Genitourinary Cancer -- Clinical Research Program

Clinical research in genitourinary cancer includes study of diseases of the prostate, bladder, kidney, testis, and related organs such as the penis, retroperitoneum, and adrenal glands. The genitourinary research team includes experts in urology, radiation oncology, chemotherapy, immunotherapy, pathology, and radiology. In addition, Memorial Sloan Kettering Cancer Center experts in computer science and outcomes research are developing computerized tools called nomograms that assist patients in making treatment decisions.

Our investigators have been at the forefront of research evaluating the latest surgical techniques, increasingly targeted radiation treatments, novel chemotherapy agents, and hormonal and immunologic approaches.

Among our recent research accomplishments:

Molecular Pathology

  • We have demonstrated that B7-H3 and B7x, believed to be negative regulators of peripheral immune responses, are overexpressed in more than 90 percent of prostate tumors, and high-level expression is associated with cancer recurrence and cancer-specific death. Proc Natl Acad Sci. 2007 Dec 4;104(49):19458-63. [PubMed Abstract]
  • Our team has shown that circulating tumor cells isolated from patients with prostate cancer have molecular features of metastatic epithelial cells and are associated with prognosis. Clin Cancer Res. 2007 Apr 1;13(7):2023-9. [PubMed Abstract]; Clin Cancer Res. 2007 Dec 1;13(23):7053-8. [PubMed Abstract]
  • Other studies have shown that measurement of prostate kallikreins and other proteases can be used to determine prostate cancer risk and prognosis years before a diagnosis. J Clin Oncol. 2007 Feb 1;25(4):431-6. [PubMed Abstract]; J Clin Oncol. 2007 Feb 1;25(4):347-8. [PubMed Abstract]
  • Our pathologists have found that carbonic anhydrase IX expression, the target of the G250 antibody currently in clinical development, is highly expressed on the majority of clear cell renal cell carcinomas, a finding confirmed in vivo in a neoadjuvant trial with iodine-124-labeled antibody chimeric G250 and positron emission tomography in patients with renal masses. Am J Surg Pathol. 2008 Mar;32(3):377-82. [PubMed Abstract]; Lancet Oncol. 2007 Apr;8(4):304-10. [PubMed Abstract]
  • We have identified a four-gene signature associated with interferon resistance in renal cell carcinoma. J Urol. 2007 Apr;177(4):1264-8; discussion 1268. [PubMed Abstract]

Imaging

  • Our team has shown that magnetic resonance imaging (MRI) and spectroscopy have utility for predicting insignificant prostate cancer. BJU Int. 2007 Apr;99(4):786-93. [PubMed Abstract]
  • We have demonstrated that imaging features and the degree of enhancement of renal cortical tumors on computed tomography can help differentiate tumor subtypes. Radiology. 2007 Aug; 244(2):494-504. [PubMed Abstract]
  • We have also shown that endorectal MRI improves prediction of seminal vesicle invasion in prostate cancer. Radiology. 2007 Jan;242(1):182-8. [PubMed Abstract]
  • A study by Memorial Sloan Kettering radiologists showed that MRI reveals clinically significant local recurrence of prostate cancer after radiotherapy occurs at the site of the primary tumor. Int J Radiat Oncol Biol Physi. 2007 Sep 1;69(1):62-9. [PubMed Abstract]

Local and Regional Treatment

  • A multidisciplinary study conducted at Memorial Sloan Kettering showed that predictions about prognosis in men with castration-resistant prostate cancer can be made by measuring circulating tumor cells. Such measurements can help physicians in making treatment decisions and facilitate clinical studies. Lancet Oncol. 2009 Mar; 10(3):233-9. [PubMed Abstract]

