Prostate ...

[Michael Scally MD]

Kim EH, Andriole GL. Prostate-specific antigen-based screening: controversy and guidelines. BMC Med. 2015;13(1):61. http://www.biomedcentral.com/1741-7015/13/61

Although prostate-specific antigen (PSA) screening has improved the detection of prostate cancer, allowing for stage migration to less advanced disease, the precise mortality benefit of early detection is unclear. This is in part due to a discrepancy between the two large randomized controlled trials comparing PSA screening to usual care. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found a survival benefit to screening, while the United States Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial did not. Furthermore, the benefit of immediate surgical intervention for screen-detected prostate cancer is unclear, as the results superficially differ between the two large randomized controlled trials comparing prostatectomy to observation. The Prostate Cancer Intervention Versus Observation Trial (PIVOT) found no survival benefit for prostatectomy in PSA screened U.S. men, while the Scandinavian Prostate Cancer Group Study Number Four (SPCG-4) found a survival benefit for prostatectomy in clinically diagnosed prostate cancer. As a result of the controversy surrounding PSA screening and subsequent prostate cancer treatment, guidelines vary widely by organization.

 

[Michael Scally MD]

Carlsson S, Vickers A. Spotlight on prostate cancer: the latest evidence and current controversies. BMC Med. 2015;13(1):60. http://www.biomedcentral.com/1741-7015/13/60

Recent decades have seen dramatic changes in the management of prostate cancer based on novel research findings.

Prostate-specific antigen (PSA) screening has been introduced, and then recently modified to include new strategies and biomarkers. Management of advanced disease has been transformed by the rapid introduction of new agents.

We have moved from a "one-size-fits-all" approach in prostate cancer management to multidisciplinary strategies tailored to the individual patient and his specific cancer.

This editorial marks the launch of the article collection Spotlight on prostate cancer (http://www.biomedcentral.com/bmcmed/series/SPR), and here, guest editors Sigrid Carlsson and Andrew Vickers give an overview of the past, present, and future of prostate cancer research and management.

 

[Michael Scally MD]

Kamada S, Sakamoto S, Ando K, Muroi A, Fuse M, et al. Nadir Testosterone after Long-Term Follow-Up Predicts Prognosis of Prostate Cancer Patients Treated With Combined Androgen Blockade. J Urol. http://www.jurology.com/article/S0022-5347(15)03695-2/abstract

PURPOSE: To examine the clinical significance of long-term serum testosterone (TST) monitoring for predicting the prognosis of prostate cancer patients treated with combined androgen blockade (CAB).

MATERIALS AND METHODS: 225 patients who underwent CAB as first-line therapy for prostate cancer were retrospectively analyzed. The prognostic values of serum TST levels and other clinical factors were evaluated with respect to PSA progression-free survival (PFS) and overall survival (OS).

RESULTS: The patients' median age was 73.0 years. The median PSA was 42.6 ng/mL. The median follow-up was 45.8 months.

No variable associated with TST was predictive of PFS. With regard to OS, on univariate analysis, nadir TSTs<16 (p = 0.0190), < 20 (p = 0.0020) and < 32 (p = 0.0146) ng/dL were significant together with other clinical factors. In contrast, nadir TSTs < 8 and < 12 ng/dL were not significant.

Multivariate analysis showed that nadir TST < 20 ng/dL was the significant prognostic factor (p = 0.0048). In addition, time to nadir TST was about 1 year (11.3 months); the patients were divided into rapid type and slow type, based on time to TST < 20 ng/dL before and after six months, respectively.

No significant difference in OS was observed between the two types. The present results suggest that the critical factor for prognosis was not a rapid decrease, but whether nadir TST level achieved < 20 ng/dL.

CONCLUSIONS: Nadir TST 20 ng/dL was the most significant cut-off level for OS in Japanese prostate cancer patients treated with CAB.

 

[Michael Scally MD]

Declining T Levels Provide Increased Opportunity For Mutagenesis In Prostate Stem Cells
http://www.abstractsonline.com/Plan...1e3&mKey=19573a54-ae8f-4e00-9c23-bd6d62268424

Because both normal prostate development and the growth of prostate cancers depend on androgen-mediated activation of androgen receptor (AR) signaling, it is reasonable to hypothesize that androgens and AR signaling play a role in prostate tumor initiation as well; however, little is known about androgens and AR in this process.

