Prostate ...

Discussion in 'Men's Health Forum' started by Michael Scally MD, Sep 22, 2010.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Association of Statin Use with Risk of Gleason Score-Specific Prostate Cancer

    Background Conflicting evidence suggests that statins act chemopreventively against prostate cancer (PCa). Whether the association of statin use with PCa risk is Gleason score-dependent, time-, dose-respondent is not well studied.

    Methods We conducted a cohort study at a tertiary hospital in the Southeastern US using longitudinal data of electronic medical records (EMR) from 1994 to 2016. Only cancer-free men aged >18 years at baseline with follow-up time of ≥12 months were included. Time-dependent Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).

    Results Among 13 065 men, 2976 were diagnosed with PCa over median follow-up of 6.6 years. Statin use was associated with lower risk of both Gleason low- (score <7: aHR, 0.85; 95% CI, 0.74-0.96) and high-grade PCa (score ≥7: aHR, 0.54; 95% CI, 0.42-0.69).

    The protective association was observed only when statins had been used for a relatively longer duration (≥11 months) or higher dose (≥121 defined daily doses), and were more pronounced for PCa of higher Gleason score (<7: aHR, 0.85, 95% CI, 0.74-0.96; 7 [3 + 4]: aHR, 0.62, 95% CI, 0.43-0.90; 7 [4 + 3]: aHR, 0.49, 95% CI, 0.29-0.82; 8: aHR, 0.60, 95% CI, 0.37-0.96; 9-10: aHR, 0.24, 95% CI, 0.11-0.54). Lipophilic statins (aHR, 0.83; 95% CI, 0.72-0.95) might be more protective than hydrophilic statins (aHR, 0.91, 95% CI, 0.63-1.33) against PCa.

    Conclusion Statin use might be associated with reduced PCa risk only when used for a relatively longer duration, and the risk reduction was higher for PCa of higher Gleason score.

    Wang K, Gerke TA, Chen X, Prosperi M. Association of statin use with risk of Gleason score-specific prostate cancer: A hospital-based cohort study. Cancer Medicine 2019;0. Error - Cookies Turned Off


     
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Pursuing an Elusive Prostate Carcinoma: A Case Report Involving Multiparametric MR and CT-Guided Biopsy

    Prostate cancer is usually diagnosed when elevated PSA levels lead to a TRUS biopsy. We present a case in which there were several negative biopsies and a rising PSA.

    This led to a multiparametric MR (mpMRI) which demonstrated a large mass which originated in the anterior transition zone and had extended through the anterior fibromuscular stroma and prostate capsule with a significant extra-prostatic component.

    The mass was successfully approached anteriorly with a CT-guided biopsy. The patient was subsequently successfully treated with radiotherapy utilizing MR in the planning process.

    This case report summarizes the utility of mpMRI in this clinical setting. For patients with high suspicion of prostate malignancy despite prior negative biopsies, it can identify tumor in locations not amenable to TRUS biopsy. It also is critical for accurate radiation treatment planning, allowing for increased confidence in tumor targeting as well as sparing sensitive normal tissue.

    Olson DO, Baisden JM, Groten DL, Talug C. Pursuing an Elusive Prostate Carcinoma: A Case Report Involving Multiparametric MR and CT-Guided Biopsy. Case reports in oncology 2019;12:737-41. Pursuing an Elusive Prostate Carcinoma: A Case Report Involving Multiparametric MR and CT-Guided Biopsy
     
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Non-nuclear AR Signaling in Prostate Cancer

    Despite the key role played by androgen receptor (AR) in tumor cell aggressiveness and prostate cancer (PCa) progression, its function in the tumor microenvironment (TME) is still controversial. Increasing studies highlight the crucial role played by TME modulation in treatment outcome and tumor cell spreading.

    In this context, targeting specific constituents of the TME could be considered an alternative approach to classic treatments directed against cancer cells. Currently, androgen deprivation therapy (ADT) is a routinely adopted strategy in the management of PCa, with initial success, and consecutive fail.

    A possible justification to this is the fact that ADT aims to target all the transcription/translation-related activities of AR, which are typical of tumor epithelial cells. Less is still known about side effects of ADT on TME.

    Cancer Associated Fibroblasts (CAFs), for example, express a classic AR, mostly confined in the extra-nuclear portion of the cell. In CAFs ADT exerts a plethora of non-transcriptional effects, depending by the protein partner linked to AR, leading to cell migration, proliferation, and differentiation.

