Prostate Cancer

Hormonal treatment of advanced prostate cancer should be consideredfor patients who have stages C and D1 disease, a high risk of recurrenceafter local therapy, or prostate-specific antigen–measured recurrenceafter local treatment. This approach is dependent on most prostatecancer cells being androgen-dependent, but androgen-independentcells may arise after several years of hormonal therapy. Options forandrogen blockade primarily include orchiectomy, luteinizing hormone–releasing agonists and antagonists, and nonsteroidal antiandrogens.There is some controversy regarding combined androgen blockade,intermittent androgen blockade, and the question of whether earlyandrogen blockade is superior to delayed therapy. Convincing data doexist for the use of adjuvant/neoadjuvant hormonal therapy with external-beam radiation therapy. Although hormonal therapy is an importanttreatment modality for advanced prostate cancer, long-termtreatment carries significant side effects that need to be considered.

For many years, prostate cancerhas been known to be sensitiveto androgens. Indeed, endocrinemanipulations aimed at the reductionof serum testosterone to below oraround the castrate range have beenthe mainstay in the management ofadvanced prostate cancer for the past60 years. Despite widespread testing,the advances with this treatment modalityfor prostate cancer over the pastseveral decades have been modest.Unfortunately, the answers to manyrelevant critical questions still lie inthe future. The limiting factor of hormonaltherapy is that a significant proportionof tumor cells are not affectedby androgen deprivation.

Oottamasathien and Crawfordadvance a hypothesis withwhich I heartily agree-androgendeprivation/antagonist (AD/A)strategies should be considered in manymore patients than urologists and oncologiststraditionally teach. However,I think the authors could substantiallysharpen their message. I would like tomake five specific points, and thenoffer a few nitpicking comments.

CHICAGO-Zoledronic acid (Zometa) significantly decreased skeletal complications and bone pain in men with hormone-refractory prostate cancer and bone metastases, compared with placebo, according to an update of a phase III study presented at the 2003 Annual Meeting of the American Urological Association (abstracts 1472 and 1473).

The US Preventive Services Task Force has concluded that notenough scientific evidence exists to promote routine screening ofall men over age 40 for prostate cancer via standard prostatespecificantigen test and/or digital rectal exam. The task force-sponsoredby the Agency for Healthcare Research and Quality-concludedthat the tests are effective for diagnosis but that there is insufficientevidence to show that they affect long-term health or survival. The taskforce noted that results of the ongoing Prostate, Colorectal, Lung, andOvarian Screening Trial, designed to answer this question, will notbecome available until later in this decade.

CHICAGO-Black men with localized prostate cancer do just as well as white men when treated with brachy-therapy alone, William Barrett, MD, said at the 88th Annual Scientific Assembly of the Radiological Society of North America (RSNA abstract 252RO-p).

BETHESDA, Maryland-Astra-Zeneca failed to gain backing from the FDA’s Oncologic Drugs Advisory Committee (ODAC) for its effort to expand the indication for Casodex (150 mg bicalutamide) in the treatment of prostate cancer. ODAC members found that the data presented were too premature to recommend that the FDA approve the company’s supplementary new drug application. They suggested, instead, that the agency delay a decision until longer-term data about the drug’s efficacy become available.

ROCKVILLE, Maryland-The US Preventive Services Task Force has concluded that not enough scientific evidence exists to promote routine screening of all men over age 40 for prostate cancer via standard PSA test and/or digital rectal exam. The task force-sponsored by the Agency for Healthcare Research and Quality-concluded that the tests are effective for diagnosis but that there is insufficient evidence to show that they affect long-term health or survival. The task force noted that results of the ongoing Prostate, Colorectal, Lung, and Ovarian Screening Trial, designed to answer this question, will not become available until later in this decade.

NEW YORK-In patients with androgen-independent prostate cancer, a pulsed regimen of docetaxel (Taxotere) plus high-dose calcitriol is well tolerated and results in disease response by a variety of standard measures, according to results of a phase II trial.

A6-year prostate cancer research plan released by the NationalInstitutes of Health (NIH) contains a detailed outline of theNational Cancer Institute’s (NCI) future strategy for dealingwith the disease, which includes a shift in the standard treatment modelfrom seek-and-destroy to target-and-control.

BETHESDA, Maryland-A 6-year prostate cancer research plan released by the National Institutes of Health (NIH) contains a detailed outline of the National Cancer Institute’s (NCI) future strategy for dealing with the disease, which includes a shift in the standard treatment model from seek-and-destroy to target-and-control.

NEW YORK-Urologic surgeons at Beth Israel Medical Center are turning for help to a robot "assistant" that makes the difficult and time-consuming procedure of laparoscopic radical prostatectomy easier and more efficient.

