Prostate ...

[Michael Scally MD]

Yu C-C, Huang S-P, Lee Y-C, et al. Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer. PLoS ONE 2013;8(1):e54627. PLOS ONE: Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT.

A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism.

We found that after adjusting for known risk factors in multivariate Cox regression models, AKR1C3 rs12529 and AR-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (P?0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (P<0.001).

Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.

 

[Michael Scally MD]

Resnick MJ, Koyama T, Fan K-H, et al. Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer. New England Journal of Medicine 2013;368(5):436-45. MMS: Error

BACKGROUND - The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy.

METHODS - The Prostate Cancer Outcomes Study (PCOS) enrolled 3533 men in whom prostate cancer had been diagnosed in 1994 or 1995. The current cohort comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis. We used multivariable propensity scoring to compare functional outcomes according to treatment.

RESULTS - Patients undergoing prostatectomy were more likely to have urinary incontinence than were those undergoing radiotherapy at 2 years (odds ratio, 6.22; 95% confidence interval [CI], 1.92 to 20.29) and 5 years (odds ratio, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years. Similarly, although patients undergoing prostatectomy were more likely to have erectile dysfunction at 2 years (odds ratio, 3.46; 95% CI, 1.93 to 6.17) and 5 years (odds ratio, 1.96; 95% CI, 1.05 to 3.63), no significant between-group difference was noted at 15 years. Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (odds ratio, 0.39; 95% CI, 0.22 to 0.68) and 5 years (odds ratio, 0.47; 95% CI, 0.26 to 0.84), again with no significant between-group difference in the odds of bowel urgency at 15 years.

CONCLUSIONS - At 15 years, no significant relative differences in disease-specific functional outcomes were observed among men undergoing prostatectomy or radiotherapy. Nonetheless, men treated for localized prostate cancer commonly had declines in all functional domains during 15 years of follow-up.

 

[Michael Scally MD]

Safarinejad MR, Shafiei N, Safarinejad S. Effects of EPA, gamma-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial. Br J Nutr 2012:1-8. Cambridge Journals Online - Abstract

The main objective of the present study was to determine the potential of n-3 and n-6 fatty acids or coenzyme Q10 (CoQ10) to alter serum prostate-specific antigen (PSA) levels in normal healthy men.

A total of 504 healthy men with serum PSA level </= 2.5 ng/ml were recruited into the study. Serum PSA values were not segregated by decade of age. Participants were randomly assigned to a daily dietary supplement containing n-3 fatty acids (1.12 g of EPA and 0.72 g of DHA per capsule) (group 1, n 126), n-6 fatty acid (600 mg gamma-linolenic acid (GLA) each capsule) (group 2, n 126), CoQ10 (100 mg per capsule) (group 3, n 126) or a similar regimen of placebo (group 4, n 126) for 12 weeks. Study medication was administered as two capsules to be taken twice daily. Serum levels of PSA, EPA, DHA, GLA, lipid profile and reproductive hormones were also measured.

EPA treatment significantly reduced serum PSA level by 30.0 (95 % CI 25, 36) % (P = 0.004) from baseline. In contrast, GLA therapy significantly increased serum PSA concentration by 15.0 (95 % CI 11, 20) % (P = 0.02). CoQ10 therapy also significantly reduced serum PSA level by 33.0 (95 % CI 27, 40) % (P = 0.002). In multivariable analysis, serum values of PSA were strongly correlated with duration of EPA (r - 0.62; 95 % CI - 0.42, - 0.77; P = 0.003), n-6 (r 0.42; 95 % CI 0.31, 0.58; P = 0.02) and CoQ10 use (r - 0.77; 95 % CI - 0.56, - 0.87; P = 0.001). There were also significant correlations between serum values of DHA, EPA, GLA and CoQ10 and serum PSA levels.

The present study demonstrates that dietary supplements containing EPA, GLA or CoQ10 may significantly affect serum PSA levels.

 

[hackskii]

I noticed that after like 6 months on fish oils my flow of urine was much stronger.
I have not taken them in a year, and the flow seems to have slowed some.
I am back on them as of today.

 

[Michael Scally MD]

Salagierski M, Mulders P, Schalken JA. Predicting Prostate Biopsy Outcome Using a PCA3-based Nomogram in a Polish Cohort. Anticancer Res 2013;33(2):553-7. Predicting Prostate Biopsy Outcome Using a PCA3-based Nomogram in a Polish Cohort

BACKGROUND: Prostate Cancer Gene-3 (PCA3) is highly prostate cancer (PCa)-specific and its application holds promise in identifying men with PCa.

AIM: To determine whether the PCA3 score can be used relative to PCa clinical variables to predict biopsy outcome.

