Prostate ...

[Michael Scally MD]

Abbott Receives FDA Approval for a New Six-Month Formulation of Lupron Depot® (leuprolide acetate for depot suspension) for the Palliative Treatment of Advanced Prostate Cancer
New six-month formulation expands Lupron Depot dosing options, which currently include one-month, three-month and four-month formulations
http://finance.yahoo.com/news/Abbott-Receives-FDA-Approval-prnews-722447275.html

ABBOTT PARK, Ill., June 20, 2011 /PRNewswire/ -- Abbott announced today that the U.S. Food and Drug Administration (FDA) has approved a new 45 mg for six-month administration formulation of Lupron Depot® (leuprolide acetate for depot suspension), a medication used for the palliative treatment of advanced prostate cancer.

 

[BBC3]

Doc, I recently heard gossip that there is some new documentation out there via new studies that are indicating that Prostate Cancer may now be proven to be increased or made worse by the application of drugs like Finastaride and the like. Can you confirm or deny this.? I think the context was when they are used to treat BPH is where it is stemming from?

 

[HeadDoc]

Human vaccine used to cure prostate cancer in mice

Xinhua News Agency - CEIS

06-20-11

Human vaccine used to cure prostate cancer in mice

LOS ANGELES, June 19 (Xinhua) -- U.S. researchers, in cooperation with their British counterparts, have succeeded in applying human vaccine to curing prostate cancer in mice with no apparent side effects.

"We are hopeful that this will overcome some of the major hurdles which we have seen with immunotherapy cancer research," says Richard Vile, Ph.D., an immunologist at Mayo Clinic in Rochester, Minnesota, lead author of the study. Vile is also a professor at Richard M. Schulze Family Foundation.

The findings appear in the June issue of the journal Nature Medicine.

The hunt for effective cancer treatment vaccines has been going on for decades with varying degrees of success early on, but the new prostate cancer vaccine takes a markedly different approach.

Instead of aiming at a few cancer-causing proteins or antigens on the tumor, the new vaccine casts a much wider net. The goal of a cancer vaccine is to trick the body's immune system into recognizing the tumor as an invader and attacking it. This is typically done using a virus as a host.

To develop this new approach, geneticists assembled snippets of genetic code from healthy human prostate tissue into a complementary DNA (cDNA) library. These bits of cDNA were then inserted into a swarm of vesicular stomatitis viruses (VSV), which were cultured and reintroduced into the test mice as a vaccine during a series of intravenous injections.

The use of viruses as vectors for cDNA libraries overcomes the difficulty of isolating antigens in tumor cells by giving the immune system a more complete picture of the cancerous invader.

This novel cancer treatment approach encourages the immune system to rid itself of prostate tumors without assistance from toxic chemotherapies and radiation treatments. Such a treatment model could some day help people to live tumor free with fewer side effects than those experienced from current therapies, the researchers say.

But the researchers caution that the research is still in its infancy and has yet to be tested in humans. Clinical trials could begin within two years.

(c) 2011 Xinhua News Agency - CEIS. Provided by ProQuest LLC. All rights Reserved.

Copyright Xinhua News Agency - CEIS 2011

 

[Michael Scally MD]

Human vaccine used to cure prostate cancer in mice

Xinhua News Agency - CEIS

06-20-11

Human vaccine used to cure prostate cancer in mice

LOS ANGELES, June 19 (Xinhua) -- U.S. researchers, in cooperation with their British counterparts, have succeeded in applying human vaccine to curing prostate cancer in mice with no apparent side effects.

"We are hopeful that this will overcome some of the major hurdles which we have seen with immunotherapy cancer research," says Richard Vile, Ph.D., an immunologist at Mayo Clinic in Rochester, Minnesota, lead author of the study. Vile is also a professor at Richard M. Schulze Family Foundation.

The findings appear in the June issue of the journal Nature Medicine.

Kottke T, Errington F, Pulido J, et al. Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nat Med;advance online publication. Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors : Nature Medicine : Nature Publishing Group

Effective cancer immunotherapy requires the release of a broad spectrum of tumor antigens in the context of potent immune activation. We show here that a cDNA library of normal tissue, expressed from a highly immunogenic viral platform, cures established tumors of the same histological type from which the cDNA library was derived. Immune escape occurred with suboptimal vaccination, but tumor cells that escaped the immune pressure were readily treated by second-line virus-based immunotherapy. This approach has several major advantages. Use of the cDNA library leads to presentation of a broad repertoire of (undefined) tumor-associated antigens, which reduces emergence of treatment-resistant variants and also permits rational, combined-modality approaches in the clinic. Finally, the viral vectors can be delivered systemically, without the need for tumor targeting, and are amenable to clinical-grade production. Therefore, virus-expressed cDNA libraries represent a novel paradigm for cancer treatment addressing many of the key issues that have undermined the efficacy of immuno- and virotherapy to date.

 

[Michael Scally MD]

[The bottom line: SMOKING IS BAD.]