    In recent years, substantial progress in the structure-function relationships of AR, identification of its binding partners and function of protein complexes including AR have improved our knowledge of its signaling axis. Important AR non-genomic effects and lots of its cytoplasmatic binding partners have been described, pointing out a fine control of AR non-genomic pathways.

    Accordingly, new AR inhibitors have been designed and are currently under investigation. Prompt development of new approaches to target AR or block recruitment of its signaling effectors, or co-activators, is urgently needed. The present review takes an in-depth look at current literature, furnishing an exhaustive state-of-the-art overview of the non-genomic role of AR in PCa, with particular emphasis on its involvement in TME biology.

    Zamagni A, Cortesi M, Zanoni M, Tesei A. Non-nuclear AR Signaling in Prostate Cancer. Frontiers in chemistry 2019;7:651. Non-nuclear AR Signaling in Prostate Cancer
     
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Aging, Fat Mass, and Prostate Cancer: Is It the Time to Reconsider testosterone?

    The rising epidemic of obesity and metabolic syndrome leads to an ever-growing attention by the public health systems. It is well known that these conditions are associated with the development of metabolic and cardiovascular diseases, such as type 2 diabetes (T2D), heart failure and stroke, requiring chronic therapies, hospitalizations and invasive procedures.

    However, the burden of obesity is related not only with cardio-metabolic complications but also with the risk of developing some forms of cancer. In fact, obesity and metabolic syndrome are now recognized as risk factors for several types of cancers, … with high BMI being associated with higher cancer invasiveness and mortality.



    In the light of the increasing demand for testosterone replacement therapy in obesity, metabolic syndrome and aging, which can no longer be neglected, the overall risk profile of hormonal replacement therapy has to be reconsidered, properly balancing the negative and the beneficial effects.

    Future studies have to be provided to confirm the anti-inflammatory, well-aging, and anti-neoplastic potential of testosterone, together with its long-term complications. Furthermore, considering the lack of a standardized approach in clinical practice for testosterone measurement in patients diagnosed with PCa, future works could also assess how many clinicians evaluate testosterone at the diagnosis, and how often the determination of testosterone plasma levels should be performed over time.

    Di Vincenzo A, El Hadi H, Vettor R, Rossato M. Aging, fat mass, and prostate cancer: is it the time to reconsider testosterone? Aging Clinical and Experimental Research 2019. https://doi.org/10.1007/s40520-019-01372-7
     

    Attached Files:

  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Sex Hormones and Prostate Cancer

    The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths.

    Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease.

    Although it was assumed that the cancer became androgen independent during this transition, studies over the last two decades have shown that these tumors evade treatment via mechanisms that augment acquisition of androgens from circulating precursors, increase sensitivity to androgens and androgen precursors, bypass the androgen receptor, or a combination of these mechanisms.

    This review summarizes the history of prostate cancer research leading to the contemporary view of androgen dependence for prostate cancers and the current treatment approaches based on this modern paradigm.

    Auchus RJ, Sharifi N. Sex Hormones and Prostate Cancer. Annual review of medicine 2019. https://www.annualreviews.org/doi/10.1146/annurev-med-051418-060357
     

    Attached Files:

  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Association of Long-Term Dynamics in Circulating testosterone with Serum PSA in Prostate Cancer-Free Men with Initial-PSA < 4 ng/mL

    We previously reported that an accelerated decline in circulating testosterone level is associated with a higher risk of prostate cancer (PCa). This study is to examine whether testosterone change rate is related to serum prostate-specific antigen (PSA) concentration among PCa-free men.

    Longitudinal data were derived from electronic medical records at a tertiary hospital in the Southeastern USA. PCa-free men with initial-PSA < 4 ng/mL and >/= 2 testosterone measurements were included (n = 632). Three PSA measures (peak, the most recent, and average PSA) during the study period (from first testosterone measurement to the most recent hospital visit) were examined using multivariable-adjusted geometric means and were compared across quintiles of testosterone change rate (ng/dL/month) and current testosterone level (cross-sectional).