PATIENTS AND METHODS: PCA3 scores were assessed in a group of 80 patients using the Progensa assay (Gen-Probe, San Diego, CA, USA). The logistic regression algorithm was used to combine PCA3 results with the established biopsy risk factors including: age, prostate-specific antigen (PSA), digital rectal examination (DRE) and prostate volume (Pvol).

RESULTS: In univariate analyses, the Progensa PCA3 score outperformed all biopsy risk predictors. A logistic regression algorithm using: age, PCA3, PSA, DRE and Pvol increased the area under the Receiver Operating Characteristic (ROC) curve from 0.72 for PCA3-alone to 0.85.

CONCLUSION: Combining PCA3 results with PCa risk factors provides significant improvements over the use of PCA3- or PSA-alone in predicting the probability of a positive prostate biopsy.

 

[Michael Scally MD]

Fritz S, Chris B, Javier CA, et al. Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised, Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS). European urology. Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised, Placebo-controlled Avodart After Radical Therapy for Prostate

Background - Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

Objective - To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

Design, Setting, And Participants - Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

Intervention - The 5?-reductase inhibitor, dutasteride.

Outcome Measurements And Statistical Analysis - The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

Results and Limitations - Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

Conclusions - Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

 

[BBC3]

Yea, I used to hear dad report that the UROlogist noted concern that his PSA was up and after having the prostate removed. The interesting point was that HIS PROSTATE was removed. Therefore, there should have been no prostate to generate a PSA

Interestingly enough, his preferred treatment is not durestaride, its BLUE BERRIES...?!?

Can Blueberries Shrink Cancer Cells? | LIVESTRONG.COM

Whats really interesting, is that ANYONE in the states can grow blue berries in their own back yard WITH EASE...

So now, imagine you just ate blue berries every day, AND BEFORE YOU GET CANCER>..

Fritz S, Chris B, Javier CA, et al. Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised, Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS). European urology. Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised, Placebo-controlled Avodart After Radical Therapy for Prostate

Background - Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

Objective - To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

Design, Setting, And Participants - Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

Intervention - The 5?-reductase inhibitor, dutasteride.

Outcome Measurements And Statistical Analysis - The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

Results and Limitations - Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

Conclusions - Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

 

[Michael Scally MD]

Amoretti A, Laydner H, Bergfeld W. Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis. J Am Acad Dermatol. ScienceDirect.com - Journal of the American Academy of Dermatology - Androgenetic alopecia and risk of prostate cancer: A

BACKGROUND: Androgenetic alopecia (AGA) is a genetically determined skin condition strongly age dependent and androgens are assumed to play an important role in its development. A link between AGA and prostate cancer has been hypothesized because of their similar risk factors.

OBJECTIVE: We sought to systematically review the evidence available on the association between AGA and risk of prostate cancer.

METHODS: We searched the electronic databases MEDLINE and Cochrane for studies examining the association between AGA and risk of prostate cancer. We estimated pooled odds ratios (OR) and 95% confidence intervals. We also analyzed the OR for individual hair loss patterns, as defined by the Hamilton scale.

RESULTS: A total of 7 case-control studies including 8994 patients-4078 cases and 4916 controls-were reviewed. One cohort study was identified but did not meet our inclusion criteria. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58). LIMITATIONS: Only case-control studies, which may be subject to bias, met the inclusion criteria for this meta-analysis.

CONCLUSIONS: Vertex pattern AGA was associated with a significant increased risk of prostate cancer. Any pattern AGA did not show a significant increase in the risk of prostate cancer.

 

[BBC3]

So then bald guys get it more... And it dont matter what type balding pattern...

Amoretti A, Laydner H, Bergfeld W. Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis. J Am Acad Dermatol. ScienceDirect.com - Journal of the American Academy of Dermatology - Androgenetic alopecia and risk of prostate cancer: A

BACKGROUND: Androgenetic alopecia (AGA) is a genetically determined skin condition strongly age dependent and androgens are assumed to play an important role in its development. A link between AGA and prostate cancer has been hypothesized because of their similar risk factors.

OBJECTIVE: We sought to systematically review the evidence available on the association between AGA and risk of prostate cancer.

METHODS: We searched the electronic databases MEDLINE and Cochrane for studies examining the association between AGA and risk of prostate cancer. We estimated pooled odds ratios (OR) and 95% confidence intervals. We also analyzed the OR for individual hair loss patterns, as defined by the Hamilton scale.

RESULTS: A total of 7 case-control studies including 8994 patients-4078 cases and 4916 controls-were reviewed. One cohort study was identified but did not meet our inclusion criteria. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58). LIMITATIONS: Only case-control studies, which may be subject to bias, met the inclusion criteria for this meta-analysis.