Smoking and Prostate Cancer Survival and Recurrence

Accumulating evidence suggests that smoking may increase risk of aggressive prostate cancer and prostate cancer mortality. The latest review by the US surgeon general found the evidence “probable” that smoking contributes to a higher prostate cancer mortality rate, in agreement with a review of the literature in which researchers reported an approximately 30% increase in risk of fatal prostate cancer when comparing current with never smokers. Several studies reported that smoking is associated with more aggressive disease at diagnosis, defined as a higher stage or tumor grade and the relation between smoking and disease progression after diagnosis, defined as biochemical recurrence, metastasis, and hormone-refractory prostate cancer, is suggestively positive.

However, these studies had few prostate cancer–specific deaths and either observed no clear association with prostate cancer mortality or did not examine this outcome. Three studies reported a positive association between smoking and prostate cancer mortality but were based on 57 and 54 prostate cancer death or an unspecified number of deaths in a single-institution study of 214 patients. Moreover, concern remains that some or all of the observed associations may be due to delayed diagnosis and treatment among smokers.

With 8 years of follow-up in the Health Professionals Follow-Up Study, researchers previously provided preliminary data on smoking status in relation to prostate cancer mortality. With 22 years of follow-up and a large number of outcomes, they now can examine in detail the relation of current and former smoking to overall and prostate cancer–specific mortality and recurrence in a nationwide cohort of prostate cancer patients.

They observed an elevated risk of prostate cancer mortality, CVD mortality, total mortality, and biochemical recurrence among men who were current smokers at the time of their prostate cancer diagnosis. Former smokers who had quit 10 or more years prior to diagnosis had risks for prostate cancer mortality and recurrence similar to those who had never smoked. Those who had quit for less than 10 years prior to diagnosis and with less than 20 pack-years had risks similar to current smokers for prostate cancer recurrence (an early progression event) but similar to never smokers for prostate cancer mortality.

In their assessment of the impact of smoking beyond its effect on stage and grade, which they considered intermediates of the relation between smoking and biochemical recurrence and prostate cancer–specific mortality, these associations remained elevated but were attenuated, as expected, providing evidence that the effect of smoking is mediated by these factors. Nevertheless, even after adjustment for stage and grade, the estimate for biochemical recurrence remained significant.


Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and Prostate Cancer Survival and Recurrence. JAMA: The Journal of the American Medical Association 2011;305(24):2548-55. Smoking and Prostate Cancer Survival and Recurrence, June 22/29, 2011, Kenfield et al. 305 (24): 2548 — JAMA

Context Studies of smoking in relation to prostate cancer mortality or recurrence in prostate cancer patients are limited, with few prostate cancer–specific outcomes.

Objective To assess the relation of cigarette smoking and smoking cessation with overall, prostate cancer–specific, and cardiovascular disease (CVD) mortality and biochemical recurrence among men with prostate cancer.

Design, Setting, and Participants Prospective observational study of 5366 men diagnosed with prostate cancer between 1986 and 2006 in the Health Professionals Follow-Up Study.

Main Outcome Measures Hazard ratios (HRs) for overall, prostate cancer–specific, and CVD mortality, and biochemical recurrence, defined by an increase in prostate-specific antigen (PSA) levels.

Results There were 1630 deaths, 524 (32%) due to prostate cancer and 416 (26%) to CVD, and 878 biochemical recurrences. Absolute crude rates for prostate cancer–specific death for never vs current smokers were 9.6 vs 15.3 per 1000 person-years; for all-cause mortality, the corresponding rates were 27.3 and 53.0 per 1000 person-years. In multivariable analysis, current vs never smokers had an increased risk of prostate cancer mortality (HR, 1.61; 95% confidence interval [CI], 1.11-2.32), as did current smokers with clinical stage T1 through T3 (HR, 1.80; 95% CI, 1.04-3.12). Current smokers also had increased risk of biochemical recurrence (HR, 1.61; 95% CI, 1.16-2.22), total mortality (HR, 2.28; 95% CI, 1.87-2.80), and CVD mortality (HR, 2.13; 95% CI, 1.39-3.26). After adjusting for clinical stage and grade (likely intermediates of the relation of smoking with prostate cancer recurrence and survival), current smokers had increased risk of prostate cancer mortality (HR, 1.38; 95% CI, 0.94-2.03), as did current smokers with clinical stage T1 through T3 (HR, 1.41; 95% CI, 0.80-2.49); they also had an increased risk of biochemical recurrence (HR, 1.47; 95% CI, 1.06-2.04). Greater number of pack-years was associated with significantly increased risk of prostate cancer mortality but not biochemical recurrence. Current smokers of 40 or more pack-years vs never smokers had increased prostate cancer mortality (HR, 1.82; 95% CI, 1.03-3.20) and biochemical recurrence (HR, 1.48; 95% CI, 0.88-2.48). Compared with current smokers, those who had quit smoking for 10 or more years (HR, 0.60; 95% CI, 0.42-0.87) or who have quit for less than 10 years but smoked less than 20 pack-years (HR, 0.64; 95% CI, 0.28-1.45) had prostate cancer mortality risks similar to never smokers (HR, 0.61; 95% CI, 0.42-0.88).

Conclusions Smoking at the time of prostate cancer diagnosis is associated with increased overall and CVD mortality and prostate cancer–specific mortality and recurrence. Men who have quit for at least 10 years have prostate cancer–specific mortality risks similar to those who have never smoked.

