Genitourinary Cancers

In 2008, approximately 186,000 American men were diagnosed with prostate cancer, resulting in about 28,600 deaths.[1] It is the most commonly diagnosed cancer, and second only to lung cancer as the leading cause of cancer death in men.

The optimal treatment for clinically localized prostate cancer is an ongoing subject of controversy.[1] As pointed out by Drs. Mirhadi and Sandler, no randomized trial has compared radical prostatectomy (RP) to radiation therapy (RT), and no study has definitively “proven” the superiority of one technique over the other. Therefore, we disagree with the author’s conclusion that RT “is the ‘only way to go’ when managing early-stage prostate cancer.”

For the September and October issues of ­ONCOLOGY, we have assembled a team of experts in the diagnosis and management of early-stage prostate cancer-ie, disease that has not clinically metastasized at first presentation, and which is theoretically curable-and have asked them to take a position on optimal patterns of care.

Prostate cancer experts agree on one issue: No single treatment can be considered universal for men diagnosed with prostate cancer. There are myriad choices and considerations to be reviewed with every diagnosis. In addition, there are conflicting data about when, or if, men require screening for prostate cancer as well as when to start therapy for confirmed disease.

Patients with advanced renal cell carcinoma who were treated with sunitinib malate (Sutent) experienced a median overall survival of more than two years, compared with patients who took interferon-alpha, according to Pfizer.

Crawford and Hou[1] review the data on luteinizing hormone-releasing hormone (LHRH) antagonists in prostate cancer. They describe the results of a phase III trial comparing monthly degarelix to monthly leuprolide in men with advanced prostate cancer. Degarelix treatment was associated with a more rapid decline of serum testosterone, and was not associated with an initial surge of serum testosterone seen during the first few days of treatment with leuprolide. They discuss the role of this new form of medical gonadal suppression for the treatment of prostate cancer.

The recent US Food and Drug Administration (FDA) approval of degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, has renewed interest in this class of drugs as a prostate cancer therapy. Approval was based on a prospective phase III trial of 610 patients randomized to one of two dosing schedules of degarelix, or standard-of-care monthly leuprolide acetate monotherapy, with initial antiandrogen therapy allowed at the treating physician’s discretion for prevention of clinical flare.[1]

Drs. Crawford and Hou provide an important clinical introduction to a novel class of hormonal agents that have been under development for several decades for the treatment of advanced and metastatic prostate cancer.

Physicians have known since 1941 that testosterone suppression benefits patients with symptomatic metastatic prostate cancer.[1] The pioneering study in this regard showed that estrogen therapy achieved comparable efficacy to castration by improving acid and alkaline phosphatase levels associated with relief of cancer-related symptoms. More than 6 decades later, however, many of the therapies subsequently developed for achieving androgen deprivation still suffer from serious limitations.

The National Comprehensive Cancer Network (NCCN) has added everolimus (Afinitor) to the NCCN Guidelines for Kidney Cancer as a category 1 option for patients with metastatic renal cell carcinoma following failure of tyrosine kinase inhibitors such as sunitinib (Sutent) and sorafenib (Nexavar). This recommendation comes on the heels of the recent US Food and Drug Administration (FDA) approval of everolimus.

Aureon Laboratories has released Prostate Px, a test to predict prostate cancer regression and disease recurrence at the time of diagnosis. The technology combines molecular biomarkers, histological and clinical information with advanced mathematics, said Ricardo Mesa-Tejada, MD, vice president of pathology and medical director of Aureon Laboratories.

VIENNA-Image-guided intensity-modulated radiotherapy, high-intensity focused ultrasound, and cryotherapy are increasing the curative treatment options for men with prostate cancer. The problem is how to determine which patients are most suitable for these therapies.

Afinitor (everolimus) has been approved by the FDA for patients with advanced renal cell carcinoma after failure of treatment with sunitinib (Sutent) or sorafenib (Nexavar).

The US Food and Drug Administration (FDA) has approved everolimus (Afinitor) oral tablets for the treatment of patients with advanced kidney cancer whose disease has progressed after treatment with other cancer therapies. Everolimus is intended for patients with advanced renal cell cancer who have already tried another kinase inhibitor (sunitinib [Sutent] or sorafenib [Nexavar]).

SAN FRANCISCO-Studies show improved outcomes when androgen deprivation therapy (ADT) is part of the care for men with intermediate-risk prostate cancer, said Mack Roach III, MD, taking the “pro” side of a debate on the issue. But “con” speaker Arul Mahadevan, MD, argued that the studies in question included mostly high-risk patients, and that monotherapy is effective in intermediate-risk patients.

Polymedco, Inc, announced the availability of the BTA Stat test-a point of care technology for the early detection of recurrent bladder cancer. This method uses monoclonal antibodies to detect the presence of bladder tumor–associated antigen in urine. It is a single-step, rapid immunochromatographic assay for bladder tumor-associated antigen in voided urine.