CONCLUSIONS: Vertex pattern AGA was associated with a significant increased risk of prostate cancer. Any pattern AGA did not show a significant increase in the risk of prostate cancer.

 

[Michael Scally MD]

So then bald guys get it more... And it dont matter what type balding pattern...

No! It is associated with Vertex balding.

CONCLUSIONS: Vertex pattern AGA was associated with a significant increased risk of prostate cancer.

 

[Michael Scally MD]

Mejak SL, Bayliss J, Hanks SD. Long Distance Bicycle Riding Causes Prostate-Specific Antigen to Increase in Men Aged 50 Years and Over. PLoS One 2013;8(2):e56030. PLOS ONE: Long Distance Bicycle Riding Causes Prostate-Specific Antigen to Increase in Men Aged 50 Years and Over

OBJECTIVES: To investigate whether bicycle riding alters total prostate-specific antigen (tPSA) serum concentrations in healthy older men.

METHODS: 129 male participants, ranging in age from 50 to 71 years (mean 55 years), rode in a recreational group bicycle ride of between 55 and 160 kilometers. Blood samples for tPSA analysis were drawn within 60 minutes before starting, and within 5 minutes after completing the ride. The pre-cycling and post-cycling tPSA values were log transformed for normality and compared using paired t-tests. Linear regression was used to assess the relationship between changes in tPSA with age and distance cycled.

RESULTS: Bicycle riding caused tPSA to increase by an average of 9.5% (95% CI = 6.1-12.9; p<0.001) or 0.23 ng/ml. The number of participants with an elevated tPSA (using the standard PSA normal range cut-off of 4.0 ng/ml) increased from two pre-cycle to six post-cycle (or from five to eight when using age-based normal ranges). Univariate linear regression analysis revealed that the change in tPSA was positively correlated with age and the distance cycled.

CONCLUSIONS: Cycling causes an average 9.5% increase in tPSA, in healthy male cyclists >/=50 years old, when measured within 5 minutes post cycling. We considered the increase clinically significant as the number of participants with an elevated PSA, according to established cut-offs, increased post-ride. Based on the research published to date, the authors suggest a 24-48 hour period of abstinence from cycling and ejaculation before a PSA test, to avoid spurious results.

 

[BBC3]

Hi Doc, not splitting hairs to argue with you. Just pointing out some failure in the fundamentals of the whole notion. Of course there is always safety in ambiguity.

On topic, but opposing - Here is an interesting one:
http://www.behav.org/kabai/abstracts/kabai_alopecia_prostate_cancer.pdf
So I wonder does wearing a hat make a difference... LOL[)]

I guess I was pointing out that what I suspected is that "AGA" is MPB (Male pattern baldness), and is there really any other kind.?? And that it was my belief that the article was describing essentially that MPB corolates with PC, and that any other kind of condition (rare) of hair loss may not.???

Well I guess then the article/study is referring to the crown or "bald spot", and not the front temporal region. I have never really paid attention. I believe the problem here lies in the poor use of terms by the study. I saw a couple of definitions citing the "vertex" as the point at which first rears at child birth, which I recall is a gross disfiguration of head and presenting "skull cap" first...

vertex - definition of vertex in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia.

So I just think of the highest point of the head being a center line from the top of the frontal region to the top of the rear crown.

The term/acronym "AGA", as androgenic alopecia - is there really any other kind, That is other than general head hair thinning uniform throughout, which is rare as not related to androgens regardless anyway. STILL, is there any form of male hairloss that is not androgen related and still involving the front upper temporal to some degree. Its rare to see a man with a flat out bald spot and no frontal hair loss... short of medical conditions otherwise, of course...

I found a related article here:
John Libbey Eurotext : Éditions médicales et scientifiques France : revues, médicales, scientifiques, médecine, santé, livres - Texte intégral de l'article
This is a good article from 2011 I think that has lots of info that could be interpreted all kinds of ways...:
http://www.univermind.com/publicaciones/Galerada FINAL.pdf

I still cant find access to the full article referenced in the original post....

Is it safe to assume then that they are referring really to Male Pattern Baldness?:
Male Pattern Baldness | Androgenetic Alopecia | AGA Mens Hair Loss | Lam Institute for Hair Restoration

Ironically, in my experience with friends and general discussion with other men's life experience, it is also the crown vertex area which is most susceptible to temporary hair loss as stress/circulatory induced, as well as other more temporary conditions...!! I knew a guy once that got so stressed he completely lost the crown area of his hair, and it all came back within a year. I suspect its due to the furthest point which the heart pumps blood, and hence the first to suffer from lack of...:
The Crown: Important or Not? | Spex uk hair transplant veteran

This presentation is incomplete as is, but in a laymans concept as the word "vertex", one would think that #34 in the picture would be included.?:
Vertex Scalp - Pictures - Wellsphere

Further vertex definitions:
http://en.wikipedia.org/wiki/Vertex_(geometry)
vertex - definition of vertex by the Free Online Dictionary, Thesaurus and Encyclopedia.

