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Genitourinary Cancers

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NEW ORLEANS-Emerging strategies for treatment of advanced prostate cancer rest on precise classification of the hormone status of the disease and a range of developing techniques and agents aimed at increasing survival, according to experts at the 92nd Annual Meeting of the American Urological Association.

MENLO PARK, Calif-In preclin-ical studies, an attenuated adenovirus engineered to incorporate the regulatory region of the PSA gene has been shown to selectively infect and destroy human prostate cancer cells expressing PSA. The engineered virus, named CN706, was developed by scientists from Calydon, Inc., a California-based biopharmaceutical firm, and the Brady Urological Institute at The Johns Hopkins Oncology Center.

As described by Wilt et al in their review, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) is asking very important questions about the effect of surgical treatment vs observation, with delayed androgen deprivation available to both groups, in patients with localized prostate cancer. Clinicians who have suffered with the old Uro-Oncology Trial comparison of prostatectomy vs radiation hope that PIVOT provides answers rather than confusion.

NEW ORLEANS--The inheritance pattern for prostate cancer is becoming better understood by linkage analysis, and it appears that the inherited form may be more aggressive than sporadic cancer, according to reports at the American Urological Association meeting.

CHICAGO--When physicians squared off on the issue of brachytherapy (interstitial radioactive seed placement) for prostate cancer at the Prostate Cancer Shootout II conference, the lines could not have been drawn more clearly.

The Genitourinary (GU) Cancer Committee of the Southwestern Oncology Group (SWOG) has achieved repeated successes in conducting prospective studies of prostate cancer. This article is a summary of recently completed and current trials in prostate cancer and, as such, represents an intriguing snapshot of priorities in prostate cancer clinical trials in 1997.

In 1941, Charles Huggins, Clarence Hodges, and R. E. Stevens reported on the beneficial effects of orchiectomy in 21 men with advanced prostate cancer.[1] Fifty-five years later, Southwest Oncology Group (SWOG) investigators were able to confirm, in a 1,387-patient intergroup comparative trial of bilateral orchiectomy with or without flutamide (Eulexin), that we still have nothing better to offer these men. This fact alone should underscore the critical need for well-planned, well-executed clinical trials in prostate cancer. The incidence and death rates continue to rise, and even today too few men are being enrolled in studies designed to alter these statistics.

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) should prove interesting in that the study design will permit observation of the natural history of a potentially lethal malignant disease, influenced only by palliative treatments. My comments will focus on the concerns raised by this study design. I will not address possible biases of the trial introduced by: (1) enrollment of less than 20% of the eligible population; (2) an enrollment rate per participating center of less than 3 patients per year; (3) a 7-year enrollment period; and (4) a 12-year follow-up (for a total trial duration of 19 years).

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized trial designed to determine whether radical prostatectomy or expectant management provides superior length and quality of life for men with clinically localized prostate cancer. Conducted at Department of Veterans Affairs and National Cancer Institute medical centers, PIVOT will enroll over 1,000 individuals less than 75 years of age. The primary study end point is all-cause mortality. Secondary outcomes include prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness. Within the first 3 years of enrollment, over 400 men have been randomized. Early analysis of participants' baseline characteristics indicate that enrollees are representative of men diagnosed with clinically localized prostate cancer throughout the United States. Therefore, results of PIVOT will be generalizable. These results are necessary in order to determine the preferred therapy for clinically localized prostate cancer. [ONCOLOGY 11(8):1133-1143, 1997]

The changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies. [ONCOLOGY 11(8):1155-1170, 1997]

PALM BEACH, Fla--With more early-stage prostate cancers being detected, and with growing demand from patients, use of brachytherapy in prostate cancer is expected to increase substantially over the next decade, John C. Blasko, MD, said at the American Brachytherapy Society meeting.

NEW ORLEANS--The enzyme telomerase is detectable in the majority of bladder washings from patients with bladder cancer, making it a reliable marker for cancer, according to several reports presented at the American Urolog-ical Association (AUA) annual meeting.

NEW ORLEANS--A large SWOG study presented at the American Urology Association (AUA) meeting confirms the efficacy of Bacillus Calmette-Guerin (BCG) as maintenance therapy for superficial bladder cancer, and a report from Italy shows its benefits as an adjuvant to surgery.

Gene therapy for prostate cancer faces hurdles similar to those being encountered for other cancers and nonmalignant processes. The greatest obstacle is the identification of efficient delivery systems, since numerous animal models and cell culture systems have shown potential efficacy when most cells express the introduced genetic material. Early prostate cancers are easily accessible to gene vector introduction, and the predictable metastatic patterns of this cancer may offer additional advantages for gene therapy. This article reviews gene vectors and gene products, as well as ongoing trials of gene therapy that have recently begun in prostate cancer. [ONCOLOGY 11(6):845-856, 1997]

The explosive increase in the apparent incidence of prostate cancer in the United States (which is due, in large measure, to wider efforts at early detection) has been accompanied by a dramatic stage migration, which can also be attributed to the increased use of prostate-specific antigen (PSA).

ASCO--An oral drug that blocks enzymes that appear to be fundamental for tumor spread significantly slowed the rate of rise of PSA in men with advanced hormone-refractory prostate cancer and may have the potential to increase survival, Peter Boasberg, MD, reported at the ASCO meeting.