Erectile dysfunction is a common sequela following potentiallycurative local treatment for early-stage carcinoma of the prostategland. With larger studies and longer follow-up, it is clear that erectiledysfunction following prostate brachytherapy is more common thanpreviously reported, with a myriad of previously unrecognized sexualsymptoms. Approximately 50% of patients develop erectile dysfunctionwithin 5 years of implantation. Several factors including preimplantpotency, patient age, the use of supplemental external-beam irradiation,radiation dose to the prostate gland, radiation dose to the bulb ofthe penis, and diabetes mellitus appear to exacerbate brachytherapyrelatederectile dysfunction. The majority of patients with brachytherapy-induced erectile dysfunction respond favorably to sildenafil citrate(Viagra). Despite reports questioning the potency-sparing advantageassociated with brachytherapy, recent elucidations of brachytherapyrelatederectile dysfunction may result in refinement of treatmenttechniques, an increased likelihood of potency preservation, andultimately, improved quality of life.

The article by Drs. Merrick,Wallner, and Butler providesan excellent overview of issuespertaining to sexual dysfunctionfollowing prostate brachytherapy.The authors were the first to addressthe historical and current problemswith diagnosing sexual dysfunction.They make a strong case for developinga quality-of-life (QOL) instrumentthat is specific for prostatebrachytherapy.

Over the past decade, prostatebrachytherapy has been usedincreasingly as definitivetreatment for early-stage carcinomaof the prostate gland, with the majorityof the literature on brachytherapyreporting biochemical results as favorableas those in the most positiveradical prostatectomy and externalbeamradiation therapy series.[1-4]Because of a lack of definitive evidencesupporting the efficacy of onelocal treatment approach over another,quality-of-life (QOL) parametershave assumed greater importance. Ithas been widely asserted that preservationof potency is more likely followingbrachytherapy, but longerfollow-up has raised substantialdoubts about brachytherapy’s potency-sparing advantage.[5,6] In addition,brachytherapy results in amyriad of previously unrecognizedeffects on sexual function.[7,8]

The current ONCOLOGY articleby Drs. Merrick, Wallner,and Butler is a valuable additionto the literature. An estimated189,000 American men were diagnosedwith prostate cancer in 2002,and 30,200 died of the disease, makingit the most common cancer amongmen, and the second most commoncause of cancer death.[1] The treatmentshave led to a high rate of cure,but the results of treatment oftencause a reduction in quality of life.

NEW ORLEANS-In the treatment of localized prostate cancer, biochemical failure rates are similar among permanent radioactive seed implantation, high-dose external beam radiation therapy, combination seeds/external radiation, and radical prostatectomy, according to a very large series of patients followed at the Cleveland Clinic Foundation and Memorial Sloan-Kettering Cancer Center.

NEW ORLEANS-Radioactive seed implantation alone continues to prove effective in low-risk prostate cancer, but optimal dose is important in achieving a good outcome, according to a report from Mount Sinai School of Medicine, New York, presented at the American Society for Therapeutic Radiology and Oncology (abstract 55).

The addition of high-dose calcitriol (the active form of vitamin D) to weekly treatment with docetaxel (Taxotere) appears to improve response in men with hormone-refractory prostate cancer without compromising safety, according to the results of a

William Pirl and Jeffrey Mello present an informative overview of the psychological impact of prostate cancer. They also provide a practical framework for distress management, as promulgated by the National Comprehensive Cancer Network (NCCN).

The authors challenge the notion that men with prostate cancer exhibit little psychological difficulty. In fact, we do not know much about actual distress rates in men with prostate cancer because few studies have directly measured distress in this population. Likewise, we do not know if the distress experienced by prostate cancer patients is qualitatively different from that of other cancer patients. By assuming that all men with prostate cancer "do well," we, as clinicians and researchers, may fail to ask patients important questions.

Over the past decade, interest has been growing in the quality of life of men with prostate cancer. Traditionally considered a group with few psychological complications, 10% to 20% of men with prostate cancer are found to have clinically significant levels of psychological distress. This article reviews the prevalence of psychiatric symptomatology among prostate cancer patients, the psychological challenges of coping with the disease, and general guidelines for treatment. [ONCOLOGY 16:1448-1467, 2002]

Pirl and Mello carefully review the current state of knowledge about the psychological complications of prostate cancer. Their discussion is worth reading, particularly by those who treat patients with the disease. To put this knowledge in context for the general reader, we should give some thought to what this review illustrates about all patients with a serious life-threatening illness.

African-American patients with advanced prostate cancer survived slightly longer than white patients, according to a multi-institutional study led by Dana-Farber Cancer Institute researchers. The findings, which were reported at the 38th annual

UPPSALA, Sweden-In a new study, radical prostatectomy reduced deaths due to prostate cancer but did not increase overall survival in men with newly diagnosed, early-stage disease. The Scandinavian Prostatic Cancer Study Group found that after a median 6.2 years of follow-up, there were no significant differences in overall survival, but patients randomized to radical prostatectomy were less likely to develop distant metastases than those randomized to watchful waiting.