Gregory S. Merrick

There are no national guidelines when comparing an aspirin daily to a statin drug in individuals with no history of a cardiovascular event (primary prevention). However, recent reviews of the medical clinical research on statins and aspirin for preventing a first coronary heart disease (CHD) event concluded that compared to no treatment, aspirin is cheaper and has more of an impact in middle-aged men whose 10-year risk for CHD is 7.5% or higher, and adding a statin to aspirin therapy is better in terms of cost effectiveness when a patient's 10-year CHD risk before any treatment is greater than 10%. However, when scrutinizing these data it seems that statins beat aspirin in every single risk-reduction category, and has equal to perhaps less side effects, but a statin costs more. In addition, patients should be informed about the recent observational data suggesting that statins may reduce mortality from other causes such as prostate cancer.

Pfizer Inc. recently discontinued its billion-dollar investment and phase III clinical trial of their new high-density lipoprotein (HDL) or "good cholesterol" boosting drug torceptrapib because of unexpected life-threatening side effects. To provide an objective discussion with patients looking for the next miracle drug or even dietary supplement in medicine, it is important to provide an overview of the history of this drug. It should serve as an important lesson that traditional lifestyle factors and proven heart healthy medications have stood the test of time in terms of research. Despite the current interest in drug development, traditional HDL-boosting lifestyle initiatives such as exercise, weight loss, and smoking cessation can be incorporated now and are heart and urologic healthy.

There are a variety of agents, dosages, and mechanisms involved in reducing cholesterol. Statins are the most well-known class and three of the six currently available agents have now lost patent protection. Thus, large reductions in price are expected in 2006-2007 across the entire class. The other classes of cholesterol-lowering agents include targeted triglyceride reducers and high-density lipoprotein boosters; two other classes include primarily cholesterol absorption inhibitors. A recent addition to the cholesterol-lowering prescriptions include prescription omega-3 products, which are highly concentrated, have excellent quality control, and are used to reduce abnormally high levels of triglycerides. All of these agents can be used in some restricted combination, or individually to significantly impact the various forms of lipids in the bloodstream. The bottom line is that practitioners have a large diversity of medications available for cholesterol lowering, and this is enormously exciting at a time when these agents have such profound effects in a variety of disciplines.

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.

We identified clinical, treatment and dosimetric parameters associated with the development of urethral strictures following permanent prostate brachytherapy. From April 1995 through April 2003, 1,186 consecutive patients underwent prostate brachytherapy for clinical stage T1b-T3a NxM0 (2002 American Joint Committee on Cancer) prostate cancer. The treatment plan included supplemental XRT in 625 patients (52.7%) and androgen deprivation therapy in 465 (39.2%). Median followup was 4.3 years. Multiple clinical, treatment and dosimetric parameters were evaluated in univariate and multivariate analyses to identify independent predictors for urethral stricture disease. A total of 29 patients had brachytherapy related urethral strictures. All strictures involved the BM urethra with a 9-year actuarial risk of 3.6% and a median time to development of 2.4 years. The mean radiation dose to the BM urethra was significantly greater in patients with vs without stricture (p = 0.002). On multivariate analysis the BM urethral dose and supplemental XRT predicted urethral stricture. All except 3 patients were successfully treated with urethral dilation or internal optical urethrotomy. Brachytherapy related urethral stricture disease correlates highly with the radiation dose to the BM urethra. Careful attention to brachytherapy preplanning and intraoperative execution along with the judicious use of supplemental XRT is essential to minimize the incidence of stricture disease.

OBJECTIVE: To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0–7), moderate (8–19) and severe (>20) categories, predicts brachytherapy‐related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherapy. PATIENTS AND METHODS: From January 1998 to September 2003, 1034 consecutive patients had permanent interstitial brachytherapy for clinical stage T1b‐T3a NXM0 (2002 system) prostate cancer. Of the 1034 patients, 739 (71.5%) presented with an IPSS of 0–7, 287 (27.7%) of 8–19, and eight (0.8%) of ≥ 20. The IPSS 8–19 cohort was further stratified into 8–14 (237 men) and 15–19 (50 men) subgroups. The median follow‐up was 38.2 months. In all patients, an α‐blocker was initiated before brachytherapy and continued at least until the IPSS normalized, the latter defined as a return to within 1 point of that before implantation. A median of 21 IPSS questionnaires were obtained per patient. Several clinical, treatment and dosimetric variables were evaluated as predictors of urinary morbidity. RESULTS: For the entire cohort, the IPSS peaked at a mean of 0.5 months after implantation and resolved at a mean of 1.7 months. At 5 years after brachytherapy, 90.1% of patients at risk (88.8%, 95.5%, and four of eight patients with a pre‐implant IPSS of 0–7, 8–19 and ≥ 20, respectively) were within the IPSS 0–7 category. Compared to the pre‐implant IPSS, 13 patients (8%) were assigned to a higher IPSS severity category. Neither prolonged urinary catheter dependency (>5 days; 16 patients, 1.5%) or transurethral resection of the prostate (TURP, 17 patients, 1.6%) depended on the pre‐implant IPSS subgroup. In Cox regression analysis, IPSS resolution was best predicted by pre‐implant IPSS, prolonged catheter dependency by patient age, and TURP by any catheter dependency, the maximum IPSS increase and the maximum urethral dose. CONCLUSIONS: The IPSS before implantation predicted the resolution of IPSS after brachytherapy, but did not correlate with substantial urinary morbidity, including catheter dependency or the need for TURP. At 5 years after brachytherapy, 90.1% of patients at risk were assigned to the IPSS 0–7 category.