    Mean (standard deviation, SD) age at baseline was 59.3 (10.5) years; mean study period was 93.0 (55.3) months. After adjusting for covariates including baseline testosterone, the three PSA measures all significantly increased across quintile of testosterone change rate from increase to decline (peak PSA: quint 1 = 1.09, quint 5 = 1.41; the most recent PSA: quint 1 = 0.85, quint 5 = 1.00; average PSA: quint 1 = 0.89, quint 5 = 1.02; all Ptrend < 0.001). But current testosterone level was not associated with PSA levels.

    Stratified analyses indicated men with higher adiposity (body mass index > 24.1 kg/m(2)) or lower baseline testosterone (</= 296 ng/dL) were more sensitive to testosterone change in regard to PSA. Among PCa-free men, accelerated testosterone decline might correlate with higher serum PSA concentration. It will help to elucidate the mechanisms relating aging-accompanying testosterone dynamics to prostate carcinogenesis.

    Wang K, Chen X, Cheng TD, Qiu P, Bird VY, Prosperi M. Association of Long-Term Dynamics in Circulating Testosterone with Serum PSA in Prostate Cancer-Free Men with Initial-PSA < 4 ng/mL. Hormones & cancer 2019. Association of Long-Term Dynamics in Circulating Testosterone with Serum PSA in Prostate Cancer-Free Men with Initial-PSA < 4 ng/mL
     
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy

    BACKGROUND: Previous studies have found an association between androgen deprivation therapy (ADT) and an increased risk of dementia and depression in elderly men. This association remains controversial, and little is known about the effects of ADT in younger men.

    OBJECTIVE: To examine the association between the receipt of ADT and these outcomes in young men aged 40-64 yr presenting with nonmetastatic prostate cancer (PCa).

    DESIGN, SETTING, AND PARTICIPANTS: For this observational study, we identified 9117 men aged 40-64 yr diagnosed with localized PCa between 2007 and 2014, without a pre-existing neurocognitive diagnosis, using the TRICARE military database.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier curves were fitted to compare ADT versus no ADT. We also performed a subgroup analysis in patients undergoing ADT for >/=12 mo. The association between ADT and new-onset dementia or depression was evaluated using inverse-probability-of treatment-weight-adjusted Cox proportional hazards regression analysis.

    RESULTS AND LIMITATIONS: Patients receiving ADT had a significantly higher incidence of depression (30.2 vs 15.8 per 1000 person years) and dementia (17.9 vs 7.5 per 1000 person years). The risk of developing either outcome was higher in the ADT cohort (depression: hazard ratio [HR] 2.07, p < 0.001; dementia: HR 1.70, p = 0.052). Additionally, there was a dose-response relationship between the duration of ADT and either outcome.

    CONCLUSIONS: In our cohort of young men with PCa, the receipt of ADT was associated with an increased risk of developing dementia and depression. Long-term use of ADT was associated with the highest risk of neurocognitive outcomes.

    PATIENT SUMMARY: In this study, we looked at the risk of dementia and depression in patients <65 yr of age undergoing androgen deprivation therapy (ADT) for prostate cancer. We found that these patients had a higher risk of dementia and depression than those who did not undergo ADT.

    Tully KH, Nguyen DD, Herzog P, et al. Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy. European urology oncology 2019. https://euoncology.europeanurology.com/article/S2588-9311(19)30129-4/fulltext
     
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    testosterone Therapy in Relation to Prostate Cancer in A US Commercial Insurance Claims Database

    Background: We conducted a study assess whether testosterone therapy (TT) alters prostate cancer risk using a large US commercial insurance research database.

    Methods: From the HealthCore Integrated Research Database (HIRDSM), we selected men aged 30 years or greater who were new users of TT during 2007-2015.

    We selected two comparison groups:
    1) unexposed (matched 10:1);
    2) new users of phosphodiesterase type 5 inhibitor (PDE5i).

    Incident prostate cancer was defined as diagnosis of prostate cancer within four-weeks following prostate biopsy. Propensity scores and inverse probability of treatment weights were used in Poisson regression models to estimate adjusted incidence rates, incidence rate ratios (IRRs) and 95% confidence intervals (CI). Subgroup analyses included stratification by prostate cancer screening, hypogonadism, and follow-up time.

