Massachusetts General Hospital | Cancer Center

Genitourinary Cancers Investigators Donald S. Kaufman, MD
Mathew R. Smith, MD, PhD
William U. Shipley, MD
W. Scott McDougal, MD
John J. Coen, MD
Douglas M. Dahl, MD
Adam Scott Feldman, MD, MPH
Mukesh G. Harisinghani, MD
Niall M. Heney, MB, MD
Michael E. Hurwitz, MD, PhD
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

Research Summary

Prostate Cancer

Prostate cancer is the most common noncutaneous malignancy and a leading cause of cancer death in men worldwide. In the United States, more than 220,000 men are diagnosed with prostate cancer annually and approximately 27,000 die from advanced disease. The goals of the Centers clinical research program in prostate cancer are to improve outcomes for men with early stage prostate cancer, develop novel therapies for recurrent and metastatic disease, and improve the quality of life for prostate cancer survivors.

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
• 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 Centers' clinical research program in bladder cancer are to develop innovative strategies to treat invasive bladder cancer and to evaluate biologic predictors of cancer outcomes.

Develop innovative strategies to treat invasive bladder cancer:

• 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 biological predictors of cancer outcomes
• 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

Kidney Cancer

Renal cell carcinoma or kidney cancer is a devastating malignancy that is responsible for more than 13,000 deaths per year in the United States. Most early stage renal cell carcinomas are successfully treated with surgery. Prognosis for patients with metastatic disease is generally poor, but advances in understanding the biology or renal cell carcinoma and antiangiogenic therapy have revolutionized the treatment of advanced renal cell carcinoma. The goals of the Centers clinical research program in renal cell carcinoma are to optimize the treatment for early stage renal cell carcinoma and to develop novel therapeutic approaches to treat advanced stage disease.

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 antiangiogenic 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 antiangiogenic therapy
• Determine whether novel biomarkers and/or tumor characteristics predict response to specific targeted therapies

Landmark bone study addresses debilitating side effect of prostate cancer treatment

Vertebral fractures in men receiving androgen-deprivation therapy for prostate cancer are associated with pain, loss of mobility, and decreased survival.

1 Smith MR, Lee H, Nathan DM
Insulin sensitivity during combined androgen blockade for prostate cancer.
J Clin Endocrinol Metab. 04/07/2006; 91(4); 1305-8.

2 Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR
Obesity and mortality in men with locally advanced prostate cancer: analysis of RTOG 85-31.
Cancer. 12/10/2007; 110(12); 2691-9.

3 Smith MR, Lee H, McGovern F, Fallon MA, Goode M, Zietman AL, Finkelstein JS
Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome.
Cancer. 05/05/2008; 112(10); 2188-94.

4 Michaelson MD, Smith MR, Talcott JA
Prostate cancer (metastatic).
Clin Evid. 11/23/2004; (10) 1012-22.

5 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. 09/19/2006; 24(27); 4457-63.

6 Talcott JA
Prostate cancer quality of life: beyond initial treatment and the patient.
J Clin Oncol. 09/19/2007; 25(27); 4155-6.