Prostate ...

[Michael Scally MD]

Rosenberg MT, Spring AC, David Crawford E. Prostate cancer and the PCP: the screening dilemma. International Journal of Clinical Practice. http://onlinelibrary.wiley.com/doi/10.1111/ijcp.12745/full

The primary care provider (PCP) is in a difficult position with the myriad of recommendations regarding the screening of prostate cancer. New guidelines suggest that testing the general population lacks evidence whereas others state that it is appropriate in the correct patient. Universally all of the recommendations state that the PCP should involve the patient in a ‘shared decision process’ with whichever guideline they chose to follow. Regardless of the provider's belief or agreement with any of the guidelines one must question the feasibility of this process. Time and lack of urologic education are both obstacles for the PCP who is the gatekeeper for patient evaluation. In this perspective piece, the origin of the prostate-specific antigen (PSA) test is explored along with what the value truly means. The implementation of shared decision making is objectively reviewed as well as the ramifications of the entire process. In an endeavour to simplify screening for prostate cancer a logically based algorithm is offered.

 

[MR10X]

PCP did a DRE and PSA blood test...DRE was fine and no lumps or enlargement.... PSA 7.7 sent me to a Urologist.

 

[Michael Scally MD]

Mateo J, Carreira S, Sandhu S, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. New England Journal of Medicine 2015;373(18):1697-708. http://www.nejm.org/doi/full/10.1056/NEJMoa1506859

BACKGROUND - Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibition with olaparib.

METHODS - We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.

RESULTS - Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes — including BRCA1/2, ATM, Fanconi’s anemia genes, and CHEK2 — in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.

CONCLUSIONS - Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate.

 

[Michael Scally MD]

A Hypothetical Model Illustrates The Role Of Age-Related Declines In Testosterone (T) In The Development Of Pca

Two key components are included in our dynamic model: the magnitude of the age-related declines in testosterone and the individual-based threshold level of testosterone to maintain the normal function of prostate gland.

Our model emphasizes that the absolute value of testosterone measured at a single point is not indicative of PCa risk. Instead, the magnitude of the age-related declines in testosterone is a key factor.

The risk of PCa increases when testosterone levels fall below a threshold. As testosterone level falls below the threshold, prostatic cells reach the limit of their compensatory capabilities, thus impairing adaption to lower levels of testosterone and finally triggering the prostatic carcinogenesis process

Xu X, Chen X, Hu H, Dailey AB, Taylor BD. Current opinion on the role of testosterone in the development of prostate cancer: a dynamic model. BMC Cancer 2015;15(1):806. http://www.biomedcentral.com/1471-2407/15/806

BACKGROUND: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.

PRESENTATION OF THE HYPOTHESIS: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.

TESTING THE HYPOTHESIS: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis.

IMPLICATIONS OF THE HYPOTHESIS: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy.

 

[Michael Scally MD]

JAMA Prostate Specific Antigen (PSA) Screening Series [5 Articles]
[For Series Email mike.scally@asih.net (Include Title)]

Penson DF. The Pendulum of Prostate Cancer Screening. JAMA. 2015;314(19):2031-2033. http://jama.jamanetwork.com/article.aspx?articleid=2470425

Jemal A, Fedewa SA, Ma J, et al. Prostate Cancer Incidence and PSA Testing Patterns in Relation to USPSTF Screening Recommendations. JAMA. 2015;314(19):2054-2061. http://jama.jamanetwork.com/article.aspx?articleid=2470446

Sammon JD, Abdollah F, Choueiri TK, et al. Prostate-Specific Antigen Screening After 2012 US Preventive Services Task Force Recommendations. JAMA. 2015;314(19):2077-2079. http://jama.jamanetwork.com/article.aspx?articleid=2470435

Barry MJ, Hayes JH. Evaluating an Elevated Screening PSA Test. JAMA. 2015;314(19):2073-2074. http://jama.jamanetwork.com/article.aspx?articleid=2470424

Barry MJ, Hayes JH. Evaluating an Elevated Screening PSA Test. JAMA. 2015;314(19):2073-2074. http://jama.jamanetwork.com/article.aspx?articleid=2470424

 

[Michael Scally MD]

Schenk JM, Till C, Hsing AW, et al. Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial. Cancer Causes Control. http://link.springer.com/article/10.1007/s10552-015-0695-0

BACKGROUND: Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial.

METHODS: In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3alpha-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples.

RESULTS: We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA.