We hypothesize that the decline in androgen production that occurs naturally with age contributes directly to tumorigenesis. Previously, we showed that low serum testosterone (T) causes changes in the expression of genes in the androgen/AR signaling axis which allows the prostate tissue to sustain functional androgen levels in rodents. These changes may contribute to prostate tumorigenesis.

There is ongoing debate concerning the cell of origin for prostate cancer, but most evidence would suggest that it can arise from stem cells or cells with stem-like features. Here, we used a murine model to manipulate serum androgen levels to assess the changes in prostate stem-like cells in response to low serum T and to investigate the potential mechanisms by which androgens and AR contribute to prostate tumorigenesis.

Using flow cytometry, we observed that chronic exposure to low T causes a consistent expansion of prostate stem-like cell populations, including Lin-/CD133+/CD117+ cells (from 0.23% to 0.33%), Lin-/CD49fHigh/Trop2+ cells (from 6.47% to 8.42%) and intermediate CK5+/CK8+ cells (from 0.43% to 1.26%).

Using an in vitro sphere forming assay, we found that stem-like cells isolated from low T treated animals had an increased ability to form spheres, suggesting that low T increases self-renewal capacity.

We are currently testing the ability of low T to increase self-renewal capacity in rodent models. Using qPCR, we found that low T causes changes in the expression of genes in the androgen/AR signaling pathway as well as in the oxidative stress response in stem-like cells. We are currently using RNA-seq to understand on a global scale the changes that chronic low T exposure causes in these stem-like cells.

Our studies suggest that chronic exposure to low T, as is the case in older men, could provide a greater opportunity for damage to cells that can become cancer initiating cells.

 

[MR10X]

Just got back from my Oncologist for my 6 month PSA.Its been 2 years since my last radiation treatments and its the lowest yet. My PSA 1 year after treatments was 0.60 my next PSA 6 months later was 0.40,and my latest PSA today was 0.30. This was after a cycle of 150mg test and 150 mg EQ for 8 weeks......Also my TT test done at the same time of the PSA it was 713 )348-1197)this was after PCT done in December.

 

[Michael Scally MD]

Zhou CK, Littman AJ, Levine PH, Hoffman HJ, Cleary SD, et al. Male pattern baldness in relation to prostate cancer risks: an analysis in the VITamins and lifestyle (VITAL) cohort study. Prostate. 2015;75(4):415-23. http://onlinelibrary.wiley.com/doi/10.1002/pros.22927/abstract

BACKGROUND: Male pattern baldness and prostate cancer may share common pathophysiological mechanisms in terms of advancing age, heritability, and endogenous hormones. Results from previous epidemiologic studies are inconsistent. Therefore, we investigated the association of prostate cancer risks with male pattern baldness at age 30 years, age 45 years, and baseline (median age = 60.5 years) in the VITamins And Lifestyle (VITAL) cohort study.

METHODS: We included 32,583 men who were aged 50-76 years and without prior cancer diagnosis (excluding non-melanoma skin cancer) at the start of follow-up. First primary incident prostate cancers were ascertained via linkage to the western Washington Surveillance, Epidemiology, and End Results (SEER) program. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regressions with adjustment for potential confounders.

RESULTS: During follow-up (median = 9 years), 2,306 incident prostate cancers were diagnosed. Male pattern baldness at age 30 years, age 45 years, and baseline were not statistically significantly associated with overall or subtypes of prostate cancer.

CONCLUSION: This study did not provide support for the hypothesis that male pattern baldness may be a marker for subsequent prostate cancer. Previous evidence indicates that a distinct class of frontal with vertex balding may be associated with increased risk of aggressive prostate cancer, but all such balding classes were captured as a single exposure category by the VITAL cohort questionnaire.


Zhou CK, Pfeiffer RM, Cleary SD, Hoffman HJ, Levine PH, et al. 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 Clin Oncol. 2015;33(5):419-25. http://jco.ascopubs.org/content/33/5/419.long

PURPOSE: Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort-the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

METHODS: We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric.

RESULTS: During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score >/= 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer.

CONCLUSION: Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms.

 

[Michael Scally MD]

Peskoe SB, Joshu CE, Rohrmann S, McGlynn KA, Nyante SJ, et al. Circulating total testosterone and PSA concentrations in a nationally representative sample of men without a diagnosis of prostate cancer. Prostate. http://onlinelibrary.wiley.com/doi/10.1002/pros.22998/abstract

BACKGROUND: The association between serum sex steroid hormones and PSA in a general population has not been described.