 

[Michael Scally MD]

Bioactivation Of Androstanediol By Conversion To Dihydrotestosterone

Recent studies highlight the potential importance of intratumoral androgen biosynthesis in prostate cancer. Mass spectrometry measurements of Castrate Resistant Prostate Cancer (CRPC) tissue extracts indicate sufficient Dihydrotestosterone (DHT) to activate Androgen Receptor (AR). In agreement with these findings, finasteride, a 5?-reductase type 2 inhibitor, or dutasteride, a dual 5?-reductase types 1 and 2 inhibitor, were ineffective in preventing prostate cancer development or in treating aggressive prostate cancer.

One interpretation of these clinical studies is that alternative androgen biosynthetic pathways provide sufficient DHT to activate AR in the abnormal cellular environment of prostate cancer. CRPC is characterized by increased expression of coactivators and coregulators that enhance AR sensitivity to low-level androgens. These findings suggest that highly plastic prostate cancer cells utilize alternative mechanisms to eventually escape drug treatments that target AR.


Mohler JL, Titus MA, Wilson EM. Potential prostate cancer drug target: Bioactivation of androstanediol by conversion to dihydrotestosterone. Clin Cancer Res. Potential prostate cancer drug target: Bioactivati... [Clin Cancer Res. 2011] - PubMed result

High affinity binding of dihydrotestosterone (DHT) to the androgen receptor (AR) initiates androgen-dependent gene activation required for normal male sex development in utero, and contributes to prostate cancer development and progression in men. Under normal physiological conditions, DHT is synthesized predominantly by 5alpha-reduction of testosterone, the major circulating androgen produced by the testis. During androgen deprivation therapy, intratumoral androgen production is sufficient for AR activation and prostate cancer growth even though circulating testicular androgen levels are low. Recent studies indicate that the metabolism of 5alpha-androstane-3alpha,17beta-diol by 17beta-hydroxysteroid dehydrogenase 6 in benign prostate and prostate cancer cells is a major biosynthetic pathway for intratumoral synthesis of DHT that binds AR and initiates transactivation to promote prostate cancer growth during androgen deprivation therapy.

Drugs that target the so-called backdoor pathway of DHT synthesis provide an opportunity to enhance clinical response to LHRH agonists or antagonists, AR antagonists, inhibitors of 5alpha-reductase enzymes, finasteride or dutasteride, and steroid metabolism enzyme inhibitors, ketoconazole or the recently available abiraterone acetate.

 

[Michael Scally MD]

Targeting 5[Alpha]-Reductase For Prostate Cancer

This review will summarize the current knowledge of the role of testosterone and dihydrotestosterone (DHT) in prostate disease and discuss the rationale for using treatments that target the synthesis of DHT in the treatment of prostate cancer. They will also bring together the data from the two largest trials of 5?-reductase inhibitors (5ARIs) in prostate cancer, and consider the future of these drugs in clinical practice.

Nacusi LP, Tindall DJ. Targeting 5[alpha]-reductase for prostate cancer prevention and treatment. Nat Rev Urol 2011;8(7):378-84. Targeting 5[alpha]-reductase for prostate cancer prevention and treatment : Abstract : Nature Reviews Urology

Testosterone is the most abundant circulating androgen, and can be converted to dihydrotestosterone (DHT), a more potent androgen, by the 5?-reductase enzymes in target tissues. Current treatments for prostate cancer consist of reducing androgen levels by chemical or surgical castration or pure antiandrogen therapy that directly targets the androgen receptor (AR). Although these therapies reduce tumor burden and AR activity, the cancer inevitably recurs within 18–30 months. An approach targeting the androgen–AR axis at different levels could, therefore, improve the efficacy of prostate cancer therapy. Inhibition of 5?-reductase is one such approach; however, the two largest trials to investigate the use of the 5?-reductase inhibitors (5ARIs) finasteride and dutasteride in patients with prostate cancer have shown that, although the incidence of cancer was reduced by 5ARI treatment, those cancers that were detected were more aggressive than in patients treated with placebo. Thus, the best practice for using these drugs to prevent and treat prostate cancer remains unclear.

 

[BBC3]

Good one!!!

I would like to interject to possible premise that much of the context we study prostate cancer in is under the premise of cancer already existing. Meaning, while its all very productive, the industry still seems to misdirect the focus of the profile of conditions to CAUSE the cancer. ANY hormone profile the would be considered "normal", I am guessing is going to only feed the cancer fire once started. So the point is (and there are different kinds of PC which have to be qualified), it is possible that high androgen activity in the prostate may not even be condusive to PC with other variable profiles accounted. But once the cancer is set up, Androgens can be the end in a hurry. This is a FAILURE in current medical science to which has skewed the thinking so wrong for so many years, thus pointing what may have been a false finger at androgens, perhaps....

Targeting 5[Alpha]-Reductase For Prostate Cancer

This review will summarize the current knowledge of the role of testosterone and dihydrotestosterone (DHT) in prostate disease and discuss the rationale for using treatments that target the synthesis of DHT in the treatment of prostate cancer. They will also bring together the data from the two largest trials of 5?-reductase inhibitors (5ARIs) in prostate cancer, and consider the future of these drugs in clinical practice.