Why cant they just say "crown"? The "highest point" is not the "vertex" of the skull on anyone I don't think..? Looking a guys with MPB, the crown which goes first, and I believe the article is referring, is on the downslope of the rear of the skull. AGAIN, I suspect selfish omniscient power flex by medical science's limited approach and perspective...

Somehow, society has trained me to see a guy with a bald spot and think to myself that he is due for all kinds of androgen related conditions inclusive of cancer! It has NOT trained me to see a bald guy and wonder what other underlying conditions my contribute to future cancer then fueled by high androgen levels. Like all metabolic life, both androgens and estrogens are required in all cells for activity - to some degree, but usually BOTH. My suspicion is that androgens are metabolized much more quickly in the male body as compared to estrogens. As possibly denoted by a potentially more markedly increase in testicular atrophy related to the supplementing of exogenous testosterone by men with greater proportions of androgen tissue factors/population. Thus, of course men capable of metabolizing more androgens and their derivatives will have greater collateral cellular response in conditions of illness, as well as health. In short, I suspect improper or excess estrogen activity my CAUSE failures like many cancers, and then all normal hormones fuel the progression and growth reflective of the normal hormonal conditions. Wouldn't it be the kicker that while estrogen makes life, it is also the ender of - and from a sense more so of a SYSTEM FAILURE, rather than NORMAL WEAR.

*** Consider (1) woman and (1000) men can breed and populate a planet GENETICALLY healthy. (1) man and (1000) women will breed a society of GENETIC INCEST....! Possibly? He would be a happy camper..! Could just doubling the number of men to (2) completely negate these odds? Do the male genetics supersede the woman's in the final offspring's profile. Or is it the other way around...:drooling: The second scenario would breed the population 1000 x's faster - of course.. How many folks kids do YOU know that look predominantly like their father, or a father from past??!! Is than an order for genetic control in precedence of reproductive hiearchy??

IF ANY OF THE PREMISE I HAVE LAID DOWN ABOVE IS CORRECT (with the exception of the last paragraph - lol), then we have to denote the following:

1. This is potentially subversively misleading back to the old premise that ANDROGENS are associated with PC.
2. The study makes no discern for conditions leading up to prostate cancer diagnosis. It is my personal belief that estrogens MAY be the culprit in the culmination of PC, and that the hormones (androgens & estrogens) then feed the corruption which is already complete in action. Of course that makes sense as hormones appear to be required in all normal cellular metabolic activity throughout the body.
3. Could it be possible that guys with higher scalp presented androgen activity are also suspect to higher cancer activity once developed.diagnosed? and that is all there is to it? After all, I doubt they included 65-75 year old males in their study?? The abstract speaks of "age related" but they make no mention of the study group profile specifics?!?!
4. What about all the old coots with no hair and no prostate cancer?!! Again, a study which appears to service either its self, or anyone wishing to utilize it in a medically $$ productive way..
5. One thing it does bring to mind, is that if prostate cancer correlates with androgen related hair loss, and in any way, then how does this relate to underlying estrogen related metabolic conditions in these individuals.??
6. Do old guys with full heads of hair get prostate cancer? Young guys? Logic would suggest that they would have an estrogen positive imbalance in hormone activity. So why not all dead of estrogen related cancer. Is this proof of the slower rate of hormonal metabolism of estrogens? Is that proof that if estrogens are mostly responsible for making cancer in men, that it requires androgens to fuel and grow it, and at a proportionately reflective rate?

Some more interestingly related articles:
An Error Occurred Setting Your User Cookie

** So is it my current and past high estrogen generating principles protecting me from going completely bald, or is it my LACK of androgen principles that is not present to cause the hairloss? Based on my premises, I am the poster child from prostate cancer, and early before 50, as I have high estrogen factors while also having considerable androgen factors remaining in place...! The CAUSE and the FUEL according to ME... It would certainly suggest the i am far from MODERATE in lifestyle and abundant in too much of everything. While it appears MODERATE (in my mind)in that i am not overly abundant as WEIGHTED to one side or the other - hormonally speaking. This would be a test of receptor competition among different tissue types. Or even a test of the presence of certain receptors as possibly influences by other hormone factors, both biologically produced as well as exogenously supplied. Does one hormone facet balance or protect the other. Or does one hormone facet actually influence tissue receptor growth and generation via overabundance of SUPPLY??

