Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

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Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

Purpose Androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist is associated with increased fat mass and insulin resistance in men with prostate cancer, but the risk of obesity-related disease during treatment has not been well studied. We assessed whether androgen deprivation therapy is associated with an increased incidence of diabetes and cardiovascular disease. Patients and Methods Observational study of a population-based cohort of 73,196 fee-for-service Medicare enrollees age 66 years or older who were diagnosed with locoregional prostate cancer during 1992 to 1999 and observed through 2001. We used Cox proportional hazards models to assess whether treatment with GnRH agonists or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, and sudden cardiac death. Results More than one third of men received a GnRH agonist during follow-up. GnRH agonist use was associated with increased risk of incident diabetes (adjusted hazard ratio [HR], 1.44...

https://ascopubs.org/doi/pdf/10.1200/JCO.2006.06.2497

Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer

The introduction of an effective blood test, prostate specific antigen (PSA), has made it possible to diagnose more and more men in an earlier stage where they can be offered potentially curative treatments. The other side of the coin is that if effective diagnostic procedures are used unselectively in elderly men with a short life expectancy, a problem with over diagnosis and over treatment might occur. Thus the same stage of prostate cancer may need different treatment strategies, pending on the patient’s life expectancy. This, and many other issues regarding the disease, is the subject of the EAU guidelines on prostate cancer. G UI DE LI N ES O N P RO ST AT E CA N CE R 10

/pdf/guidelines-on-prostate-cancer-xdnunn4th8.pdf

Guidelines on Prostate Cancer

Purpose Androgen suppression therapy (AST) results in musculoskeletal toxicity that reduces physical function and quality of life. This study examined the impact of a combined resistance and aerobic exercise program as a countermeasure to these AST-related toxicities. Patients and Methods Between 2007 and 2008, 57 patients with prostate cancer undergoing AST (commenced > 2 months prior) were randomly assigned to a program of resistance and aerobic exercise (n = 29) or usual care (n = 28) for 12 weeks. Primary end points were whole body and regional lean mass. Secondary end points were muscle strength and function, cardiorespiratory capacity, blood biomarkers, and quality of life. Results Analysis of covariance was used to compare outcomes for groups at 12 weeks adjusted for baseline values and potential confounders. Patients undergoing exercise showed an increase in lean mass compared with usual care (total body, P = .047; upper limb, P < .001; lower limb, P = .019) and similarly better muscle strength (P...

/pdf/combined-resistance-and-aerobic-exercise-program-reverses-3lbju6p4qa.pdf

Combined Resistance and Aerobic Exercise Program Reverses Muscle Loss in Men Undergoing Androgen Suppression Therapy for Prostate Cancer Without Bone Metastases: A Randomized Controlled Trial

Background
Previous studies indicate that androgen deprivation therapy for prostate cancer is associated with diabetes and cardiovascular disease among older men. We evaluated the relationship between androgen deprivation therapy and incident diabetes and cardiovascular disease in men of all ages with prostate cancer.

/pdf/diabetes-and-cardiovascular-disease-during-androgen-1w9guly4ul.pdf

Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy: Observational Study of Veterans With Prostate Cancer

BACKGROUND

The role of androgen deprivation therapy in prostate carcinoma is controversial in earlier stages of disease. The authors examined the time trends and patterns of use for androgen deprivation in the form of gonadotropin-releasing hormone (GnRH) agonists or orchiectomy, in population-based tumor registries.



METHODS

Data were obtained from the linked Surveillance, Epidemiology and End Results-Medicare database. A total of 100,274 men with prostate carcinoma diagnosed from 1991 through 1999 were selected. The main outcome was the proportion of men who received ≥ 1 dose of a GnRH agonist in the first 6 months of diagnosis. This was plotted by year and stratified for age, grade, stage as well as primary versus adjuvant usage. Multiple logistic regression was used to examine predictors of GnRH agonist use in the subset of patients with localized cancer.



RESULTS

There was a consistent increase in GnRH agonist use by year for all ages, stages, and grades. Even in men ≥ 80 years with localized stage and low to moderate grade tumors, primary GnRH agonist use increased over the study period, from 3.7% in 1991 to 30.9% in 1999 (P < 0.001). The multivariable analysis showed that significant variability in GnRH agonist use existed among SEER geographic regions.