METHODS: Included were 378 men aged 40-85 years who participated in the National Health and Nutrition Examination Survey in 2001-2004, who did not have a prostate cancer diagnosis, and had not had a recent biopsy, rectal examination, cystoscopy, or prostate infection or inflammation. Serum total PSA, total testosterone, androstanediol glucuronide (3alpha-diol-G), estradiol, and sex hormone binding globulin (SHBG) concentrations were previously measured. Free testosterone was estimated by mass action. We applied sampling weights and calculated geometric mean PSA concentration by hormone quintiles adjusting for age and race/ethnicity, and also for body mass index, waist circumference, smoking, diabetes, and mutually for hormones. We estimated the OR of PSA >/=2.5 ng/ml per hormone quintile using logistic regression.

RESULTS: Geometric mean PSA increased across testosterone quintiles after age and race/ethnicity (Q1: 0.80, Q5: 1.14 ng/ml; P-trend = 0.002) and multivariable (Q1: 0.79, Q5: 1.16 ng/ml; P-trend = 0.02) adjustment; patterns were similar for free testosterone and 3alpha-diol-G. SHBG was inversely associated with PSA only after multivariable adjustment (Q1: 1.32, Q5: 0.82 nmol/L; P-trend = 0.01). Estradiol and PSA were not associated. The OR of PSA >/=2.5 ng/ml was 1.54 (95%CI 1.18-2.01) per testosterone quintile after age and race/ethnicity adjustment, and 1.78 (95%CI 1.16-2.73) after multivariable adjustment.

CONCLUSIONS: In this nationally representative sample, men with higher testosterone had higher PSA even after taking into account other hormones and modifiable factors. Men with higher SHBG had lower PSA, but only after multivariable adjustment.

 

[Michael Scally MD]

Castillo OA, Lopez-Fontana G, Vidal-Mora I, Lopez Laur JD. [Testosterone replacement therapy and prostate cancer: the downfall of a paradigm?]. Medwave. 2015;15(3):e6115. http://www.ncbi.nlm.nih.gov/pubmed/25919660

For six decades, it has been a part of the conventional medical wisdom that higher levels of testosterone increase the risk of prostate cancer.

This belief is mostly derived from the well-documented regression of prostate cancer after surgical or pharmacological castration.

However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer.

Moreover, men with hypogonadism have substantial rates of prostate cancer in prostatic biopsies, suggesting that low testosterone has no protective effect against the development of prostate cancer.

Moreover, prostate cancer rate is higher in elderly patients when hormonal levels are low.

These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

 

[Deadballs]

If your urine stream is ultra powerful is it a reasonable indicator through life that you probably haven't got a prostate problem? I'm not saying don't get check ups, I'm saying as an extra indicator it could be of benefit? Or could you get prostate cancer with no inflammation of enlargement of the prostate whatsoever?

 

[MR10X]

After ADT and treatment

09/04/2013
TT 137 (348-1197)
PSA 0.60

06/04/2014
TT 493 (348-1197)
PSA 0.40

04/03/2015
TT 713 (348-1197)
PSA 0.30

 

[MR10X]

I never had Prostrate enlargement or urination problems but had high grade cancer......

 

[Deadballs]

I never had Prostrate enlargement or urination problems but had high grade cancer......

Well that's valuable info, thanks!

 

[Michael Scally MD]

Regis L, Planas J, Celma A, de Torres IM, Ferrer R, et al. Behavior of total and free serum testosterone as a predictor for the risk of prostate cancer and its aggressiveness. Actas Urol Esp. https://www.sciencedirect.com/science/article/pii/S0210480615001217

CONTEXT: Serum testosterone is mostly bound to the sex hormone-binding globulin and albumin. A small metabolically active part is present in the form of free testosterone (FT). The relationship between serum total testosterone (TT) levels and prostate carcinogenesis is debated. Our hypothesis is that the serum FT concentration is more closely associated with the risk of prostate cancer (PC) and its aggressiveness than TT.

OBJECTIVE: To analyze the scientific evidence that relates serum TT and/or FT levels with the diagnosis of PC and its aggressiveness.

ACQUISITION OF EVIDENCE: A systematic review was conducted in PubMed up to January 2015 using the following mesh terms: prostate cancer, sex hormone, androgen, testosterone and free testosterone.

