Genitourinary Cancers

A temporary increase or "bounce" in the PSA level following radiotherapy of prostate cancer is a common occurrence and does not necessarily indicate increased risk that cancer will recur

The morbidities associated with prostate cancer treatments have improved over the years. However, potential overtreatment and the risks of adverse events associated with radical treatment still pose a considerable challenge. Targeted focal therapy (TFT) of prostate cancer appears to be part of a logical continuum in the quest to improve upon the management of early organ-confined disease. TFT is a procedure in which only the cancer in the gland is ablated. The normal gland, sphincter, and in most cases the neurovascular bundles are preserved. Therefore, this approach averts some of the common complications of more radical therapy. Initial experience has been encouraging; however, long-term data and full implementation of emerging advances in imaging are urgently needed before the widespread adoption of this approach. In this review, we present the current status of our knowledge about this procedure and the most important challenges that need to be addressed. We also present the initial results with this approach at our center.

Treating metastatic renal cell carcinoma (RCC) prior to surgery with Avastin (bevacizumab) and Tarceva (erlotinib) appears safe, effective, and may prolong patient survival, researchers reported at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (abstract 250). Although the two agents have been tested previously as postoperative treatment for the disease, the new data provide the first evidence that presurgical treatment with the drugs may improve patient outcomes.

Metastatic hormone-resistant prostate cancer has proven largely resistant to cytotoxic therapy. Since 2004, docetaxel (Taxotere)/prednisone has become the standard chemotherapy used to treat advanced hormone-resistant prostate cancer. However, the survival advantage is modest and a significant number of patients do not respond to chemotherapy. It is hoped that an increased understanding of the mechanisms underlying the progression of prostate cancer will lead to new treatment modalities. With the growing number of biologic and targeted agents under development, the potential armamentarium of prostate cancer treatments is steadily growing. However, none of the new treatment modalities has yet been shown to be more effective than standard treatments. This article will provide an overview of targeted or innovative therapies in the treatment of prostate cancer.

Results from a Southwest Oncology Group (SWOG) study show that radiotherapy given to men with locally advanced prostate cancer after their prostate gland is removed does not significantly reduce the risk of subsequent cancer spread to distant sites but significantly lowers the risk of the cancer recurrence compared to men who do not receive radiation.

Endocare, Inc, a medical device company focused on the development of minimally invasive technologies for tissue and tumor ablation, announced that six studies and papers demonstrating the effectiveness of cryoablation for treating renal cancer were published in a supplement to the July 2006 issue of Urology.

Metastatic hormone-resistant prostate cancer has proven largely resistant to cytotoxic therapy. Since 2004, docetaxel (Taxotere)/prednisone has become the standard chemotherapy used to treat advanced hormone-resistant prostate cancer. However, the survival advantage is modest and a significant number of patients do not respond to chemotherapy. It is hoped that an increased understanding of the mechanisms underlying the progression of prostate cancer will lead to new treatment modalities. With the growing number of biologic and targeted agents under development, the potential armamentarium of prostate cancer treatments is steadily growing. However, none of the new treatment modalities has yet been shown to be more effective than standard treatments. This article will provide an overview of targeted or innovative therapies in the treatment of prostate cancer.

For the past 20 years, the systemic treatment of metastatic renal cell carcinoma (RCC) has been limited primarily to cytokines, with few patients showing benefit. However, recent advances in understanding the pathobiology of RCC have led to the identification of novel therapeutic targets for this disease. Drugs specifically designed to inhibit these targets have been developed, with several showing superior efficacy over traditional cytokine therapy. Moreover, these agents are well tolerated and have improved the span of progression-free, and in some cases, overall survival. As a result, between December 2005 and January 2006, two of these targeted therapies—sunitinib (Sutent) and sorafenib (Nexavar)—were approved by the US Food and Drug Administration for the treatment of advanced RCC. The authors review the clinical trials that have focused on these two drugs as well as those concentrating on two other promising agents, bevacizumab (Avastin) and temsirolimus. The ways in which these novel drugs are changing the standard of care for metastatic RCC and the future directions of RCC clinical trials are also discussed.

