Sequential androgen blockade: a biological study in the inhibition of prostatic growth.

We attempted to determine the effects of the combination of a 5-alpha reductase inhibitor and an antiandrogen on rat ventral prostate and seminal vesicle weight. We also attempted to determine whether the prostatic cell death gene TRPM-2 would be expressed using this combination of drugs. Adult male Sprague-Dawley rats were randomly assigned to 7 groups of 15 animals. Four groups served as controls: an intact group sacrificed at the initiation of the trial (group 1), a castrate control group (group 2), an intact control group (group 3), and a group treated with the combination of an LHRH agonist plus antiandrogen (group 7). Three other groups were treated with daily subcutaneous injections of 5 alpha reductase inhibitor (group 5), a nonsteroidal pure antiandrogen (group 4) or both (group 6). After 5 days of treatment 5 animals in each group were sacrificed and prostatic tissue was assayed for the androgen repressed prostatic cell death gene TRPM-2. At 30 days (35 days for group 7) the remaining animals were sacrificed and their ventral prostates, seminal vesicles, and testes (except group 3) were weighed. The combination group (group 6) had a significantly lower prostate weight than either of the monotherapy groups (4, 5), or intact control groups, was equivalent to group 7 but was significantly heavier than the castrate group 2. The seminal vesicle weights of the combination group 6 were significantly lower than the monotherapy groups (4, 5), intact control group, castrate group (3) and was equivalent to group 7. Only castration was able to induce expression of the cell death gene TRPM-2. In this model, the combination of 5 alpha reductase inhibitor and an antiandrogen is as effective a mode of androgen ablation as combination therapy of LHRH agonist plus antiandrogen. Clinically, this combination may translate into adequate androgen blockade without impotence or other side effects of testosterone deprivation. Clinical trials appear warranted to assess this hypothesis.     

State-of-the-art hormonal management of prostate cancer

For more than 30 years, maximal androgen blockade has been used in urologic oncology clinical trials practiced with varied degrees of success in the treatment of prostate cancer. While the popularity of maximal androgen blockade has waxed and waned, currently maximal androgen blockade appears to be the optimum treatment for the management of advanced prostate cancer. This opinion paper is intended to review the current approach of maximal androgen blockade and, in particular, address its role in clinical practice. This article reflects the views of 14 urologic experts from Canada, the US and Europe.     

The effect of the chronic administration of a potent luteinizing hormone releasing hormone analog on the rat prostate

In order to assess the effect of the chronic administration of a potent luteinizing hormone releasing hormone analog, (D-SER(But)6) LHRH (1-9) nonapeptide-ethylamide (Buserelin, HOE 766) on the pituitary gonadal axis, and the prostate, adult male Wistar rats were administered either 0, 3, 10 or 50 micrograms./kg. body weight Buserelin subcutaneously daily. At 7, 21, 35 and 42 days of treatment, groups of animals were sacrificed and certain serum endocrine and grave metric parameters determined. In addition, at 1, 21 and 42 days of treatment the 1-hour response of serum LH and serum testosterone to a single injection of 10 micrograms./kg. body weight Buserelin was determined. All treatment doses had similar effects. Serum prolactin and the basal and "acute" response of serum LH to Buserelin (+ delta 5,000 per cent) were unaltered throughout treatment. Testes weight, testicular LH receptor content, and basal and "acute" concentrations of serum testosterone were markedly decreased by 42 days of treatment (48, 89, 88 and 88 per cent, respectively). Although seminal vesicle weight declined 50 per cent at 42 days of treatment, prostate weight was not altered from initial weight, but was significantly lower than age matched control at 42 days of treatment. Buserelin remains a potent stimulator of pituitary LH release even during chronic administration. It markedly reduces serum testosterone through a predominant testicular site of action. Buserelin treatment inhibits the growth of the normal prostate, but does not cause its regression.     