SYNTHESIS OF THE EVIDENCE: We found 460 publications, 124 of which were reviewed to analyze the evidence. The relationship between serum TT levels and the diagnosis of PC and its aggressiveness is highly heterogeneous. The variability in the design of the studies, the quantification methods and other variables could explain this heterogeneity. In a number of studies that evaluated the estimated or measured FT, the evidence remains equally conflicting.

CONCLUSIONS: Based on the current evidence, we cannot recommend the measurement of serum TT and/or TL levels for the diagnosis of PC or for assessing its aggressiveness.

 

[Michael Scally MD]

Chau CH, Price DK, Till C, Goodman PJ, Chen X, et al. Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial. PLoS One. 2015;10(5):e0126672. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126672

OBJECTIVE: In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.

METHODS: Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.

RESULTS AND CONCLUSIONS: Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.

 

[Michael Scally MD]

Chen R, Cui J, Wang Q, Li P, Liu X, et al. Antiproliferative effects of anastrozole on MCF7 human breast cancer cells in vitro are significantly enhanced by combined treatment with testosterone undecanoate. Mol Med Rep. 2015;12(1):769-75. http://www.spandidos-publications.com/mmr/12/1/769

The present study aimed to assess the effects of aromatase inhibitor anastrozole and testosterone undecanoate, separately and in combination, on proliferation and apoptosis in MCF7 human breast cancer cells cultured in vitro.

The effects of various concentrations of these drugs on the proliferation of MCF7 cells were evaluated by CCK8 assay, the levels of cell apoptosis were evaluated by flow cytometry with AnnexinV/propidium iodide staining and androgen receptor (AR) protein expression was determined by western blot analysis.

The results of the CCK8 assay indicated that greater ANTIPROLIFERATIVE activity was detected in the MCF7 cells in the combined treatment groups, compared with those treated with anastrozole or testosterone undecanoate alone.

Flow cytometric analysis of apoptosis revealed that treatment with a combination of the two drugs generated a higher percentage of apoptotic cells, particularly when the two drugs were applied for 48 h, compared with single drug treatment.

Western blot analysis revealed a significant decrease in AR protein expression in the combined treatment groups compared with MCF7 cells treated with single drugs.

The results of the present study provided evidence supporting the potential of a combination of anastrozole and testosterone undecanoate as a novel therapeutic strategy for the treatment of breast cancer.

Furthermore, it was demonstrated that the antiproliferative effects of anastrozole were significantly enhanced by combined treatment with testosterone undecanoate via the AR signaling pathway.

 

[Michael Scally MD]

Park E, Kim EK, Kim M, Ha JM, Kim YW, et al. Androgen Receptor-dependent Expression of Low-density Lipoprotein Receptor-related Protein 6 is Necessary for Prostate Cancer Cell Proliferation. Korean J Physiol Pharmacol. 2015;19(3):235-40. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422963/

Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell proliferation.

Here, we showed that proliferation of hormone-sensitive prostate cancer cells such as LNCaP was significantly enhanced by testosterone stimulation whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not respond to testosterone stimulation.

Blocking of AR using bicalutamide abolished testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR blocked testosterone-induced proliferation of LNCaP cells.

Basal expression of low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP cells whereas stimulation of testosterone did not affect the expression of LRP6.

However, expression of LRP6 in LNCaP cells was increased by testosterone stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced proliferation of LNCaP cells.

Given these results, we suggest that androgen-dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate cancer cell proliferation.

 

[Michael Scally MD]

Hwang EC, Yu SH, Jo YH, Jung SI, Kang TW, et al. Effect of serum testosterone and percent tumor volume on extra-prostatic extension and biochemical recurrence after laparoscopic radical prostatectomy. Asian J Androl. http://www.ajandrology.com/preprintarticle.asp?id=154317

Several studies have revealed that the preoperative serum testosterone and percent tumor volume (PTV) predict extra-prostatic extension (EPE) and biochemical recurrence (BCR) after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy (LRP). We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen (PSA) >0.2 ng ml-1 . The threshold for serum total testosterone was 3.0 ng ml-1 . Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone (<3.0 ng ml-1 ) was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone (<3.0 ng ml-1 , adjusted OR, 8.52; 95% CI, 5.04-14.4, P= 0.001) predicted EPE and PTV (adjusted OR, 1.02; 95% CI, 1.01-1.05, P= 0.046) predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.