Nacusi LP, Tindall DJ. Targeting 5[alpha]-reductase for prostate cancer prevention and treatment. Nat Rev Urol 2011;8(7):378-84. Targeting 5[alpha]-reductase for prostate cancer prevention and treatment : Abstract : Nature Reviews Urology

Testosterone is the most abundant circulating androgen, and can be converted to dihydrotestosterone (DHT), a more potent androgen, by the 5?-reductase enzymes in target tissues. Current treatments for prostate cancer consist of reducing androgen levels by chemical or surgical castration or pure antiandrogen therapy that directly targets the androgen receptor (AR). Although these therapies reduce tumor burden and AR activity, the cancer inevitably recurs within 18–30 months. An approach targeting the androgen–AR axis at different levels could, therefore, improve the efficacy of prostate cancer therapy. Inhibition of 5?-reductase is one such approach; however, the two largest trials to investigate the use of the 5?-reductase inhibitors (5ARIs) finasteride and dutasteride in patients with prostate cancer have shown that, although the incidence of cancer was reduced by 5ARI treatment, those cancers that were detected were more aggressive than in patients treated with placebo. Thus, the best practice for using these drugs to prevent and treat prostate cancer remains unclear.

 

[Michael Scally MD]

Old Gene Fusion - New Diagnostic Tricks

The ''PSA test'' is a routine test for men over the age of 50 or for those at risk for prostate cancer. It measures the level of prostate-specific antigen (PSA) in the blood, and if that level is above a predefined cutoff, a biopsy is recommended for definitive diagnosis. This test is not perfect; benign conditions, such as an enlarged prostate, can contribute to high levels of PSA, resulting in a ''false-positive'' and subsequent overdiagnosis and overtreatment. Because of the high prevalence of prostate cancer (it is estimated that nearly 250,000 men will be diagnosed with the disease in 2011), it is clear that a more accurate test for prostate cancer is needed.

Here, Tomlins et al. improve on the PSA test by taking a new twist on a known gene fusion, using it to stratify more than 1000 men in two multicenter cohorts based on risk for developing the disease. Recently, it was discovered that the fusion of two genes, the transmembrane protease, serine 2 (TMPRSS2) gene and the v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene, known as TMPRSS2:ERG, is overexpressed in more than 50% of PSA-screened prostate cancers.

The protein product of this fusion cannot be detected in serum, so the authors decided to test for the presence of TMPRSS2:ERG mRNA in urine. First, they developed a clinical-grade, transcription-mediated amplification assay for quantifying fusion mRNA--this generated a TMPRSS2:ERG ''score.'' Urine TMPRSS2:ERG score was linked to the presence of cancer, tumor volume, and clinically significant cancer in patients.

Then, the authors combined the TMPRSS2:ERG score with the level of prostate cancer antigen 3 (PCA3) in urine. TMPRSS2:ERG+PCA3 improved the performance of the multivariate Prostate Cancer Prevention Trial risk calculator, thus demonstrating clinical utility.

Who said you can't teach an old gene fusion new tricks? By combining the cancer-specific fusion TMPRSS2:ERG score with levels of PSA (in serum) and PCA3 (in urine), Tomlins and colleagues demonstrated more accurate, individualized stratification of men at high risk for developing clinically significant prostate cancer--an important step in streamlining diagnosis and treatment. Moreover, men with extremes of TMPRSS2:ERG+PCA3 had different risks of cancer on biopsy; in combination with other clinicopathological features, urine TMPRSS2:ERG+PCA3 might also inform the urgency of biopsy after PSA screening.


Tomlins SA, Aubin SMJ, Siddiqui J, et al. Urine TMPRSS2:ERG Fusion Transcript Stratifies Prostate Cancer Risk in Men with Elevated Serum PSA. Science Translational Medicine 2011;3(94):94ra72. Urine TMPRSS2:ERG Fusion Transcript Stratifies Prostate Cancer Risk in Men with Elevated Serum PSA

More than 1,000,000 men undergo prostate biopsy each year in the United States, most for “elevated” serum prostate-specific antigen (PSA). Given the lack of specificity and unclear mortality benefit of PSA testing, methods to individualize management of elevated PSA are needed. Greater than 50% of PSA-screened prostate cancers harbor fusions between the transmembrane protease, serine 2 (TMPRSS2) and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) genes. Here, we report a clinical-grade, transcription-mediated amplification assay to risk stratify and detect prostate cancer noninvasively in urine. The TMPRSS2:ERG fusion transcript was quantitatively measured in prospectively collected whole urine from 1312 men at multiple centers. Urine TMPRSS2:ERG was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size, high Gleason score at prostatectomy, and upgrading of Gleason grade at prostatectomy. TMPRSS2:ERG, in combination with urine prostate cancer antigen 3 (PCA3), improved the performance of the multivariate Prostate Cancer Prevention Trial risk calculator in predicting cancer on biopsy. In the biopsy cohorts, men in the highest and lowest of three TMPRSS2:ERG+PCA3 score groups had markedly different rates of cancer, clinically significant cancer by Epstein criteria, and high-grade cancer on biopsy. Our results demonstrate that urine TMPRSS2:ERG, in combination with urine PCA3, enhances the utility of serum PSA for predicting prostate cancer risk and clinically relevant cancer on biopsy.

