Genitourinary Cancers

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]

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

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--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.

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

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.

This paper is a very nice review of the history of the development of modern urologic surgical procedures for the treatment of testicular germ-cell tumors and their current indications. I agree with virtually everything the authors say. I will emphasize several points that they make and highlight a few small areas of disagreement.

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 Drs. Steele and Richie is a well-written, extremely important review of the natural history, treatment options, and current role of surgery in the management of nonseminomatous germ cell tumors of the testis. The authors present their rationale for retroperitoneal lymph node dissection (RPLND) in a thoughtful and provocative way. Their philosophy mimics that practiced at the University of Southern California (USC), which is very similar to that espoused by Drs. John Donohue and Larry Einhorn, who pioneered the current management practices that have made germ cell testicular tumors the most curable solid tumor in humans.[1,2]

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.

Carcinoma of the testis is the most common malignancy in males 15 to 35 years of age. Testicular cancer has become one of the most curable solid neoplasms and, as such, serves as a paradigm for the multimodality treatment of malignancies. The cure rate for patients with clinical stage I disease is nearly 100%, and patients with advanced disease now achieve complete remission rates of over 90%. The markedly improved outlook for patients with this cancer over the past 15 years has led to a reassessment of management options, especially in patients with clinical stage I disease. The realization that platinum-based chemotherapy could cure most patients with an advanced nonseminomatous germ cell tumor (NSGCT), especially those with minimal disease, led to the introduction of various strategies to decrease the morbidity associated with surgical management. These strategies include surveillance protocols, chemotherapy for clinical stage II disease, and observation protocols for a subset of patients with advanced disease who have had a partial response to chemotherapy. Retroperitoneal lymph node dissection (RPLND) has an important place in the management of both low- and high-stage testicular cancer. It offers the patient two basic benefits: accurate staging and the possibility of a surgical cure, even in the presence of metastatic disease. [ONCOLOGY 11(5):717-729, 1997]

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]

Progress in managing testicular cancer over the last 2 decades has produced survival rates of well over 90% using a multidisciplinary approach that serves as a model for other tumors. Improved imaging techniques permit more accurate clinical staging, allowing the clinician to select, for each patient, the sequence of surgical and chemotherapeutic modalities that maximizes survival while keeping morbidity within tolerable limits. Current investigators are attempting to refine treatment protocols so as to maintain or improve survival while reducing morbidity and costs.

In a lively session featured at the 32nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Jerome P. Richie, md, Brigham and Women's Hospital, Boston, and Steven H. Woolf, md, mph, Medical College of Virginia,

Dr. DeAntoni has carefully reviewed the literature on age-specific reference ranges for prostate-specific antigen (PSA) in the diagnosis of prostate cancer and the controversy surrounding their use. Key to understanding of this debate are two fundamental concepts: (1) the definition of "clinically significant prostate cancer" and (2) the use of sensitivity and specificity, which is frequently obscured by the surrounding rhetoric. The assumption that all readers uniformly interpret the meaning of clinically significant prostate cancer and wish to achieve the same results by manipulating sensitivity and specificity is probably incorrect.

PSA is the best tumor marker yet discovered. Age-specific reference ranges could improve the sensitivity of PSA by detecting curable, organ-confined tumors.

Controversy exists over the optimal management of patients with an asymptomatic rising prostate-specific antigen (PSA) following definitive therapy for clinically localized prostate adenocarcinoma.