State-of-the-art review on management of end-stage heart failure in amyloidosis: transplant and beyond

Heart Failure Reviews - Cardiac involvement occurs in light-chain (AL), transthyretin wild-type (wtATTR), and hereditary (hATTR) amyloidosis; other types of amyloidosis account...     

High temperature microwave thermotherapy of the prostate

Transurethral microwave thermotherapy of the prostate has been touted as a minimally invasive means of treating symptomatic prostatism. High temperatures (>55 degrees C) appear to yield improved results but require general anesthesia. To determine if high temperature thermotherapy of the prostate was feasible in an outpatient, nonanesthetic setting, we subjected men with symptomatic prostatism secondary to benign prostatic hyperplasia to treatment with a newly developed circumferentially cooled transurethral microwave thermotherapy device, the UroWave. Intraprostatic temperatures were measured on-line and treatment was targeted to achieve temperatures ranging from 45 degrees C-65 degrees C. Fifty-five men with benign prostatic hyperplasia underwent transurethral microwave thermotherapy using the UroWave in an outpatient setting without general anesthesia. Baseline mean peak urinary flow rates were 8.0 cc/sec and mean American Urology Association of the prostate displayed three distinct phases: an initial slow heating phase, a plateau phase of variable duration and a rapid secondary heating phase. The final intraprostatic temperature did not correlate with urethral or rectal temperatures or the amount of power applied. At six months, peak flow increased by 50% and symptoms score declined by 52%. Ninety-four percent of patients had a transurethral resection of the prostate-like defect at cystoscopy with a greater proportion at higher temperatures. Side effects were rare and no patients had to be admitted to hospital. Transurethral microwave thermotherapy at high intraprostatic temperatures can be achieved with general anesthesia. Symptom relief was considerable and anatomic changes resembling a transurethral resection of the prostate were noted in the majority of patients. Intraprostatic temperatures are the only means of assessing the thermal damage to the prostate and thus the effectiveness if therapy. Future studies must develop less invasive means of monitoring intraprostatic temperatures and define the role of the bladder neck. Ultimately, randomized controlled trials will define the value of this treatment.     

Health-related quality of life following radical prostatectomy: long-term outcomes

Purpose

To identify the health-related quality of life (HRQoL) domains that radical prostatectomy (RP) impacts most negatively and to define the recovery of these domains over 30 months of observation.

Patients and methods

A total of 1,200 RP patients completed the Patient-Oriented Prostate Utility Scale-Psychometric (PORPUS-P; range 0–100, higher is better), a prostate cancer-specific HRQoL measure, prior to RP and at 0–3 (T1), 3–9 (T2), 9–18 (T3) and 18–30 (T4) months post-RP. HRQoL changes were examined using paired t tests and a mixed-effect growth curve model. Multivariable analyses were performed to investigate demographic and treatment factors predicting the change in HRQoL.

Results

Mean baseline PORPUS-P score, 83.1, fell to 66.5 (p < 0.001) at T1. Over time HRQoL improved but did not return to baseline (T4 mean 76.4, p < 0.001). Domain analysis revealed that sexual function (p < 0.001), sexual drive (p < 0.001), energy (p = 0.001) and bladder control (p < 0.001) failed to return to baseline at T4. Sexual function demonstrated the greatest impairment overall. The multivariable model revealed Black men experienced greater losses in global HRQoL compared with White men (coefficient ?2.77, 95 % CI ?5.00 to ?0.54, p = 0.015). High baseline HRQoL, pro-erectile aid use and bilateral nerve-sparing were significantly associated with smaller reductions in HRQoL post-RP.

Conclusion

Overall HRQoL, sexual drive, sexual function, energy and bladder control do not return to preoperative levels within 30 months post-RP. Black patients experience the greatest reductions in HRQoL. HRQoL losses may be ameliorated by use of pro-erectile aids. These findings help to identify at-risk patient populations and inform survivorship programs.