 

[Michael Scally MD]

Endogenous and Exogenous Testosterone and the Risk of Prostate Cancer and Prostate Specific Antigen
http://www.aua2015.org/abstracts/abstractprint.cfm?id=MP4-09

Introduction and Objectives - To review and quantify the association between endogenous and exogenous testosterone and prostate specific antigen (PSA) and prostate cancer.

Methods - Literature searches were performed following the PRISMA guidelines. Prospective cohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo controlled randomised trial studies of testosterone replacement therapy that reported data on PSA and prostate cancer cases were retained.

Meta-analyses were carried out using a random effects model with tests for statistical significance, publication bias and heterogeneity.

Results - Twenty estimates derived from 18 studies, based on a total of 5,091 patients with prostate cancer and 11,930 controls, were included in a meta-analysis which produced a summary relative risk (SRR) of prostate cancer for the highest vs. lowest quantile of serum testosterone of SRR=0.98 (95% CI (0.88, 1.09)).

Based on data from 24 trials, the overall difference in PSA levels following onset of use of testosterone replacement therapy was 0.11 ng/mL (95% CI (-0.23, 0.46)) which was not statistically significant.

When restricting to transdermal testosterone replacement therapy, the overall difference in PSA levels was 0.23 ng/mL (95% CI (-0.53, 0.99)) which, again, is not statistically significant.

The summary relative risk of prostate cancer as an adverse effect from 11 TRT trials was SRR=0.94 (95% CI (0.37; 2.40)), again not statistically significant.

Conclusions - Prostate cancer development appears to be unrelated to endogenous serum testosterone levels.

Testosterone replacement therapy for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development.

The current data are reassuring although care is essential until multiple studies with longer follow-up are available.

 

[Michael Scally MD]

Integrative Clinical Genomics of Advanced Prostate Cancer

Highlights
· A multi-institutional integrative clinical sequencing of mCRPC
· Approximately 90% of mCRPC harbor clinically actionable molecular alterations
· mCRPC harbors genomic alterations in PIK3CA/B, RSPO, RAF, APC, β-catenin, and ZBTB1.
· 23% of mCRPC harbor DNA repair pathway aberrations, and 8% harbor germline findings

Robinson D, Van-Allen EM, Wu Y-M, Schultz N, Lonigro RJ, et al. Integrative Clinical Genomics of Advanced Prostate Cancer. Cell. 2015;161(5):1215-28. http://www.cell.com/cell/abstract/S0092-8674(15)00548-6

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals.

Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer.

We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers.

89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations.

This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

 

[Michael Scally MD]

Kantor ED, Lipworth L, Fowke JH, Giovannucci EL, Mucci LA, et al. Statin use and risk of prostate cancer: Results from the Southern Community Cohort Study. Prostate. http://onlinelibrary.wiley.com/doi/10.1002/pros.23019/abstract

BACKGROUND: Epidemiologic studies suggest that statin use may be inversely associated with risk of prostate cancer, but prior studies have focused predominantly on non-Hispanic white populations.

METHODS: We evaluated the association between statin use and prostate cancer risk in the Southern Community Cohort Study (SCCS). Study participants were 32,091 men aged 40-79 at baseline, 67% of whom were non-Hispanic black. Between study enrollment (2002-2009) and December 31, 2010, 570 prostate cancer cases were diagnosed, including 324 low-grade cancers (Gleason score <7 or Gleason pattern 3 + 4) and 107 high-grade cancers (Gleason score >7 or Gleason pattern 4 + 3). Analyses of overall prostate cancer were conducted using Cox regression and analyses of grade-specific cancer were conducted using competing risks models.

RESULTS: Ten percent of non-Hispanic black men and 22% of non-Hispanic white men reported use of statins at study enrollment. As compared to non-use, statin use was associated with a non-significant 14% lower risk of prostate cancer in multivariable models (Hazard Ratio

---

:0.86; 95% Confidence Interval [CI]: 0.63-1.18). This association was stronger for high-grade cancer (HR: 0.62; 95%CI: 0.30, 1.28) than low-grade cancer (HR:0.98; 95%CI: 0.65-1.48). Results were similar by race/ethnicity (p-interaction: 0.41) and did not vary by history of prostate-specific antigen [PSA] screening (p-interaction: 0.65).

CONCLUSIONS: Results suggest no strong association between statin use and prostate cancer risk overall, and further suggest that if a modest protective effect does exist, it does not vary by race/ethnicity and may be restricted to high-grade tumors, although power to detect differences by subgroup was limited.