The only thing that is for sure is that my shit has not been working right for 7 years now at least. I have neglected these physical indications too long without making any effort to change the underlying physical conditions which may be contributing. Genetic failure, or self induced results.??!!? A combination I am certain, but the weight on the second greater I fear...

Insanity Lamented and SQUARED indeed...

No! It is associated with Vertex balding.

 

[BBC3]

Doc, have you found any good articles relating PC to obesity? I found this one interesting as they are really going beyond the simple premise of basic hormone influence. I think its just an interpretation by a group based on other data, but seem to provide enough for interest. Though, I am also looking to see about correlation of body fat and PC in study documentation.

Obesity promotes prostate cancer by altering gene regulation

 

[Michael Scally MD]

Elshafei A, Moussa AS, Hatem A, et al. Does Positive Family History of Prostate Cancer Increase the Risk of Prostate Cancer on Initial Prostate Biopsy? Urology. ScienceDirect.com - Urology - Does Positive Family History of Prostate Cancer Increase the Risk of Prostate Cancer on Initial Prostate Biopsy?

OBJECTIVE: To assess the role of family history (FH) in the risk of a positive prostate biopsy (PBx) in a large North American biopsy population as earlier reports showed increased risk of prostate cancer (PCa) in men with a FH, but the risk has been limited to low grade prostate cancer in smaller studies, and the REDUCE trial found no such risk in North American patients.

METHODS: We evaluated 4360 men undergoing initial extended biopsy (8-14 cores). Indications were elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Variables including age, FH of PCa, race, PSA, and DRE results were included in our analysis to assess risk factors associated with PCa, high-grade prostate cancer (HGPCa), and low-grade prostate cancer (LGPCa).

RESULTS: Two hundred sixty-eight patients had an FH of PCa whereas 4092 had negative FH. Positive biopsy was found in 1976 patients with HGPCa in 1149 and LGPCa in 827. Among 268 patients with an FH, overall PCa was found in 144 of 268 patients (54%); HGPCa in 79 of 144 patients (55%) and LGPCa in 65 of 144 patients (45%). FH was a significant risk factor for PCa, HGPCa, and LGPCa in univariate and multivariate analysis (P = .0001, .02, and .02, respectively). Also, FH was associated with high-risk benign pathology in the form of atypical small acinar cell proliferation (ASAP) or high-grade prostatic intraepithelial neoplasm (HGPIN) (P = .04).

CONCLUSION: Men in North America with an FH of PCa who undergo prostate biopsy are more likely to be diagnosed with both HGPCa and LGPCa.

 

[Michael Scally MD]

Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database Syst Rev 2013;1:CD004720. Screening for prostate cancer - The Cochrane Library - Ilic - Wiley Online Library

BACKGROUND: Any form of screening aims to reduce disease-specific and overall mortality, and to improve a person's future quality of life. Screening for prostate cancer has generated considerable debate within the medical and broader community, as demonstrated by the varying recommendations made by medical organizations and governed by national policies. To better inform individual patient decision-making and health policy decisions, we need to consider the entire body of data from randomised controlled trials (RCTs) on prostate cancer screening summarised in a systematic review. In 2006, our Cochrane review identified insufficient evidence to either support or refute the use of routine mass, selective, or opportunistic screening for prostate cancer. An update of the review in 2010 included three additional trials. Meta-analysis of the five studies included in the 2010 review concluded that screening did not significantly reduce prostate cancer-specific mortality. In the past two years, several updates to studies included in the 2010 review have been published thereby providing the rationale for this update of the 2010 systematic review.

OBJECTIVES: To determine whether screening for prostate cancer reduces prostate cancer-specific mortality or all-cause mortality and to assess its impact on quality of life and adverse events.

SEARCH METHODS: An updated search of electronic databases (PROSTATE register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CANCERLIT, and the NHS EED) was performed, in addition to handsearching of specific journals and bibliographies, in an effort to identify both published and unpublished trials.

SELECTION CRITERIA: All RCTs of screening versus no screening for prostate cancer were eligible for inclusion in this review.

DATA COLLECTION AND ANALYSIS: The original search (2006) identified 99 potentially relevant articles that were selected for full-text review. From these citations, two RCTs were identified as meeting the inclusion criteria. The search for the 2010 version of the review identified a further 106 potentially relevant articles, from which three new RCTs were included in the review. A total of 31 articles were retrieved for full-text examination based on the updated search in 2012. Updated data on three studies were included in this review. Data from the trials were independently extracted by two authors.