Ferring Pharmaceuticals received approval from the US Food and Drug Administration (FDA) for degarelix, a new injectable gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for patients with advanced prostate cancer.

A study of nearly 1,500 patients treated for kidney cancer at UCLA in the past 15 years shows that an aggressive, tailored treatment approach results in better survival rates and uncovered subsets of kidney cancer that behave differently and need to be treated accordingly.

For men with locally advanced prostate cancer, the addition of radiation treatment to antiandrogen hormone therapy reduces the risk of dying of prostate cancer by 50% compared to those who have antiandrogen hormone treatment alone, according to a randomized study presented September 22, 2008, during the plenary session of the American Society for Therapeutic Radiology and Oncology’s 50th Annual Meeting in Boston.

Men over 70 years of age with early-stage prostate cancer have a 20% higher mortality if they are treated first with hormone therapy before being treated with radiation seed implants (brachytherapy), compared to men who are treated with brachytherapy alone, according to the largest cohort study of its kind presented September 23, 2008, at the 50th Annual Meeting of the American Society for Therapeutic Radiology and Oncology in Boston.

The advisory committee tothe UK’s National Health Service(NHS) has recommended that theNHS not pay for four new agentsproven effective in metastatic renalcell carcinoma. The four drugs arebevacizumab (Avastin), sorafenib(Nexavar), sunitinib (Sutent), andtemsirolimus (Torisel).

Patients with advanced renal cell carcinoma (RCC) treated with single-agent, oral sunitinib malate (Sutent) reported experiencing significantly lower severity of symptoms like bone pain and breathlessness, among others, than patients treated with interferon-alfa.

The lead investigator in an evaluation of bevacizumab (Avastin) combined with sunitinib malate (Sutent) for renal cell carcinoma (RCC) said the project would be abandoned. FDA issued a product safety alert after Genentech, Avastin’s developer, reported serious complications in several patients enrolled in the phase I trial.

A combination of two antiangiogenic agents-bevacizumab (Avastin) and thalidomide (Thalomid)-with docetaxel (Taxotere) is associated with a median progression-free survival of about a year and a half among men with metastatic, hormone-refractory prostate cancer, finds a phase II trial presented at ASCO 2008 (abstract 5000).

This is an expertly written summary of the experience with cryotherapy as primary treatment of prostate cancer and the rationale for proceeding toward more limited, organ-sparing approaches with this procedure as focal treatment for low-risk cancers. Growing evidence of overdetection and overtreatment in many men with low-risk tumors has resulted in the recognition that alternatives to conventional treatment strategies are needed. Observation, a laudable and appropriate approach, appeals to relatively few patients.

The article by Polascik and coauthors provides a timely synopsis of modern technologic advances in prostate cryoablation and a review of the rationale for and experience with targeted prostate treatments. Prostate cryoablation has a storied past, which can be briefly summarized as high excitement followed by near-complete abandonment. Fortunately, a few practitioners improved the technique and incorporated new technologies allowing for its resurrection.

Wyeth Pharmaceuticals recently announced the initiation of the INTORACT (INvestigation of TORisel and Avastin Combination Therapy) study, a worldwide randomized, open-label, phase IIIB study comparing temsirolimus (Torisel) plus bevacizumab (Avastin) vs bevacizumab plus interferon-alfa for first-line treatment of patients with advanced renal cell carcinoma (RCC). Wyeth Research is conducting the INTORACT study with the support and assistance of Roche and Genentech

CHICAGO-The combination of custir-sen sodium (OGX-011, OncoGenex Technologies Inc), an investigational agent, with docetaxel (Taxotere) or mitoxantrone has acceptable toxicity in patients with hormone-refractory prostate cancer who have experienced a failure of first-line docetaxel-based chemotherapy, investigators reported at ASCO 2008 (abstract 5002). Efficacy outcomes were somewhat better with the custirsen/docetaxel combination.

A multicenter study has found that the experimental targeted therapy everolimus (Cetican, RAD001) delays cancer progression in patients with metastatic kidney cancer that has progressed despite treatment with other targeted therapies. Lead author Robert J. Motzer, md, attending physician at Memorial Sloan-­Kettering Cancer Center, presented the results at the ASCO meeting (abstract LBA5026).

The first randomized trial to evaluate the long-term outcome of treatment with a single dose of chemotherapy for early-stage testicular tumors has found that the approach is safe, effective, and less toxic compared to radiation therapy, the current standard of care. The study, the largest ever in testicular cancer, also showed that after 5 years, patients receiving chemotherapy had a decreased risk of developing a second tumor in the other testicle, though longer follow-up is needed. The data were presented by R.T. Oliver, md, professor emeritus of medical oncology at St. Bartholomew’s Hospital in London and the study’s lead author, at the ASCO plenary session (abstract 1).