CONCLUSION: Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.

 

[Michael Scally MD]

Shiota M, Takeuchi A, Sugimoto M, et al. Prognostic Impact of Serum Testosterone and Body Mass Index Before Androgen-deprivation Therapy in Metastatic Prostate Cancer. Anticancer Res 2015;35(12):6925-32. Prognostic Impact of Serum Testosterone and Body Mass Index Before Androgen-deprivation Therapy in Metastatic Prostate Cancer

AIM: Although the impact of testosterone or obesity on the efficacy of androgen-deprivation therapy (ADT) has been reported, there exist few comprehensive analyses on the impact of these factors on ADT outcome. Therefore, in the present study, we investigated the relationship between serum testosterone or body mass index (BMI) and prognosis among men treated with primary ADT for metastatic prostate cancer.

PATIENTS AND METHODS: The study included fifty-six Japanese patients with prostate cancer treated at our Institution from 2000 through 2012. The relationship between serum testosterone or BMI and progression-free survival, cancer-specific survival, and overall survival among men with metastatic prostate cancer treated with primary ADT was examined.

RESULTS: The median of serum testosterone and BMI were 397 ng/dl (interquartile range (IQR), 278-464 ng/dl) and 21.9 kg/m(2) (IQR, 19.2-23.6 kg/m(2)), respectively. Median progression-free survival, cancer-specific survival, and overall survival were 23.2 months, 68.9 months, and 68.1 months, respectively.

Among clinicopathological parameters, the lowest-quartile group of serum testosterone level was a significant predictor of poor cancer-specific survival and overall survival as well as survival from castration resistance. However, BMI was not associated with prognosis.

CONCLUSION: Serum testosterone level, but not obesity, is a prognostic factor for outcome including survival after getting castration-resistant prostate cancer in men with metastatic prostate cancer having undergone primary ADT.

 

[Michael Scally MD]

Lavallee LT, Binette A, Witiuk K, et al. Reducing the Harm of Prostate Cancer Screening: Repeated Prostate-Specific Antigen Testing. Mayo Clinic Proceedings. http://www.mayoclinicproceedings.org/article/S0025-6196(15)00683-7/fulltext

Objective - To determine if repeating a prostate-specific antigen (PSA) test in men with an elevated PSA level is associated with a decreased risk of prostate biopsy and cancer diagnosis.

Patients and Methods - A cohort of patients referred to the Ottawa Regional Prostate Cancer Assessment Clinic from April 1, 2008, through May 31, 2013, who had referral PSA levels between 4 and 10 ng/mL were included in the study. Univariate and multivariate associations between a normal result on repeated PSA testing and the risk of prostate biopsy, cancer diagnosis, and Gleason score of 7 or higher were examined.

Results - The study cohort included 1268 patients. Repeated PSA test results were normal in 315 patients (24.8%). Men with normal results on repeated PSA testing were younger (mean ± SD age, 61.5±8.2 years vs 65.2±8.2 years; P<.001) and had lower referral PSA levels (mean ± SD, 5.5±1.4 ng/mL vs 6.6±1.5 ng/mL; P<.001) than men with an abnormal repeated PSA result. In multivariate analysis, men with normal results on repeated PSA testing were less likely to undergo prostate biopsy (relative risk [RR], 0.42; 95% CI, 0.34-0.50) and were at lower risk for cancer diagnosis (RR, 0.22; 95% CI, 0.14-0.34) and Gleason score of 7 or higher (RR, 0.16; 95% CI, 0.08-0.34) compared with men who had an abnormal repeated PSA test result.

Conclusion - Routinely repeating a PSA test in patients with an elevated PSA level is independently associated with decreased risk of prostate biopsy and prostate cancer diagnosis. Men with an elevated PSA level should be given a repeated PSA test before proceeding to biopsy.

 

[Michael Scally MD]

Wilt TJ, Dahm P. PSA Screening for Prostate Cancer: Why Saying No is a High-Value Health Care Choice. J Natl Compr Canc Netw 2015;13(12):1566-74. PSA Screening for Prostate Cancer: Why Saying No is a High-Value Health Care Choice

Enthusiasm for cancer screening and treatment of screen-detected cancer has led to widespread prostate-specific antigen (PSA) screening, a marked increase in prostate cancer incidence, and high use of surgical, radiation, and androgen deprivation treatment for screen-detected disease.

This has occurred in advance of a full understanding of the clinical and financial tradeoffs.