MAIN RESULTS: Five RCTs with a total of 341,342 participants were included in this review. All involved prostate-specific antigen (PSA) testing, with or without digital rectal examination (DRE), though the interval and threshold for further evaluation varied across trials. The age of participants ranged from 45 to 80 years and duration of follow-up from 7 to 20 years. Our meta-analysis of the five included studies indicated no statistically significant difference in prostate cancer-specific mortality between men randomised to the screening and control groups (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.86 to 1.17). The methodological quality of three of the studies was assessed as posing a high risk of bias. The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were assessed as posing a low risk of bias, but provided contradicting results. The ERSPC study reported a significant reduction in prostate cancer-specific mortality (RR 0.84, 95% CI 0.73 to 0.95), whilst the PLCO study concluded no significant benefit (RR 1.15, 95% CI 0.86 to 1.54). The ERSPC was the only study of the five included in this review that reported a significant reduction in prostate cancer-specific mortality, in a pre-specified subgroup of men aged 55 to 69 years of age. Sensitivity analysis for overall risk of bias indicated no significant difference in prostate cancer-specific mortality when referring to the meta analysis of only the ERSPC and PLCO trial data (RR 0.96, 95% CI 0.70 to 1.30). Subgroup analyses indicated that prostate cancer-specific mortality was not affected by the age at which participants were screened. Meta-analysis of four studies investigating all-cause mortality did not determine any significant differences between men randomised to screening or control (RR 1.00, 95% CI 0.96 to 1.03). A diagnosis of prostate cancer was significantly greater in men randomised to screening compared to those randomised to control (RR 1.30, 95% CI 1.02 to 1.65). Localised prostate cancer was more commonly diagnosed in men randomised to screening (RR 1.79, 95% CI 1.19 to 2.70), whilst the proportion of men diagnosed with advanced prostate cancer was significantly lower in the screening group compared to the men serving as controls (RR 0.80, 95% CI 0.73 to 0.87). Screening resulted in a range of harms that can be considered minor to major in severity and duration. Common minor harms from screening include bleeding, bruising and short-term anxiety. Common major harms include overdiagnosis and overtreatment, including infection, blood loss requiring transfusion, pneumonia, erectile dysfunction, and incontinence. Harms of screening included false-positive results for the PSA test and overdiagnosis (up to 50% in the ERSPC study). Adverse events associated with transrectal ultrasound (TRUS)-guided biopsies included infection, bleeding and pain. No deaths were attributed to any biopsy procedure. None of the studies provided detailed assessment of the effect of screening on quality of life or provided a comprehensive assessment of resource utilization associated with screening (although preliminary analyses were reported).

AUTHORS' CONCLUSIONS: Prostate cancer screening did not significantly decrease prostate cancer-specific mortality in a combined meta-analysis of five RCTs. Only one study (ERSPC) reported a 21% significant reduction of prostate cancer-specific mortality in a pre-specified subgroup of men aged 55 to 69 years. Pooled data currently demonstrates no significant reduction in prostate cancer-specific and overall mortality. Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent, and moderate in severity. Overdiagnosis and overtreatment are common and are associated with treatment-related harms. Men should be informed of this and the demonstrated adverse effects when they are deciding whether or not to undertake screening for prostate cancer. Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue; therefore, men who have a life expectancy less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial. No studies examined the independent role of screening by DRE.

 

[BBC3]

Really, the most shocking point I find in this article is that it would appear that a "prostate biopsy" consists on not ONE, but 8-16 "cores"...?? YEAOUCHHH !!!!!!!!!!!!!!!!!!!!. I mean really, would there be anything left??!!! Can anyone please cite the actual diameter of a "core tissue sample", and as it relates to PIZ SIZE for us laymans. Seems I recall a blood or plasma donation is done with about a 17ga. pin. I also recall that this is a fucking monster.!!! Obviously, the design of the/a "needle/Pin" which is used for the purpose of fluid injection or removal is to INCISE or CUT ONLY, and not completely detach any given segment of tissue as removed/removable, but certainly we can draw some similarity for the purpose of discussion.??

SO really, after 16 passes with a FLOUNDERING GIG - is there really any thing left??!! You really almost have to wonder how many folks incidentally had any cancerous cells completely removed in this procedure/ and incidentally?!?!? LOL But would an otherwise healthy sex function even exist after a "biopsy", if it happend to be one of the rare cases where the person had a working pecker by that age?? Really!

Finally, all this begs the question - How does PC correlate with a functioning male genitalia? Does staying in shape enough to be able to get normal wood maintain the conditions unfavorable to prostate cancer, and as a simply marker by notion alone.? Psychological conditions aside, how many OLDER men with no complaints of impotence, ED, or physical sexual failures of any type area actually diagnosed with PC/and regardless of history or genetic propensity?... Does HAVING the ability to pound some muff insure a healthy prostate?