    Results: The adjusted prostate cancer IRR was 0.77 (95%CI: 0.68, 0.86) when comparing TT with the unexposed group and 0.85 (95%CI: 0.79, 0.91) in comparison with the PDE5i group. Inverse associations between TT and prostate cancer were observed in a majority of subgroup analyses, although in both comparisons estimates generally attenuated with increasing time following initial exposure. Amongst TT users, duration of exposure was not associated with prostate cancer.

    Conclusions: Men who received TT did not have a higher rate of prostate cancer compared with the unexposed or PDE5i comparison groups. The inverse association between TT and prostate cancer could be the result of residual confounding, contraindication bias, or undefined biologic effect. Impact: This study suggests that limited TT exposure does not increase risk of prostate cancer in the short-term.

    Cook MB, Beachler DC, Parlett LE, et al. Testosterone therapy in relation to prostate cancer in a US commercial insurance claims database. Cancer Epidemiology Biomarkers & Prevention 2019. Testosterone therapy in relation to prostate cancer in a US commercial insurance claims database
     
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  9. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Should We Even Talk About a PSA?
    Should We Even Talk About a PSA?



    Although the PSA test was not developed to screen asymptomatic men for prostate cancer, primary care physicians were persuaded by expert opinion to use it for nearly two decades in this way before the publication of the only US trial testing its efficacy. That study, and its subsequent reports, found that the test did not decrease prostate cancer deaths and there was clear evidence of harm to the screening group. It has appropriately led to less PSA screening being performed in the United States, ensuring that fewer patients suffer from a needless test.

    In contrast to the USPSTF's current recommendation to discuss the pros and cons of PSA-based screening, the best evidence indicates that routine use of a decision aid does not improve clinical outcomes. My practice, therefore, follows the lead of the AAFP. I do not recommend prostate cancer screening. If patients ask me about it, I tell them, "The PSA test is unlikely to help you and is much more likely to cause harm." If they still want the test, I will order it. These patients, at least, know what they are getting themselves into rather than being stranded with millions of other men on the shores of SDM.
     
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  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Huynh LM, Ahlering TE. Challenging beliefs of testosterone therapy and prostate cancer. Nature Reviews Urology 2019. https://doi.org/10.1038/s41585-019-0253-8

    The relationship between testosterone therapy and prostate cancer continues to challenge historic and current beliefs. A new cohort analysis revealed a ~33% reduction in prostate cancer incidence in men with increased testosterone use. The mechanisms underlying this protective effect are unclear, but these findings challenge current paradigms and warrant further investigation.
     

    Attached Files:

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  11. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Performance and Inter-Observer Variability of Prostate MRI

    Objective: Despite the growing trend to embrace pre-biopsy MRI in the diagnostic pathway for prostate cancer (PC), its performance and inter-observer variability outside high-volume centres remains unknown. This study aims to evaluate sensitivity of and variability between readers of prostate MRI outside specialized units with radical prostatectomy (RP) specimen as the reference standard.

    Materials and methods: Retrospective study comprising a consecutive cohort of all 97 men who underwent MRI and subsequent RP between January 2012 and December 2014 at a private hospital in Sweden. Three readers, blinded to clinical data, reviewed all images (including 11 extra prostate MRI to reduce bias).

    A tumour was considered detected if the overall PI-RADS v2 score was 3–5 and there was an approximate match (same or neighbouring sector) of tumour sector according to a 24 sector system used for both MRI and whole mount sections.

    Results: Detection rate for the index tumour ranged from 67 to 76%, if PI-RADS 3–5 lesions were considered positive and 54–66% if only PI-RADS score 4–5 tumours were included. Detection rate for aggressive tumours (GS ≥ 4 + 3) was higher; 83.1% for PI-RADS 3–5 and 79.2% for PI-RADS 4–5. The agreement between readers showed average κ values of 0.41 for PI-RADS score 3–5 and 0.51 for PI-RADS score 4–5.

    Conclusions: Prostate MRI evidenced a moderate detection rate for clinically significant PC with a rather large variability between readers. Clinics outside specialized units must have knowledge of their performance of prostate MRI before considering omitting biopsies in men with negative MRI.

    Kohestani K, Wallström J, Dehlfors N, et al. Performance and inter-observer variability of prostate MRI (PI-RADS version 2) outside high-volume centres. Scandinavian Journal of Urology 2019:1-8. https://doi.org/10.1080/21681805.2019.1675757
     
  12. SaneDog

    SaneDog Member

    I've been needing some more information on this, thank you for providing.