Although testicular cancer is a rare disease accounting for only 1% of all male neoplasms, it represents a paradigm for cancer curability. Overall, more than 95% of patients can expect to be cured of their disease with minimal long-term toxicity. Given these expectations, it is critical that cancer care providers are familiar with the diagnostic and therapeutic challenges encountered in these rare patients. In particular, clinicians managing these patients should be aware of some of the pitfalls encountered when determining relapse. In a series of case presentations, we review the evaluation and management of patients with persistent elevation of serum tumor markers and postchemotherapy residual radiographic abnormalities.

Although testicular cancer is a rare disease accounting for only 1% of all male neoplasms, it represents a paradigm for cancer curability. Overall, more than 95% of patients can expect to be cured of their disease with minimal long-term toxicity. Given these expectations, it is critical that cancer care providers are familiar with the diagnostic and therapeutic challenges encountered in these rare patients. In particular, clinicians managing these patients should be aware of some of the pitfalls encountered when determining relapse. In a series of case presentations, we review the evaluation and management of patients with persistent elevation of serum tumor markers and postchemotherapy residual radiographic abnormalities.

Methylphenidate (Ritalin) effectively reduces fatigue in men with prostate cancer; however, careful monitoring is essential because the psychostimulant can also elevate blood pressure and pulse rates

The investigational agent lapatinib (Tykerb, GlaxoSmithKline) extended survival in the 61% of renal cell carcinoma (RCC) patients whose tumors overexpressed EGFR at the 3+ level

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States. Obesity is now linked with numerous health conditions, including many oncologic diagnoses. Its association with prostate cancer, the most prevalent cancer in men, has also been investigated, with studies suggesting a direct relationship between increasing obesity and prostate cancer mortality. Outcomes data for specific interventions in obese patients with prostate cancer have only recently begun to emerge. Surgery, while feasible even in the very obese, may result in less than optimal cancer control rates. Brachytherapy data are emerging, and are promising. No outcomes data are available for the use of external-beam radiation in obese patients. Long-term data for external-beam radiation, as well as for surgery and brachytherapy, are required to determine the most appropriate treatment for obese patients with prostate cancer. These data, coupled with a more thorough understanding of the biochemical relationship between obesity and prostate cancer, will be necessary to make optimal management decisions for obese patients with prostate cancer in the future.

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States. Obesity is now linked with numerous health conditions, including many oncologic diagnoses. Its association with prostate cancer, the most prevalent cancer in men, has also been investigated, with studies suggesting a direct relationship between increasing obesity and prostate cancer mortality. Outcomes data for specific interventions in obese patients with prostate cancer have only recently begun to emerge. Surgery, while feasible even in the very obese, may result in less than optimal cancer control rates. Brachytherapy data are emerging, and are promising. No outcomes data are available for the use of external-beam radiation in obese patients. Long-term data for external-beam radiation, as well as for surgery and brachytherapy, are required to determine the most appropriate treatment for obese patients with prostate cancer. These data, coupled with a more thorough understanding of the biochemical relationship between obesity and prostate cancer, will be necessary to make optimal management decisions for obese patients with prostate cancer in the future.

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States. Obesity is now linked with numerous health conditions, including many oncologic diagnoses. Its association with prostate cancer, the most prevalent cancer in men, has also been investigated, with studies suggesting a direct relationship between increasing obesity and prostate cancer mortality. Outcomes data for specific interventions in obese patients with prostate cancer have only recently begun to emerge. Surgery, while feasible even in the very obese, may result in less than optimal cancer control rates. Brachytherapy data are emerging, and are promising. No outcomes data are available for the use of external-beam radiation in obese patients. Long-term data for external-beam radiation, as well as for surgery and brachytherapy, are required to determine the most appropriate treatment for obese patients with prostate cancer. These data, coupled with a more thorough understanding of the biochemical relationship between obesity and prostate cancer, will be necessary to make optimal management decisions for obese patients with prostate cancer in the future.

The first large clinical trial to prospectively evaluate intermittent chemotherapy for androgen-independent prostate cancer showed that a minority of patients can be given chemotherapy "holidays" of clinically meaningful duration.