 

[Michael Scally MD]

The Phytoestrogen Genistein Is a Tissue Specific Androgen Receptor Modulator

Prostate cancer is one of the most common malignancies among men in developed countries and an important cause of cancer deaths. Prostate growth is promoted throughout life by androgens, the male sex hormones, that also play a role in the development of prostatic tumors. In recent years, results from epidemiological studies have indicated that some dietary factors that modulate sex hormone signaling are also associated with an increased or decreased risk of prostate cancer.

The incidence of prostate cancer varies between populations worldwide, being over 400-fold higher in Westerns countries than in Asia. One contributing factor for the differences in incidence could be lifestyle, especially the diet. This notion is supported by epidemiological studies and by comparative research on immigrants moving from Asia to the United States, whose prostate cancer risk becomes similar to that of the North American population.

One food item that is consumed more in Asia than in Western societies is soy, which contains two predominant polyphenolic isoflavones, genistein and daidzein. Genistin is a biologically inactive glycosylated form of genistein, and hydrolysis of genistin in the intestine results in bioactive genistein aglycone. Isoflavones are phytoestrogenic compounds that share structural similarity with estradiol and are known to exhibit estrogenic effects in cells. Frequent consumption of soy products has been associated with reduction of prostate cancer risk in several cohort and case-controlled studies.

Genistein is a widely studied compound in cancer prevention. Its structural similarity to steroid hormones and low incidence of hormonal cancers in soy-consuming Asian countries make genistein a potential candidate for a cancer-inhibiting compound. Dietary genistein has been reported to inhibit prostate cancer metastasis and life-long exposure to dietary genistein to attenuate development and progression of prostate cancer in the transgenic adenocarcinoma of the mouse prostate mouse model. The researchers findings support genistein’s potential role in prostate cancer prevention, and they conclude that it affects AR-mediated gene expression in vivo in a tissue-specific and context-dependent fashion at a concentration relevant to human exposure on a soy-rich diet.


Pihlajamaa Pi, Zhang F-P, Saarinen L, Mikkonen L, Hautaniemi S, Janne OA. The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator. Endocrinology. The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator

To enable studies of androgen signaling in different tissues in vivo, we generated an androgen receptor (AR) reporter mouse line by inserting a luciferase gene construct into the murine genome. The construct is driven by four copies of androgen-responsive elements from the mousesex-limited protein gene (slp-HRE2) and a minimal thymidine kinase promoter. Luciferase activity was readily measurable in a number of murine tissues, including prostate, lung, testis, brain, and skeletal muscle, and testosterone administration elicited a significant increase in reporter gene activity in these tissues. Consumption of isoflavonoid genistein is linked to reduced risk of prostate cancer, but direct effects of genistein on the AR pathway are not well understood. To examine androgen-modulating activity of genistein in vivo, male mice received daily doses of genistein (10 mg/kg) for 5 d. In intact males, genistein was antiandrogenic in testis, prostate, and brain, and it attenuated reporter gene activity by 50–80%. In castrated males, genistein exhibited significant androgen agonistic activity in prostate and brain by increasing reporter gene activity over 2-fold in both tissues. No antiandrogenic action was seen in lung or skeletal muscle of intact males. Gene expression profiling of the murine prostate under the same experimental conditions revealed that genistein modulates androgen-dependent transcription program in prostate in a fashion similar to that observed in reporter mice by luciferase expression. In conclusion, genistein is a partial androgen agonist/antagonist in some but not in all mouse tissues and should be considered as a tissue-specific AR modulator.

 

[BBC3]

I would like to interject a GROUND POINT for those following at this time. Obviosly, the mainstream notion of days past has been that DHT/Androgens lead to and/or contribute to the DEVELOPMENT of Prostate Cancer. All the new information (Finally Comming) is hinting toward the possibility a estrogens as a PRIMARY CULPRET in THE DEVELOPMENT of prostate cancer. I DO notably underline DEVELOPMENT. The reason for this is that the OBVIOUS FAILURE of Major Medical as a business$$ is that they only focus on treating a disease, NOT PREVENTING ONE. Of COURSE androgens and DHT will Fuel a Cancer fire in the prostate - ONCE STARTED. The question remains - WHAT CAUSED IT.??? Estrogens in high proportion are NOT NORMAL in males. Estrogens I think are even documented to metabolize into a CARCINAGEN at the level of E3 and beyond. While estrogens are required in many essential processes in all males to SOME Degree, again moderation prevails. So I am have family history of PC and it appears to relate to estrogens primarily. I am of the opinion there Estrogens are a primary culpret and I am watching.

 

[BBC3]

Doc, I am wondering if there is any data out there gathered that demonstrates the corrolation of (3) factors. Age, Body Fat, and Physical Activity levels. Could it be as simple as being fat, not being fat but having poor androgen metabolism profile, could corrolate directly with the incidence of PC as individuals age. And with condieration of GENETIC PROPENSITY....?

Nahh. That would be too OBVIOUS, LOL. It would also present as Too definitive and folks might actually listen and behave accordingly. Finally, it might just mess up the ever critical mortality rate with regard to MANY ILLNESSES and force society to increase the current LOGANS RUN F.D.A. Phylosophy in place...

Dont tell me an old guy with PC is not fat!!!!! Dont tell me a young, skinny guy with PC is Not sedentary, or lacking in adrogen activity. Dont tell me there is any "mystery to it". Society is pathetically lazy inclusive of MYSELF!!!!

