Fallon MA, Finkelstein JS, Smith MR. Randomized controlled trial of annual zolendronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol 2007; 25(9):1038-42.

Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR. Obesity and prostate cancer-specific mortality following radiation therapy and androgen suppression for locally advanced prostate cancer: an analysis of RTOG 85-31. Cancer 2007; (in press).