Two phase III international randomized trials of sunitinib (Sutent) and of the investigational mTOR kinase inhibitor temsirolimus indicate targeted therapy may provide both clinical and survival benefits to patients with advanced renal cell carcinoma (RCC). Sunitinib is an oral multi-targeted receptor tyrosine kinase inhibitor of the VEGF and PDGF receptors.

According to a new multicenter study, the drug sunitinib malate (Sutent) is more effective than the current standard cytokine treatment given as initial therapy for patients with metastatic renal cell carcinoma. The study was presented at the annual American Society of Clinical Oncology meeting in Atlanta.

In this review, we describe how clinical investigators addressed some of the challenges in prostate cancer chemotherapy trials 20 years ago, and we indicate what has evolved in the field since that time. We consider the impact that prostate-specific antigen measurement had in this setting, evolving clinical paradigms, multidisciplinary programs, and the current armamentarium of cancer treatment, including targeted molecular therapy, for patients with hormone-refractory disease.

In this review, we describe how clinical investigators addressed some of the challenges in prostate cancer chemotherapy trials 20 years ago, and we indicate what has evolved in the field since that time. We consider the impact that prostate-specific antigen measurement had in this setting, evolving clinical paradigms, multidisciplinary programs, and the current armamentarium of cancer treatment, including targeted molecular therapy, for patients with hormone-refractory disease.

In this review, we describe how clinical investigators addressed some of the challenges in prostate cancer chemotherapy trials 20 years ago, and we indicate what has evolved in the field since that time. We consider the impact that prostate-specific antigen measurement had in this setting, evolving clinical paradigms, multidisciplinary programs, and the current armamentarium of cancer treatment, including targeted molecular therapy, for patients with hormone-refractory disease.

Novel prognostic biomarkers for prostate cancer are moving toward the clinic and may eventually join Gleason score and other predictors of relapse to help with treatment decisions, according to data on two candidate markers presented at the 97th Annual Meeting of the American Association for Cancer Research.

A combination of radiation and suicide-gene therapy is eliminating the spread of prostate cancer; and providing a long-term vaccine against the disease, according to a study presented at the American Society of Clinical Oncology's annual prostate cancer meeting in San Francisco recently.

Cytogen Corporation recently announced the presentation of clinical data demonstrating that a high level of prostate-specific membrane antigen (PSMA) in prostate tissue is a strong predictor of prostate cancer recurrence. The data were presented at the 101st American Urological Association (AUA) Annual Meeting held May 20-25 in Atlanta.

The 5-year incidence of biochemical recurrence (BCR) of prostate cancer decreases with increased experience of the surgeon performing the prostatectomy, Fernando Bianco, MD, reported at the 2006 Prostate Cancer Symposium (abstract 272).

Socioeconomic factors predominantly explain racial and ethnic disparities in prostate cancer outcomes, according to a new study.

The US Food and Drug Administration (FDA) recently approved sunitinib malate (Sutent) capsules for two types of cancer: advanced renal cell carcinoma and malignant gastrointestinal stromal tumor (GIST), after disease progression on or intolerance to the frontline drug imatinib mesylate (Gleevec).

For the first time, the US Food and Drug Administration (FDA) has granted a new oncologic drug product approval for indications for two different cancers simultaneously. The agency approved Sutent (suniti-nib, Pfizer) for the treatment of patients with gastrointestinal stromal tumors (GIST) whose disease has progressed on imatinib (Gleevec) or who are unable to tolerate imatinib. It also granted Sutent accelerated approval for treating advanced renal cell carcinoma (RCC).

The Food and Drug Administration (FDA) has approved Nexavar (sorafenib tosylate) tablets for the treatment of patients with advanced renal cell carcinoma. Nexavar, a multikinase inhibitor that has been shown to double progression-free survival in these patients, is the first FDA-approved treatment for this type of cancer in more than a decade, Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc.

High-grade urothelial cancer ofthe bladder is not only relativelycommon but unfortunately,is frequently lethal. These tumorsare often diagnosed when thetumors have already invaded the wallof the bladder. Even when they arediagnosed at a time when they areconfined to the mucosa or lamina propria,patients may not respond to abladder-preservation approach. Oftena radical cystectomy with urinary diversionis either not offered at all or notconsidered until the cancer has invadeddeep into the muscularis propria andlocal treatment fails.