Elshafei A, Moussa AS, Hatem A, et al. Does Positive Family History of Prostate Cancer Increase the Risk of Prostate Cancer on Initial Prostate Biopsy? Urology. ScienceDirect.com - Urology - Does Positive Family History of Prostate Cancer Increase the Risk of Prostate Cancer on Initial Prostate Biopsy?

OBJECTIVE: To assess the role of family history (FH) in the risk of a positive prostate biopsy (PBx) in a large North American biopsy population as earlier reports showed increased risk of prostate cancer (PCa) in men with a FH, but the risk has been limited to low grade prostate cancer in smaller studies, and the REDUCE trial found no such risk in North American patients.

METHODS: We evaluated 4360 men undergoing initial extended biopsy (8-14 cores). Indications were elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Variables including age, FH of PCa, race, PSA, and DRE results were included in our analysis to assess risk factors associated with PCa, high-grade prostate cancer (HGPCa), and low-grade prostate cancer (LGPCa).

RESULTS: Two hundred sixty-eight patients had an FH of PCa whereas 4092 had negative FH. Positive biopsy was found in 1976 patients with HGPCa in 1149 and LGPCa in 827. Among 268 patients with an FH, overall PCa was found in 144 of 268 patients (54%); HGPCa in 79 of 144 patients (55%) and LGPCa in 65 of 144 patients (45%). FH was a significant risk factor for PCa, HGPCa, and LGPCa in univariate and multivariate analysis (P = .0001, .02, and .02, respectively). Also, FH was associated with high-risk benign pathology in the form of atypical small acinar cell proliferation (ASAP) or high-grade prostatic intraepithelial neoplasm (HGPIN) (P = .04).

CONCLUSION: Men in North America with an FH of PCa who undergo prostate biopsy are more likely to be diagnosed with both HGPCa and LGPCa.

 

[Michael Scally MD]

Muller RL, Gerber L, Moreira DM, Andriole G, Castro-Santamaria R, Freedland SJ. Serum Testosterone and Dihydrotestosterone and Prostate Cancer Risk in the Placebo Arm of the Reduction by Dutasteride of Prostate Cancer Events Trial. Eur Urol. ScienceDirect.com - European Urology - Serum Testosterone and Dihydrotestosterone and Prostate Cancer Risk in the Placebo Arm of the Reduction by Dutasteride of Prostate Cancer Events Trial

BACKGROUND: Findings of studies on the association between androgens and prostate cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA) levels, thereby influencing biopsy recommendations. Also, androgens may stimulate prostate growth at very low levels with no additional effects at higher levels (saturation model).

OBJECTIVE: To test whether androgens were associated with PCa risk in the placebo arm of a prospective study in which biopsies were performed regardless of PSA level.

DESIGN, SETTING, AND PARTICIPANTS: Of 8122 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men (50.1%) received placebo. Key entry criteria were PSA 2.5-10 ng/ml and one prior negative biopsy.

INTERVENTION: Per-protocol biopsies at 2 and 4 yr; for-cause biopsies at physician discretion.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression was used to test the association between baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76 nmol/l) compared with normal baseline androgen levels.

RESULTS AND LIMITATIONS: Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were analyzed. Androgen levels tested continuously or by quintiles were generally unrelated to PCa detection or grade. PCa detection was similar among men with low compared with normal baseline testosterone levels (25.5% and 25.1%; p=0.831). In secondary analysis, higher testosterone levels at baseline were associated with higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06-1.43; p=0.006) only if men had low baseline testosterone (<10nmol/l). For men with normal baseline testosterone (>/=10 nmol/l), higher testosterone levels at baseline were unrelated to PCa risk (p=0.33). No association was found for DHT and PCa (all p>0.85).

CONCLUSIONS: Baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies using an a priori defined hypothesis.

 

[Michael Scally MD]

Ferraldeschi R, Sharifi N, Auchus RJ, Attard G. Molecular Pathways: Inhibiting steroid biosynthesis in prostate cancer. Clin Cancer Res. Molecular Pathways: Inhibiting steroid biosynthesis in prostate cancer.

