Genitourinary Cancer

Our Clinical Trials Continually updated listing of our clinical trials for genitourinary cancers more

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:

Detection, Diagnosis, and Prognosis

• Our team integrates molecular analysis with clinical parameters and uses statistical modeling to build more powerful aids for selecting therapy and predicting outcome. We defined factors to identify men with localized prostate cancer who can safely defer treatment. New predictive models can now estimate the probability of cancer recurrence within 10 years of radical prostatectomy, the probability of metastatic spread for patients with recurrence, and the probability of death following progression on hormonal therapy. See Prostate Nomograms for access to our online calculator. J Natl Cancer Inst 2006;98:715-717. [PubMed Abstract]

• Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) have substantial value in staging. Specifically, our investigators have demonstrated in large studies (of more than 300 patients) that MRI and MRSI contribute significant incremental value to clinical variables and clinical staging nomograms in the prediction of extracapsular extension and seminal vesicle invasion in prostate cancer. MRI can detect cancer in the transition zone as well as recurrent disease. We have also demonstrated the importance of sub-specialization in image interpretation and the utility of MRI for improving surgical planning. In addition, we have learned that MRI/MRSI can provide an indication of tumor aggressiveness and can contribute incremental value to nomograms for the prediction of indolent cancer. Radiology 2006;239:784-792. [PubMed Abstract]; Radiology 2006;238:176-183, 2006. [PubMed Abstract]; Radiology 2005;234:804-814. [PubMed Abstract]

• Our studies of patients with germ cell tumors (GCT) have revealed factors that predict outcomes after retroperitoneal lymph node dissection (RPLND) for patients with stage I-II nonseminomatous GCT. We have identified subgroups of patients with clinical stage I-IIA embryonal cell histologies and vascular invasion who can be managed with RPLND alone. Our studies in the 1990s established the utility of the i(12p) chromosome as a diagnostic tool that reliably distinguishes GCT from other poorly differentiated cancers. More recently, we showed that gain at 12p is associated with activation of proliferation and re-establishment or maintenance of stem-cell function. Our investigators developed a 146-gene expression classifier that correctly predicted the major histological component of these often heterogeneous tumors in more than 90 percent of cases. Further analysis yielded a 74-transcript classifier for outcome that was confirmed in a validation set. A prospective clinical assessment of these markers is now underway. The expression of three genes correlated highly with resistance, and two correlated highly with response are serving as the basis for studies of function and the development of paraffin-based markers. Cancer Res 2006;66:820-827. [PubMed Abstract]; Oncogene 2005;24:5101-5107. [PubMed Abstract]

• A new nomogram extends our prior work on prognostic models, predicting the likelihood of recurrence of clear-cell renal carcinoma after nephrectomy and survival of previously treated patients. The distinct histological subtypes of this disease are biologically unique. A set of three antigens (AMACR, CK7, and CD57) usefully distinguishes papillary renal cell carcinoma (RCC) from the morphologically similar metanephric adenoma. Collaborative efforts are now investigating the molecular profile of response to therapy by expression profiling of RCC samples resected from patients treated with sunitinib, and analysis of expression profiles of sunitinib-sensitive and sunitinib-resistant RCC cell lines. The studies may lead to more rational therapeutic selection. J Urol 2005;173:48-51, 2005. [PubMed Abstract]; Mod Pathol 2006;19:218-224. [PubMed Abstract]

• Building on extensive therapeutic and pharmacodynamic studies with single-photon emitters, our nuclear medicine specialists have embarked on PET tracer studies of antibodies to improve the dosimetry of targeted therapy and in vivo immunotyping. Clinical trials with positron-emitting antibodies (¹²⁴I-G250, and ¹²⁴I -A33) are underway. The ability to define tumor histology with imaging tools appears promising for planning surgery for renal cancer.

• A number of our groups are investigating molecular techniques for the detection of small numbers of tumor cells, in an effort to gauge the completeness of response to therapy and the probability of disease relapse. Efforts to detect circulating bladder cancer cells have found that a nested RT-PCR assay for the urothelial-cell-specific uroplakins UPIa and UPII provides the best sensitivity (75 percent) and predictive value (81 percent). The assay will be included in our systemic therapy clinical trials in bladder cancer.

Therapeutic Approaches

• Our investigators showed that sunitinib, a small molecule tyrosine kinase inhibitor, is safe and effective for treating advanced renal cell tumors. The drug received approval by the U.S. Food and Drug Administration for this indication in 2006. J Clin Oncol 2006;24:16-24, 2006. [PubMed Abstract]; JAMA 2006;295:2516-2524. [PubMed Abstract]

• Other studies we conducted found that a persistently increased AFP and/or HCG level after orchiectomy in patients with nonseminomatous GCT is highly associated with distant metastatic disease, leading to the administration of chemotherapy as initial therapy even in patients with clinical stage I and IIA disease. Administration of etoposide and cisplatin (without bleomycin), equivalent to a bleomycin-containing regimen in a randomized trial performed here, cured 87 out of 88 patients (99 percent) when used as adjuvant chemotherapy after RPLND; the one patient who relapsed was cured with salvage chemotherapy. The treatment also yielded a 95 percent five-year survival rate among 289 patients with metastatic GCT who were considered to be good risk. Paclitaxel-containing salvage therapy is now widely used in those patients relapsing after a complete response, with a 70 percent complete remission rate; with high-dose therapy given to patients without a prior complete response rate, we observed a durable complete response rate of 50 percent. J Clin Oncol 2005;23:2781-2788. [PubMed Abstract]; J Clin Oncol 2005;23:9290-9294. [PubMed Abstract]; J Clin Oncol 2005;23:6549-6555; Proc ASCO, 2006. [ASCO Abstract]

Delivery of Care

• We led a study showing a strong association between the type of physician seen and the kind of therapy received by men with localized prostate cancer. For example, men aged 65 to 69 more frequently had radical prostatectomy when evaluated exclusively by a urologist (70 percent), whereas most men older than 75 chose watchful waiting or hormone therapy if they saw only a urologist (91 percent). In contrast, all men, regardless of age, more frequently received radiation therapy when evaluated by both a urologist and radiation oncologist (78 percent of the younger men and 85 percent of the older men). Differences also were seen if men saw both a urologist and medical oncologist, and if they saw all three specialists. J Natl Cancer Inst 2007 Aug. [PubMed Abstract]