Although questions remain whether lifetime benefits outweigh harms and costs, data indicate that this balance is not favorable through at least 15 years.

This article outlines a conceptual framework for determining the value of screening strategies according to screening and treatment intensity.

We describe 4 main cancer screening goals and examine whether PSA screening and treatment achieve these goals and thus provide high-value care.

Available evidence demonstrates that PSA screening provides at best a small reduction in prostate cancer mortality, and no reduction in all-cause mortality.

High-intensity PSA screening and treatment currently practiced in the United States result in substantial harms and large health care expenditures-it is low-value care.

The health importance of prostate cancer and the financial costs to patients and society require improved detection and treatment strategies that produce greater value to patients.

We propose lower-intensity, higher-value options.

However, until evidence supports a higher-value alternative to current PSA screening strategies, physicians should recommend against PSA screening, policymakers should encourage reduced screening, and most men should say no to the PSA test.

 

[MR10X]

Whats your take on this not doing PSA.....i had a PSA done in my 50's and it was normal,i had it done again at 65 and my PSA was 11.4.after a biopsy i was diagnosed with high grade cancer.

 

[Michael Scally MD]

Prostate Cancer: 4 Big Questions
Prostate cancer: 4 big questions : Nature : Nature Publishing Group



Screening: Diagnostic Dilemma
http://www.nature.com/nature/journal/v528/n7582_supp/full/528S120a.html

 

[Xlgx]

Read about grape seed extract as the only truly tested supp with statistical back up supporting prostrate cancer benefits.

 

[MR10X]

i used Tren made with grape seed oil and it didnt help....i got prostrate cancer

 

[Xlgx]

i used Tren made with grape seed oil and it didnt help....i got prostrate cancer

Naturally...

 

[Michael Scally MD]

[No] Relationship between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer

This large secondary analysis of the prostate component of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) generated a lot of media attention when it was released earlier in this year.

This focus, in turn, led balding male patients to come into my office (and I suspect into yours), worrying about their risk of prostate cancer.

When I see large secondary epidemiology studies of this type, I always approach them with a healthy degree of skepticism. In this case it is probably justified.

This study classifies men into 5 groups in worsening degree of baldness “severity,” ie no baldness, frontal baldness only, frontal and mild vertex baldness, frontal and moderate vertex baldness, and frontal and severe vertex baldness.

The study failed to show any association between baldness (regardless of type) and overall risk of incident prostate cancer in PLCO. However, it revealed a relationship between risk of aggressive prostate cancer and frontal plus moderate vertex baldness only. This relationship was not noted in the more severe form of baldness, where the presumed etiology of the association (changes in endogenous hormone levels) would be more pronounced.

This outcome is a red flag to me. If this finding were real, I would expect to see some sort of trend. However, none is there. The authors attribute this lack of trend to limitations in study design but I am inclined to blame a statistically spurious positive finding in the moderate vertex baldness group.

Therefore, you can tell your balding patients to rest easy when it comes to their hairline and prostate cancer (although you may want to remind them to use sunscreen or wear a hat if they are going to be out in the sun).

Penson DF. Re: Relationship between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. J Urol 2015;194(4):990-1. http://www.jurology.com/article/S0022-5347(15)04351-7/fulltext

 

[Michael Scally MD]

Kaplan AL, Hu JC, Morgentaler A, Mulhall JP, Schulman CC, Montorsi F. Testosterone Therapy in Men With Prostate Cancer. European Urology. Elsevier: Article Locator

Context - The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer.

Objective - To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer.

Evidence acquisition - We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer.

Evidence synthesis - The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events.

Conclusions - An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life—and the ability of testosterone therapy to mitigate these effects—has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency.

Patient summary - In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.

 

[Michael Scally MD]

No link to the study. Rider published an abstract earlier this year. http://www.aua2015.org/abstracts/abstractprint.cfm?id=PD6-07


New Study: One Orgasm A Day Could Reduce Prostate Cancer Risk
New study: One orgasm a day could reduce prostate cancer risk

According to a new study, one orgasm a day could reduce a man's risk for prostate cancer.

Researchers claim that while an orgasm provides pleasure during sex, it may also reduce the risk for prostate cancer. It also provides a number of health benefits such as a boost in your immunity, better sleep, and can even protect against heart disease.

…

The study was carried out by scientists at the Harvard Medical School and Brigham and Women Hospital. What they found was that if a male ejaculates at least once a day, he likelihood of developing prostate cancer are very low.

