Kent E. Wallner, MD

Androgen deprivation therapy (ADT) has been used in the management of prostate cancer for more than four decades. Initially, hormone therapy was given largely for palliation of symptomatic metastases. Following several randomized trials of patients with intermediate- to high-risk prostate cancer that demonstrated improvements in biochemical control and survival with the addition of ADT to external beam radiotherapy, there was a dramatic increase in the use of hormone therapy in the definitive setting. More recently, the safety of ADT has been questioned, as some studies have suggested an association of hormone therapy with increased cardiovascular morbidity and mortality. This is particularly worrisome in light of practice patterns that show ADT use extrapolated to situations for which there has been no proven benefit. In the setting of dose escalation with modern radiotherapy, in conjunction with the latest concerns about cardiovascular morbidity with ADT, the magnitude of expected benefit along with potential risks of ADT use must be carefully considered for each patient.

Given the poor outcomes observed with radical prostatectomy (RP) and external-beam radiation therapy (EBRT), some in the urologic community contend that high-risk disease is not curable with currently available treatment strategies.[1,2] In fact, there is a growing contingent of clinicians who advocate the use of chemotherapy in conjunction with RP. With the established efficacy of brachytherapy, these efforts are likely excessive.

In the November 30, 2007, issue of ­ONCOLOGY, Dr. Tony S. Quang and colleagues have raised some very important and relevant issues regarding the costs and benefits of new technology in the treatment of prostate cancer ("Technologic Evolution in the Treatment of Prostate Cancer: Clinical, Financial, and Legal Implications for Managed Care Organizations," ONCOLOGY 21[13]:1598-1604, 2007).

Prostatic acid phosphatase (PAP) emerged as the world's first clinically useful tumor marker in the 1940s and 1950s. With the introduction of the prostate-specific antigen (PSA) test in the 1980s, which performed significantly better than PAP in terms of screening and monitoring response to treatment, PAP fell into disfavor. An increasing number of recent studies have identified PAP as a significant prognostic factor for patients with intermediate- and high-risk prostate cancer. PAP appears to be particularly valuable in predicting distant failure in higher-risk patients for whom high levels of local control are achieved with aggressive initial local treatment. As prostate cancer care becomes increasingly focused on identifying the minority of patients who would benefit from aggressive systemic therapy, a reevaluation of the potential contribution of the prostatic acid phosphatase test seems timely.

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States. Obesity is now linked with numerous health conditions, including many oncologic diagnoses. Its association with prostate cancer, the most prevalent cancer in men, has also been investigated, with studies suggesting a direct relationship between increasing obesity and prostate cancer mortality. Outcomes data for specific interventions in obese patients with prostate cancer have only recently begun to emerge. Surgery, while feasible even in the very obese, may result in less than optimal cancer control rates. Brachytherapy data are emerging, and are promising. No outcomes data are available for the use of external-beam radiation in obese patients. Long-term data for external-beam radiation, as well as for surgery and brachytherapy, are required to determine the most appropriate treatment for obese patients with prostate cancer. These data, coupled with a more thorough understanding of the biochemical relationship between obesity and prostate cancer, will be necessary to make optimal management decisions for obese patients with prostate cancer in the future.

Permanent prostate brachytherapy with or without supplemental therapies is a highly effective treatment for clinically localized prostate cancer, with biochemical outcomes and morbidity profiles comparing favorably with competing local modalities. However, the absence of prospective randomized brachytherapy trials evaluating the role of supplemental external-beam radiation therapy (XRT) has precluded the development of evidence-based treatment algorithms for the appropriate inclusion of such treatment. Some groups advocate supplemental XRT for all patients, but the usefulness of this technology remains largely unproven and has been questioned by recent reports of favorable biochemical outcomes following brachytherapy used alone in patients at higher risk. Given that brachytherapy can be used at high intraprostatic doses and can obtain generous periprostatic treatment margins, the use of supplemental XRT may be relegated to patients with a high risk of seminal vesicle and/or pelvic lymph node involvement. Although morbidity following brachytherapy has been acceptable, supplemental XRT has shown an adverse impact on long-term quality of life. The completion of ongoing prospective randomized trials will help define the role of XRT as a supplement to permanent prostate brachytherapy.

Following permanent prostatebrachytherapy with or withoutsupplemental external-beamradiation therapy, encouraging longtermbiochemical outcomes-includinga morbidity profile that comparesfavorably with competing local modalities-have been reported forpatients with low-, intermediate-, andhigh-risk features.[1,2] The efficacyand morbidity of prostate brachytherapyare dependent on implantquality. Substantial differences havebeen reported in the incidence andclinical course of brachytherapyrelatedmorbidities, with many of theconflicts likely related to patientselection, technical differences intreatment planning, intraoperativetechnique, or variation in patient managementphilosophies.[3-6]

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.

Payne, Coyne, and Smith present a concise review of the surprisingly meager literature regarding costs of end-of-life cancer care, an issue with substantial ethical and financial implications. They present evidence that improved coordination of care holds the potential to lower costs, or at least to offer better services at the same cost. The authors are to be commended for pursuing more rigorous studies regarding this difficult-to-quantify area of medical and social services. Moreover, they appropriately highlight the difficulties in attempting to capture direct costs of medical care and the far more elusive indirect costs.

The optimal management of patients with lymph node-positive prostate cancer remains controversial. The role of pelvic irradiation in patients at high risk for nodal involvement continues to be debated. Studies of prostate

Dr. Stock provides a thorough summary of recent data on the principal modes of treatment for early-stage prostate cancer. Prostatectomy, external radiation, and brachytherapy have all improved substantially over the last 15 years. Despite these improvements, however, it is still unclear how these modalities compare in terms of efficacy and morbidity. To provide some balance to his evenhanded approach, I will add a few remarks.