 

[Michael Scally MD]

Prediction of Erectile Function Following Treatment for Prostate Cancer

Because most patients survive early-stage prostate cancer after treatment, health-related quality of life (HRQOL) outcomes have emerged as a major emphasis in treatment decisions. Erectile dysfunction is commonplace after prostate cancer treatment and has significant consequences for HRQOL. Among urinary, bowel, vitality, and sexual HRQOL domains—outcomes commonly impaired by prostate cancer treatment—sexual function in previously potent men is the most commonly impaired and is closely related to outcome satisfaction.

Individual characteristics, such as pretreatment erectile function, that influence post treatment sexual outcome are known to vary at diagnosis, yet tools to predict post treatment erectile dysfunction based on pretreatment sexual HRQOL at baseline have been limited. Treatment refinements, such as nerve-sparing techniques, can mitigate erectile dysfunction consequences of prostate cancer treatment, while other treatment variations, such as use of neoadjuvant hormone therapy, can adversely affect sexual outcome. Although associations of these and other factors with patient-reported sexual outcome have been studied, information regarding how the combination of pretreatment patient characteristics and treatment factors relate to individualized sexual outcome remains limited.

Researchers sought to determine whether an individual man's sexual outcomes after the most common treatments for early-stage prostate cancer (radical prostatectomy, external radiotherapy, or brachytherapy) can be predicted accurately based on baseline characteristics and treatment planning details. The ability to inform individual patients how likely they are to develop erectile dysfunction based on their personal baseline sexual function, cancer severity, individual clinical characteristics, and treatment plan has been elusive. Their findings address this need by providing a validated, broadly applicable framework to predict the probability of long-term, post treatment erectile dysfunction for individual patients.


Alemozaffar M, Regan MM, Cooperberg MR, et al. Prediction of Erectile Function Following Treatment for Prostate Cancer. JAMA: The Journal of the American Medical Association 2011;306(11):1205-14. Prediction of Erectile Function Following Treatment for Prostate Cancer, September 21, 2011, Alemozaffar et al. 306 (11): 1205 — JAMA

Context Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking.

Objective To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics.

Design Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years' follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort.

Main Outcome Measures Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment.

Results Two years after prostate cancer treatment, 368 (37% [95% CI, 34%-40%]) of all patients and 335 (48% [95% CI, 45%-52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%-56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual's pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74-0.80] for prostatectomy; 0.87 [95% CI, 0.80-0.94] for external radiotherapy; and 0.90 [95% CI, 0.85-0.95] for brachytherapy).

Conclusion Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer.

 

[Michael Scally MD]

Bayer Presents Full Dataset for Alpharadin in CRPC
http://finance.yahoo.com/news/Positive-Phase-III-Data-on-prnews-1782800329.html?x=0&.v=1

Friday September 23, 2011, 6:01 pm EDT

WAYNE, N.J., Sept. 23, 2011 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals today announced that the investigational drug radium-223 chloride showed positive data in the Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. The study met its primary endpoint by significantly improving overall survival by 44% (p=0.00185, HR=0.695) in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. All of the main secondary efficacy endpoints analyzed to date were met, including delay in skeletal-related events (SREs). These data will be presented during the Presidential Session at the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden (Abstract No. 1LBA: Presidential Session I: Best and Late Breaking Abstracts, Saturday, September 24, 13.45 (CEST), Hall A1). The 2011 European Multidisciplinary Cancer Congress is the 16th congress of the European CanCer Organisation (ECCO), the 36th congress of the European Society for Medical Oncology (ESMO) and the 30th congress of the European Society for Therapeutic Radiology and Oncology (ESTRO).

The data showed that patients who were treated with radium-223 chloride had the following outcomes:

• Median overall survival of 14 months compared to 11.2 months for the placebo group,

• Time to first SREs (13.6 months vs. 8.4 months, 64% improvement, HR=0.610, p=0.00046),

• Total alkaline phosphatase (ALP) normalization (33% vs. 1% of patients, p<0.001); and

• A 49% improvement in time to prostate-specific antigen (PSA) progression (HR=0.671, p=0.00015).

The most common non-hematologic adverse events (occurring in at least 15% of patients) included bone pain (43% vs. 58%), nausea (34% vs. 32%), diarrhea (22% vs. 13%), constipation (18% vs. 18%) and vomiting (17% vs. 13%); and the most common hematologic adverse events included anemia (27% vs. 27%) for patients receiving radium-223 chloride as compared to placebo. With respect to Grade 3 to 4 adverse events, the most common events included bone pain (18% vs. 23%) for patients receiving radium-223 chloride as compared to placebo. [As previously reported] following a pre-planned interim analysis, the company agreed with the Independent Data Monitoring Committee's (IDMC) recommendation to stop the study and offer patients on the placebo arm treatment with radium-223 chloride.

"Radium-223 chloride is the first bone-targeted, alpha-emitting, radiopharmaceutical to demonstrate a survival benefit in men with castration-resistant prostate cancer and symptomatic bone metastases," said Dr. Oliver Sartor of Tulane Medical School, New Orleans, and an ALSYMPCA trial investigator.

Radium-223 chloride was recently granted Fast Track designation by the U.S. Food and Drug Administration (FDA). The Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The company plans to file a New Drug Application with the FDA for radium-223 chloride in mid-2012.