A significant proportion of castration-resistant prostate cancers (CRPC) remain driven by ligand activation of the androgen receptor. Although the testes are the primary source of testosterone, testosterone can also be produced from peripheral conversion of adrenal sex hormone precursors dehydroepiandrosterone (DHEA) and androstenedione (AD) in the prostate and other tissues. CYP17A1 catalyzes two essential reactions in the production of DHEA and androstenedione: the hydroxylation (hydroxylase activity) and the subsequent cleavage of the C17-20 side-chain (lyase activity). Potent and selective inhibition of CYP17A1 by abiraterone depletes residual non-gonadal androgens and is an effective treatment for CRPC. Elucidation of the mechanisms that underlie resistance to abiraterone will inform on the development of novel therapeutic strategies post abiraterone. Preclinical evidence that androgen biosynthesis in prostate cancer cells does not necessarily follow a single dominant pathway and residual androgens or alternative ligands (including administered glucocorticoids) can reactivate androgen receptor signaling supports co-targeting of more than one enzyme involved in steroidogenesis and combining a CYP17A1 inhibitor with an anti-androgen. Furthermore, given the drawbacks of 17alpha-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid co-administration.

 

[Michael Scally MD]

Shukla-Dave A, Hricak H. Role of MRI in prostate cancer detection. NMR Biomed. Role of MRI in prostate cancer detection - Shukla-Dave - 2013 - NMR in Biomedicine - Wiley Online Library

The standard approach for the detection of prostate cancer -- prostate-specific antigen (PSA) screening followed by transrectal ultrasonography (TRUS)-guided biopsy -- has low sensitivity and provides limited information about the true extent and aggressiveness of the cancer. Improved methods are needed to assess the extent and aggressiveness of the cancer and to identify patients who will benefit from therapy. In recent years, there has been tremendous development of acquisition and processing tools for physiological and metabolic MRI techniques which play a potential role in the detection, localization and characterization of prostate cancer, such as dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI) and/or proton MR spectroscopic imaging (1 H MRSI). The standard protocol for prostate MRI without the use of a contrast agent involves multi-planar T1 -weighted MRI, T2 -weighted MRI and DW-MRI. This review discusses the potential role of MRI in the detection of prostate cancer, specifically describing the status of MRI as a tool for guiding targeted prostate biopsies and for detecting cancer in the untreated and treated gland. In addition, future areas of MRI research are briefly discussed. Groups conducting clinical trials should consider the recommendations put forward by the European Consensus Meeting, which state that the minimum requirements for prostate MRI are T1 -weighted MRI, T2 -weighted MRI, DCE-MRI (which involves the use of a contrast agent) and DW-MRI with a pelvic phased-array coil and propose the use of transperineal template mapping biopsies as the optimal reference standard.

 

[Michael Scally MD]

Finasteride: No Prostate Cancer Survival Benefit

Background: As finasteride could reduce by 25% the number of prostate cancers (PCa) diagnosed in the U.S. annually, the public health benefit of prostate cancer prevention could be enormous. We performed a survival analysis to assess for any evidence of increased risk of death in men randomized to finasteride, a potential indicator of a ‘true’ increased risk of high grade (HG) disease in the PCPT.

Methods: A Social Security Death Index search was conducted on all randomized men to ascertain date of death. Cox proportional hazards models adjusting for known risk factors for overall survival and survival from time of diagnosis of PCa overall, low grade (LG) and HG were used to estimate hazard ratios (HR) and construct 95% confidence intervals to determine if survival on finasteride and placebo were equivalent.

Results: A total of 5,128 deaths have been reported; 2,584 men on finasteride and 2544 on placebo. 15-year survival rates for all randomized men in each arm is 78%. The HR for overall survival on finasteride compared to placebo is 1.04 (95% CI 0.96, 1.10, p=.19). 10-year survival from diagnosis for men with PCa was slightly higher for men randomized to finasteride (10-year survival 83% vs. 81%) but not statistically significant (HR= 0.87, 95% CI 0.73 - 1.04, p=.14). For the men with HG PCa, there was no evidence of worse survival on finasteride (HR= 1.01; 95% CI 0.73, 1.14, p=.97) while those diagnosed with LG disease finasteride had superior survival (HR= 0.73; 95% CI 0.57, 0.94, p=.01).

Conclusions: For men in PCPT with PCa there was no difference in survival from diagnosis date, a slightly-superior 10-year survival with finasteride and a statistically-superior survival among men with LG tumors in the finasteride group. A potential explanation for this phenomenon could be a lead-time bias. Arguing against this bias is the identical survival of HG PCa in both groups. Another potential explanation is that the men with LG PCa on placebo include a greater number with undetected HG disease; HG tumors in men on finasteride were more likely detected due to the improved performance of prostate biopsy. With follow-up of 18 years, finasteride administration for 7-years does not appear to affect mortality but significantly reduces the risk of a PCa diagnosis.

Goodman PJ, Thompson IM, Tangen CM, et al. Long-term survival of subjects in the prostate cancer prevention trial. Program and abstracts of the 2013 Genitourinary Cancers Symposium; February 14-16, 2013; Orlando, Florida. Abstract 10. https://meetinglibrary.asco.org/print/597781