The study data showed that the participants who ejaculated more than 21 times a month were at a 22 percent lower risk of getting the disease.

As for how men achieved ejaculation, it is not a requirement to have a sex partner. Whether it be sexual intercourse, nocturnal emission, or masturbation, all are beneficial.

 

[Michael Scally MD]

Low Serum Testosterone Predicts Upgrading and Upstaging Of Prostate Cancer after Radical Prostatectomy

Often, pathological Gleason Score (GS) and stage of prostate cancer (PCa) were inconsistent with biopsy GS and clinical stage. However, there were no widely accepted methods predicting upgrading and upstaging PCa.

In our study, we investigated the association between serum testosterone and upgrading or upstaging of PCa after radical prostatectomy (RP). We enrolled 167 patients with PCa with biopsy GS </=6, clinical stage </=T2c, and prostate-specific antigen (PSA) <10 ng ml-1 from April 2009 to April 2015. Data including age, body mass index, preoperative PSA level, comorbidity, clinical presentation, and preoperative serum total testosterone level were collected.

Upgrading occurred in 62 (37.1%) patients, and upstaging occurred in 73 (43.7%) patients. Preoperative testosterone was lower in the upgrading than nonupgrading group (3.72 vs 4.56, P< 0.01). Patients in the upstaging group had lower preoperative testosterone than those in the nonupstaging group (3.84 vs 4.57, P= 0.01).

In multivariate logistic regression analysis, as both continuous and categorical variables, low serum testosterone was confirmed to be an independent predictor of pathological upgrading (P = 0.01 and P= 0.01) and upstaging (P = 0.01 and P = 0.02) after RP.

We suggest that low serum testosterone (<3 ng ml-1 ) is associated with a high rate of upgrading and upstaging after RP. It is better for surgeons to ensure close monitoring of PSA levels and imaging examination when selecting non-RP treatment, to be cautious in proceeding with nerve-sparing surgery, and to be enthusiastic in performing extended lymph node dissection when selecting RP treatment for patients with low serum testosterone.

Gao Y, Jiang CY, Mao SK, et al. Low serum testosterone predicts upgrading and upstaging of prostate cancer after radical prostatectomy. Asian J Androl. Low serum testosterone predicts upgrading and upstaging of prostate cancer after radical prostatectomy Gao Y, Jiang CY, Mao SK, Cui D, Hao KY, Zhao W, Jiang Q, Ruan Y, Xia SJ, Han BM, - Asian J Androl

 

[Michael Scally MD]

Shoskes DA, Barazani Y, Fareed K, Sabanegh E, Jr. Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy. Int Braz J Urol 2015;41(6):1167-71. http://www.brazjurol.com.br/november_december_2015/Shoskes_1167_1171.pdf

INTRODUCTION: The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy.

MATERIALS AND METHODS: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns.

RESULTS: 96 men were identified. Mean age at biopsy was 63 (range 40-85) and median PSA was 3.78ng/dL (0.5-662).

Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191-341).

There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9).

Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146-792).

Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7).

CONCLUSIONS: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.

 

[Michael Scally MD]

Prostate Cancer In Men Of African Origin

Men of African origin are disproportionately affected by prostate cancer: prostate cancer incidence is highest among men of African origin in the USA, prostate cancer mortality is highest among men of African origin in the Caribbean, and tumour stage and grade at diagnosis are highest among men in sub-Saharan Africa.

Socioeconomic, educational, cultural, and genetic factors, as well as variations in care delivery and treatment selection, contribute to this cancer disparity.

Emerging data on single-nucleotide-polymorphism patterns, epigenetic changes, and variations in fusion-gene products among men of African origin add to the understanding of genetic differences underlying this disease.

On the diagnosis of prostate cancer, when all treatment options are available, men of African origin are more likely to choose radiation therapy or to receive no definitive treatment than white men.

Among men of African origin undergoing surgery, increased rates of biochemical recurrence have been identified.

Understanding differences in the cancer-survivorship experience and quality-of-life outcomes among men of African origin are critical to appropriately counsel patients and improve cultural sensitivity.

Efforts to curtail prostate cancer screening will likely affect men of African origin disproportionately and widen the racial disparity of disease.

McGinley KF, Tay KJ, Moul JW. Prostate cancer in men of African origin. Nat Rev Urol;advance online publication. http://www.nature.com/nrurol/journal/vaop/ncurrent/full/nrurol.2015.298.html