ALSYMPCA Trial Design

The ALSYMPCA trial is a Phase III, randomized (2:1), double-blind, placebo-controlled international study of radium-223 chloride plus current standard of care compared with placebo plus current standard of care in patients with symptomatic CRPC that has spread to the bone. The primary endpoint of the study is overall survival. Secondary endpoints include time to occurrence of SREs, changes and time to progression in PSA and ALP, safety, and impact on quality of life measures.

ALSYMPCA enrolled 922 patients in more than 100 centers in 19 countries who have histologically or cytologically confirmed adenocarcinoma of the prostate, known hormone refractory disease, multiple skeletal metastases (greater than or equal to 2 hot spots) on bone scintigraphy, no intention to use cytotoxic chemotherapy within the next 6 months and either regular (not occasional) analgesic medication use for cancer-related bone pain or treatment with EBRT for bone pain. ALSYMPCA was initiated by Algeta ASA (Oslo, Norway) in June 2008.

About Radium-223 Chloride

Radium-223 chloride is an investigational alpha-pharmaceutical (an alpha-emitting radiopharmaceutical) in development for cancer patients with bone metastases. In September 2009, Bayer signed an agreement with Algeta for the development and commercialization of radium-223 chloride. Under the terms of the agreement, Bayer will develop, apply for global health authority approvals, and commercialize radium-223 chloride globally, while Algeta retains an option for up to 50/50 co-promotion and profit-sharing in the United States.

 

[Michael Scally MD]

[This IS NOT a typo! The research calls for testosterone use in PrCa. Moreover, at levels of 2500-3500 ng/dL, which is north of 200 mg/week.]

Androgens As Therapy For Androgen Receptor Positive Castration Resistant Prostate Cancer

Based on the results from the researchers’ model, patients developing relapsed hormone-refractory prostate tumors after androgen ablation therapy should be biopsied for expression level of Androgen Receptor (AR) protein in tumors. Intermittent Androgen Deprivation (IAD) and/or administration of exogenous androgen at a concentration 2500-3500 ng/dl will benefit patients with AR-rich relapsed tumors by suppressing tumor growth, improving quality of life, and reducing risks for cardiovascular diseases and diabetes. Combined treatment of androgen ablation therapy with anti-androgen causes a rapid and irreversible selection of more aggressive advanced prostate cancer cells. Exogenous androgen treatment can cause regression of these tumors and a subgroup of these tumors will disappear.

Androgen deprivation therapy alone may promote a slow adaptation to androgen ablation-resistance, thus shortening the period of androgen deprivation therapy may retard the diseases progression and reduce side effects. Aromatase inhibitors should be considered in combination with androgen treatment to prevent the conversion of testosterone to estradiol (E2) by aromatase to avoid potential cardiac toxicity. Since several clinical trials already confirmed that testosterone is a safe, feasible, and reasonably well-tolerated therapy for men with early hormone-refractory prostate cancer, we believe that manipulating androgen/AR signaling can be a potential therapy for AR-positive advanced prostate cancer.


Chuu CP, Kokontis JM, Hiipakka RA, et al. Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer. J Biomed Sci 2011;18:63. Journal of Biomedical Science | Full text | Androgens as Therapy for Androgen Receptor-Positive Castration-Resistant Prostate Cancer

Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in Western countries. While surgery is often successful for organ-confined prostate cancer, androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. Shortening the period of androgen ablation therapy may benefit prostate cancer patients. Intermittent Androgen Deprivation therapy improves quality of life, reduces toxicity and medical costs, and delays disease progression in some patients.

Cell culture and xenograft studies using androgen receptor (AR)-positive castration-resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over-expressing AR) suggest that androgens may suppress the growth of AR-rich prostate cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of testosterone cause greater growth inhibition of relapsed tumors. Manipulating androgen/AR signaling may therefore be a potential therapy for AR-positive advanced prostate cancer.

 

[zkt]

So we have a situation somewhat analogous to antibiotic resistant bacteria on steroids. (Un) natural selection at its most fucked up.
Never thought much of the androgen deprivation therapy in the first place.

 

[Makloda]

My Androstanediol Glucuronide tested way too low and so often I just feel my prostate being denied the hormones needed and it has been this way for years. I feel verry worried but no doctor takes me seriously.

 

[zkt]

Maybe you need some Androhard !

 

[BBC3]

Sure thats great. Bill Roberts told me recently in a post that I should not refer to testosterone as a "master Hormone". Well thats exactly what it is. Afterall, it will only become what your body is set up to turn it into. Which will be estrogens in ALL cases of fat or lazy old men - like me. I DO NOTE WHERE THE REFER TO ADDITIONAL USE OF AI'S.

Sadly, again the perfect example of the complete failure of medical science to acknowledge TRUE HORMONE CONVERSION RATES/PROFILES. 2500ng/dl - BUT TO WHAT?? Doesn't matter anyway because one can in theory use an additional 1-3 mgs/day (I speculate if they are lacking that much for WHATEVER DEMAND IS PRESENT) of SyN-T and not acknowledge an increase in Serum count!! Why would they if it is being used??!!??