New Agents

  • In an attempt to improve viral delivery of potentially therapeutic genes via an intravesical route, we have recently developed murine leukemia virus-based replication-competent retrovirus (RCR) vectors. Intravesically administered RCR vectors can efficiently deliver genes to orthotopic bladder tumors in mice without viral spread in distant organs. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4511-8. [PubMed Abstract]
  • We found the decision to conduct a phase III trial can be more reliably informed by methods that better use historical data and individual patient-risk profiles. Clin Cancer Res. 2007 Feb 1;13(3):972-6. [PubMed Abstract]; Med Decis Making. 2007 Jul-Aug;27(4):380-6. [PubMed Abstract]
  • A committee of investigators experienced in conducting trials for prostate cancer, the Prostate Cancer Clinical Trials Working Group (PCWG2), which includes members of Memorial Sloan Kettering's genitourinary team, defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Guidelines for clinical trial conduct in patients with metastatic prostate cancer were developed. The PCWG2 recommends increasing emphasis on time-to-event end points (such as failure to progress) as decision aids in proceeding from phase II to phase III trials. J Clin Oncol. 2008 Mar 1;26(7):1148-59. [PubMed Abstract]
  • A multicenter study led by Memorial Sloan Kettering researchers showed that an experimental drug lowers prostate-specific antigen levels in men with advanced prostate cancer. Investigators studied two novel compounds, RD162 and MDV3100, and gained not only an understanding of their novel mechanism of action, but found that these agents showed activity in an aggressive form of the disease called castration-resistant prostate cancer. Science. 2009 May 8;324(5928):787-90. [PubMed Abstract]

Targeted Therapies

  • We participated in a multicenter phase III trial that that compared interferon alfa to temsirolimus — an inhibitor of mammalian target of rapamycin (mTOR). As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival. N Engl J Med. 2007 May 31; 356(22):2271-81. [PubMed Abstract]
  • We led a multicenter, randomized phase III trial that enrolled 750 patients with previously untreated, metastatic renal cell carcinoma. The results showed that compared to interferon alfa, sunitinib, a receptor tyrosine kinase inhibitor, is associated with higher objective response rate, longer progression-free survival, and better quality of life in patients with metastatic renal cell cancer. N Engl J Med. 2007 Jan 11;356(2):115-24. [PubMed Abstract]
  • We participated in a phase II trial of axitinib, a selective inhibitor of VEGF receptors, which showed it has clinical activity in patients with cytokine-refractory metastatic renal cell cancer. Lancet Oncol. 2007 Nov; 8(11):975-84. [PubMed Abstract]

Immunotherapy

  • Our study demonstrated that MLN2704, an immunoconjugate between an antimicrotubule agent and a monoclonal antibody to prostate-specific membrane antigen (PSMA), is well tolerated in repetitive dosing in patients with advanced prostate cancer. J Clin Oncol. 2008 May 1;26(13):2147-54. [PubMed Abstract]
  • We conducted a phase I evaluation of indium-111-labeled J591, a monoclonal antibody targeted at PSMA expressed on tumor neovasculature, and demonstrated that it is well tolerated and shows selective targeting to tumors. J Clin Oncol. 2007 Feb 10;25(5):540-7. [PubMed Abstract]; Clin Cancer Res. 2007 May 1;13(9):2707-13. [PubMed Abstract]

Chemotherapy

  • Our team showed that dose-intense chemotherapy consisting of paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide is effective and tolerated in patients with high-risk progressive germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. [PubMed Abstract]
  • In a randomized phase III trial, our team investigated the role of high-dose chemotherapy as first-line treatment in patients with metastatic germ cell tumors and poor-prognostic clinical features. We showed that first-line high dose chemotherapy does not improve outcomes for patients with poor-risk nonseminomatous germ cell tumors. J Clin Oncol. 2007 Jan 20;25(3):247-56. [PubMed Abstract]
  • Two studies by our group using data obtained from our prospective surgical database and a multivariable logistic regression model have shown that effective chemotherapy combined with aggressive post-chemotherapy surgery improves outcomes for men with metastatic nonseminomatous germ cell tumors. J Clin Oncol. 2007 Dec 10;25(35):5603-8. [PubMed Abstract]; J Clin Oncol. 2007 Mar 20;25(9):1033-7. [PubMed Abstract]

Symptom Control and Quality of Life

  • Members of our team found that erectile function appears to have the strongest association with sexual satisfaction; however, variables such as relationship quality, depression, and anxiety are also clearly related to a satisfying sex life. J Sex Med. 2007 Sep; 4(5):1422-7. [PubMed Abstract]
  • We used results from a cavernous nerve injury animal model to demonstrate that sildenafil preserves erectile function by maintaining smooth muscle and endothelial function and by reducing apoptosis. J Sex Med. 2008 May;5(5):1126-36. [PubMed Abstract]
  • We found that protective effects of FK506 are dose and schedule dependent. J Sex Med. 2008 Jun;5(6):1334-44. [PubMed Abstract]