Prostate Cancer

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).

Despite a heightened focus of the medical and research community on prostate cancer, many important questions about this disease remain unanswered. These include questions about the possible prevention of prostate cancer, as well as the optimal treatment approaches for localized, locally advanced, metastatic, and hormone-refractory disease. A whole host of prospective, well-designed clinical trials are currently in progress that should answer many of these questions. This review briefly explores some of these unresolved issues and describes ongoing trials designed to address them. [ONCOLOGY 11(8):1-11, 1997]

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]

A prostate-specific antigen (PSA) nadir level of up to 1 ng/mL after three-dimensional conformal radiotherapy for patients with localized prostate cancer is a powerful prognostic variable, according to Dr. Michael Zelefsky of the Department of

No difference in the rates of biochemical failure was found between patients with stage T1 or T2 prostate cancer and a prostate-specific antigen (PSA) level of up to 10 ng/mL treated with radical prostatectomy and those treated with radiation

Newer radiation treatments--brachytherapy and conformal radiotherapy--were discussed at a symposium at the 1996 meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Los Angeles.

NEW ORLEANS--More evidence that diet may affect prostate cancer came from two presentations at the American Urological Association annual meeting.

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--Repeat biopsies enhance detection and improve the reliability of Gleason grading in the evaluation of prostate cancer, according to two reports from the American Urological Association annual meeting.

ASCO--In a randomized trial of patients with symptomatic refractory prostate cancer, chemotherapy plus prednisone provided significantly better pain control than prednisone alone; now, an economic analysis suggests that the combination was less expensive overall due to fewer hospital admissions.

Studies presented at the annual meeting of the American Urological Association (AUA) in New Orleans show positive results for the treatment of early-stage prostate cancer using brachytherapy or "seeding." The studies, conducted by Nelson

The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in

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.

NEW ORLEANS--For prostate cancer detection, the proportion of free PSA to total PSA, using a cut-off point of 25%, is more sensitive and specific than total PSA and avoids many unnecessary biopsies, according to a multicenter study presented at the American Urological Association (AUA) annual meeting.

The American Urological Association (AUA) recently urged Congress to pass the Medicare Preventive Benefit Improvement Act of 1997, which would provide coverage for annual prostate cancer screening for Medicare-eligible men over the age of

The American Urological Association (AUA) feels that the article by Johansson et al in the February 12th issue of the Journal of the American Medical Association, indicating comparable survival rates

Androgen blockade has potential applications beyond late-stage metastatic cancer of the prostate, according to Nelson N. Stone, md, Professor of Urology and Radiation Oncology at Mt. Sinai

Men whose metastatic prostate cancer is maintained in remission by complete hormonal therapy (CHT) with flutamide (Eulexin) and a luteinizing-hormone-releasing hormone (LHRH) agonist have a health-related quality of life (QOL) equal to

FORT LAUDERDALE, Fla--The key feature of prostate cancer that distinguishes it from most other solid tumors is the large discrepancy between annual incidence (about 250,000) and mortality (about 41,000).

Dr. Powell has written a comprehensive review of factors believed to contribute to the racial differences observed for prostate cancer incidence and mortality. Prostate cancer has a greater negative impact on African-Americans than on any other racial or ethnic group. However, the etiology of the striking racial variation in prostate cancer incidence and mortality remains enigmatic.

Dr. Powell is to be congratulated for an outstanding review article on prostate cancer in African-American men. As he points out, the age-adjusted incidence of prostate cancer in African-American (black) males is 50% higher than that in Caucasian (white) men, and black men have the highest incidence of prostate cancer in the world.[1] Differences between blacks and whites in the probability of being diagnosed with prostate cancer (9.6% vs 5.2%), lifetime prostate cancer-specific mortality (3% vs 1.4%), and 5-year survival (65% vs 78%) are all indicative of a major public health problem in the black male population.[2]

The article by Powell highlights uncertainties about the relative contributions of diagnostic delay and tumor biology to racial disparities in stage at diagnosis among American men with prostate cancer, and explores a variety of factors that may discourage early cancer detection in African-American men. Observations derived from our ongoing prospective studies of prostate cancer diagnosis and treatment outcomes in black and white American veterans and from our experience with prostate cancer screening at the University of Mississippi Hospital and Clinics afford additional insights into these issues and provide a framework for this commentary.

Mortality from prostate cancer is two to three times greater among African-American men between the ages of 50 and 70 than among American Caucasian men of similar ages. Also, African-Americans tend to present with more advanced tumors than their American Caucasian counterparts. This article explores differences between the two races that may account for the disproportionately high mortality among African-Americans and their more advanced disease stage at presentation. These include epidemiologic and histologic features of prostate cancer; clinical, biologic, and environmental factors; and barriers to health care. Various important issues that warrant further investigation are also highlighted. [ONCOLOGY 11(5):599-605, 1997]

FARMINGTON, Conn--Men with advanced prostate cancer who are in remission while on treatment with an LHRH agonist and flutamide (Eulexin) have a quality of life (QOL) that is similar to an equivalent norm for a matched population of US men without prostate cancer, say Peter C. Albertsen, MD, and his colleagues from Connecticut, Am-sterdam, and Boston.