CONCLUSIONS

The use of GnRH agonists for prostate carcinoma increased dramatically during the 1990s. This increase occurred across all stages and histologic grades of prostate carcinoma, and was greatest in patients ≥ 80 years. Cancer 2005. © 2005 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20955

Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma

The aim of our study was to systematically determine the effect of Nd:YAG laser in the prostatic tissue of a canine animal model and to define the correlation of laser dose with the depth of coagulation necrosis. This study was carried out with a right angle non contact laser delivery system.

Nd:YAG laser thermal effect in the prostate: application to laser treatment of benign prostatic hyperplasia

We have developed and used a laser optoacoustic imaging system with transrectal probe (LOIS-P) for detection of mechanical lesions in canine prostates in vivo. LOIS images have been acquired with a 128-channel transrectal probe and a 32-channel data acquisition system. Optoacoustic images showed a strong contrast enhancement for a blood containing lesion, when compared with ultrasound images. Our studies demonstrated that sufficient optoacoustic contrast exists between blood containing lesion and prostate tissue, although the lesion has been undetectable with ultrasound. The imaging results have been compared with visual examination of surgically excised prostates. Although axial resolution of the wide-band transducers employed in the transrectal probe provides good axial resolution of 0.5 mm, the convex arc geometry of the this array of transducers provides lateral resolution degrading with depth in tissue. A two step algorithm has been developed to improve the lateral resolution of deeply located objects. This algorithm employs optoacoustic image reconstruction based on radial back-projection to determine location and shape of the target object, then a procedure, we call Maximum Angular Amplitude Probability (MAAP), to determine true brightness of the object and simultaneously remove arc-shaped artifacts associated with radial back-projection. A laser optoacoustic imaging system (LOIS-P) with transrectal probe operating in backward detection mode empowered with the new image reconstruction algorithm seems promising as a modality for detection of prostate cancer and guiding prostate biopsy.

In vivo testing of laser optoacoustic system for image-guided biopsy of prostate

This paper examines the potential effectiveness of a high power, 810 nm diode laser in inducing thermal coagulation of prostatic tissue. A theoretical study is performed to compare the effectiveness of the diode laser with the currently used Nd:YAG laser (1064 nm) for prostate coagulation. Transurethral diode laser irradiation in a canine model is also performed to examine the efficacy of inducing thermal coagulation in vivo. Model results show that comparable tissue effects can be obtained with both diode and Nd:YAG lasers. The in vivo results indicate that considerable amount of coagulation necrosis of prostatic tissue can be induced by the high power diode laser.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Application of a high-power diode laser (810 nm) for treatment of benign prostatic hyperplasia: theoretical and experimental analysis

The objective of the study was to compare the extent of thermocoagulation induced in the human prostate by two regimens of Nd:YAG laser (50 W X 60 s and 15 W X 180 s) and one regimen of diode (810 nm) laser (15 W X 180 s). Powers were measured at the fiber tip. The study was conducted in 6 patients undergoing radical prostatectomy because of malignancy whose prostates were treated transurethrally with laser radiation at the time of the procedure. The prostate specimens were retrieved approximately 90 minutes after laser treatment, and then prepared for histological examination. In all the cases, the diode laser was applied to the left side of the prostate and the Nd:YAG laser (either regimen) to the right side, in order to prevent treatment variables related to histological composition. Coagulation necrosis was confined within the transition zone in all the case and at times BPH was unaffected, if nodular. Similar depth of coagulation was observed for both Nd:YAG regimens (mean 12 mm, range 10 to 14) and the depth of coagulation was slightly less for the diode laser (mean 10.6 mm, range 8 to 14). Our results suggest that, at the studied dosimetries, the thermocoagulation effect of diode laser in the human prostate approximates to that seen with Nd:YAG laser.

Comparison of the extent of Nd:YAG and diode (810 nm) laser-induced thermal coagulation of human prostate: a histopathological analysis of acute response

Eduardo Orihuela

Papers

Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma

Nd:YAG laser thermal effect in the prostate: application to laser treatment of benign prostatic hyperplasia

In vivo testing of laser optoacoustic system for image-guided biopsy of prostate

Application of a high-power diode laser (810 nm) for treatment of benign prostatic hyperplasia: theoretical and experimental analysis

Comparison of the extent of Nd:YAG and diode (810 nm) laser-induced thermal coagulation of human prostate: a histopathological analysis of acute response