THE POSITIVE I see in this study is that perhaps it will soon be acknowledged the legitimate use of STEROIDS in medicine, and not just testosterone. Because OBVIOUSLY the solution is the addition of ANROGENS and NOT Testosterone. The notion that they can supp testosterone and achieve an accurate androgenic result is ABSURD. Even with the use of an AI, I am betting the body circumvents by upping enzyme production to meet TRUE METABOLISM TRANSACTIONS. So while they will sit there and measure a now seemingly lowered estrogen SERUM COUNT, the body will make all it needs and based on the subject's estrogen generating factors/propensity. In the end you will have old guys getting all the excess estrogen (not showing in serums) and the only ones that stand a chance are those that also have androgen deficiencies in equal RELATIVE HEALTHY PROPORTIONS - in short only those who are short on TT due to age related production slow down not SOLELY based on estrogen generating factors. The TRUE TRT Candidates. So this should account for any failures in the principle studies.... The healthy subjects will benefit from added TT, and the Fatties will die twice as fast, and in lieu of the AI...:drooling:

[This IS NOT a typo! The research calls for testosterone use in PrCa. Moreover, at levels of 2500-3500 ng/dL, which is north of 200 mg/week.]

Androgens As Therapy For Androgen Receptor Positive Castration Resistant Prostate Cancer

Based on the results from the researchers’ model, patients developing relapsed hormone-refractory prostate tumors after androgen ablation therapy should be biopsied for expression level of Androgen Receptor (AR) protein in tumors. Intermittent Androgen Deprivation (IAD) and/or administration of exogenous androgen at a concentration 2500-3500 ng/dl will benefit patients with AR-rich relapsed tumors by suppressing tumor growth, improving quality of life, and reducing risks for cardiovascular diseases and diabetes. Combined treatment of androgen ablation therapy with anti-androgen causes a rapid and irreversible selection of more aggressive advanced prostate cancer cells. Exogenous androgen treatment can cause regression of these tumors and a subgroup of these tumors will disappear.

Androgen deprivation therapy alone may promote a slow adaptation to androgen ablation-resistance, thus shortening the period of androgen deprivation therapy may retard the diseases progression and reduce side effects. Aromatase inhibitors should be considered in combination with androgen treatment to prevent the conversion of testosterone to estradiol (E2) by aromatase to avoid potential cardiac toxicity. Since several clinical trials already confirmed that testosterone is a safe, feasible, and reasonably well-tolerated therapy for men with early hormone-refractory prostate cancer, we believe that manipulating androgen/AR signaling can be a potential therapy for AR-positive advanced prostate cancer.


Chuu CP, Kokontis JM, Hiipakka RA, et al. Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer. J Biomed Sci 2011;18:63. Journal of Biomedical Science | Full text | Androgens as Therapy for Androgen Receptor-Positive Castration-Resistant Prostate Cancer

Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in Western countries. While surgery is often successful for organ-confined prostate cancer, androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. Shortening the period of androgen ablation therapy may benefit prostate cancer patients. Intermittent Androgen Deprivation therapy improves quality of life, reduces toxicity and medical costs, and delays disease progression in some patients.

Cell culture and xenograft studies using androgen receptor (AR)-positive castration-resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over-expressing AR) suggest that androgens may suppress the growth of AR-rich prostate cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of testosterone cause greater growth inhibition of relapsed tumors. Manipulating androgen/AR signaling may therefore be a potential therapy for AR-positive advanced prostate cancer.

 

[Michael Scally MD]

Botto H, Neuzillet Y, Lebret T, Camparo P, Molinie V, Raynaud JP. High incidence of predominant Gleason pattern 4 localized prostate cancer is associated with low serum testosterone. J Urol 2011;186(4):1400-5. Elsevier

PURPOSE: We characterized the aggressiveness of prostate cancer by Gleason score and predominant Gleason pattern in relation to preoperative serum testosterone.

MATERIALS AND METHODS: In a prospective study serum total testosterone was measured preoperatively in patients referred to our department from January 2007 to January 2011 for radical prostatectomy. Gleason score and predominant Gleason pattern were determined in prostate biopsy and prostate tissue specimens.

RESULTS: A total of 431 patients were enrolled in the study. In biopsies a predominant Gleason pattern 4 was observed in 72 patients (17%). In prostate specimens the predominant Gleason pattern 4 increased to 132 patients (31%). In the 132 patients total testosterone was lower than in the 299 with predominant Gleason pattern 3 (4.00 vs 4.50 ng/ml, p = 0.001), prostate specific antigen was higher (8.4 vs 6.6 ng/ml, p <0.00001), and extraprostatic extension and positive margins were noted more often (49% vs 20% and 23% vs 14%, p <0.000001 and 0.02, respectively). The 62 patients with total testosterone less than 3.0 ng/ml were larger (mean 7 kg, p = 0.0001) with a higher body mass index (mean 0.5 kg/m(2), p <0.000001). They had a higher percent of Gleason score with predominant Gleason pattern 4 (47% vs 28%, p = 0.002).

CONCLUSIONS: Low total testosterone is associated with a higher percent of predominant Gleason pattern 4, a signature of prostate cancer aggressiveness. Tumor aggressiveness cannot be accurately estimated by biopsy Gleason score and predominant Gleason pattern. Preoperative total testosterone should be added to prostate specific antigen determination to improve management for prostate cancer.