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

    testosterone Replacement Therapy and the Risk of Prostate Cancer

    The association between the use of testosterone replacement therapy (TRT) and prostate cancer remains uncertain. Thus, we investigated whether TRT is associated with an increased risk of prostate cancer in men with late-onset hypogonadism.

    We used the United Kingdom Clinical Practice Research Datalink to assemble a cohort of 12,779 men newly-diagnosed with hypogonadism between 1 January 1995 and 31 August 2016, with follow-up until 31 August 2017. Exposure to TRT was treated as a time-varying variable and lagged by 1 year to account for cancer latency, with non-use as the reference category. During 58,224 person-years of follow-up, a total of 215 patients were newly-diagnosed with prostate cancer, generating an incidence rate of 3.7 per 1,000 person-years.

    In time-dependent Cox proportional hazards models, use of TRT was not associated with an overall increased risk of prostate cancer (hazard ratio = 0.97; 95% confidence interval: 0.71, 1.32), compared with non-use. Results remained consistent in secondary and sensitivity analyses, as well as in a propensity score-matched cohort analysis that further assessed the impact of residual confounding. Overall, the use of TRT was not associated with an increased risk of prostate cancer in men with late-onset hypogonadism.

    Santella C, Renoux C, Yin H, Yu OHY, Azoulay L. Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men with Late-Onset Hypogonadism. American journal of epidemiology 2019. Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men with Late-Onset Hypogonadism
     
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    When Fat Goes Down, Prostate Cancer Is On The Ropes

    Reprogrammed lipid metabolism and persistent androgen receptor signaling commonly mark aggressive prostate cancer.

    We describe that targeting de-novo lipogenesis deprives prostate cancer cells of substrates and fuel, while inhibiting androgen receptor signaling.

    Our study uncovers the interplay between lipogenesis and androgen receptor and proposes novel combinatorial therapeutic approaches.

    Zadra G, Loda M. When fat goes down, prostate cancer is on the ropes. Molecular & cellular oncology 2019;6:1595308. https://www.tandfonline.com/doi/full/10.1080/23723556.2019.1595308
     

    Attached Files:

  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Holt JD, Gerayli F. Prostate Cancer Screening. Primary care 2019;46:257-63. Prostate Cancer Screening - ScienceDirect

    KEY POINTS

    · The benefits of prostate-specific antigen (PSA) screening in men aged 55 to 69 at average risk for prostate cancer are small: reduced risk for prostate cancer deaths and metastatic disease, but no decrease in overall mortality.

    · To realize the benefits from PSA screening in men at average risk for prostate cancer, PSA thresholds must be low enough that many false positives, many biopsies, and overdiagnosis of indolent cancers will occur.

    · The harms of PSA screening for prostate cancer are significant: anxiety, complications from biopsy, and morbidity from overly aggressive treatment.

    · There is little evidence evaluating benefits of PSA screening in populations at increased risk for prostate cancer, such as men with a positive family history or African American men.

    · Men 70 and older experience less benefit and more harm from PSA screening for prostate cancer. PSA screening is not recommended for them.

    Whether to screen for prostate cancer in aging men is a topic that is fairly well researched, but recommendations are controversial, because the evidence supporting any recommendation is equivocal. The evidence clearly does not support routine screening of all average-risk men, but for men aged 55 to 69 years, either not routinely screening, or engaging each man in shared decision making for his individual preference on screening, is reasonable and consistent with the evidence. Many organizations, including the American Cancer Society, have not yet reassessed their guidelines, in response to the US Preventative Services Task Force revised guideline.
     

    Attached Files:

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  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Negative Predictive Value of Prostate Multi-Parametric Magnetic Resonance Imaging Among Men with Negative Prostate Biopsy and Elevated PSA

    PURPOSE: To estimate the negative predictive value (NPV) of prostate mpMRI in the detection of clinically significant (Gleason >/=7) prostate cancer (csPCa) at long-term follow-up (median 6.7 years, range 2.6-10.7 years), in men with negative pre-MRI biopsy and to assess the diagnostic performance of mpMRI in detecting csPCa over this time.

    MATERIALS AND METHODS: Following Institutional REB-approval, men with prostate mpMRI following a biopsy between 2004-2009 were identified retrospectively from a cancer registry database and MRI reports. The mpMRI sequences comprised T2-weighted and dynamic contrast-enhanced series (2004-2005) with diffusion-weighted imaging 2006 onwards.

    Clinical outcomes were assessed up to July 2015 by review of subsequent pathology results, PSA levels and review of electronic patient records. The primary outcome was csPCa diagnosis by follow-up. We also estimated the sensitivity, specificity, PPV and NPV of all prostate mpMRI during the period.

    RESULTS: 502 mpMRI with a prior biopsy were included. 121 were in men with a prior negative systematic biopsy for cancer (median PSA 9.5; median age 60 years). Of these, 96% (70/73) of men with negative mpMRI remained free of csPCa at median follow-up of 6.7 years (range 2.6-10.7 years). The overall NPV and PPV of mpMRI in the entire cohort regardless of pre-MRI biopsy status was 86% (80-91%) and 54% (52-57%) respectively, in the time period.

    CONCLUSION: Prostate mpMRI has high clinical NPV. In men with pre-MRI negative biopsy and a negative MRI, the risk of developing clinically significant prostate cancer at median 6.7 years is extremely low.

    Lo G, Burton KR, Haider MA, Fleshner N, Finelli A, Ghai S. Negative predictive value of prostate multi-parametric magnetic resonance imaging among men with negative prostate biopsy and elevated PSA - a clinical outcome retrospective cohort study. The Journal of urology 2019:101097ju0000000000000388. American Urological Association
     
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] A Novel Patient Case Report to Show the Successful Termination of Untreatable Androgen-independent Prostate Cancer: Treatment with cabergoline

    INTRODUCTION: testosterone promotes the initial development of androgen-dependent prostate cancer. This is the basis for androgen ablation treatment, which attenuates, but does not terminate, the malignancy. Instead, it leads to prolactin-dependent malignancy; in which patient death generally occurs within 5 years. This report describes the novel treatment of a patient; which terminated androgen-independent prostate cancer.

    RESULTS: Patient "XY" was diagnosed with prostate malignancy and metastases. He received hormonal androgen ablation treatment, chemotherapy, and radiation treatment. He developed androgen-independent prostate cancer; with expected death in 2-3 years. He was treated with cabergoline (dopamine agonist) treatment, which decreased the plasma prolactin 88%; by inhibiting the pituitary production of prolactin. The subsequent PET scan (positron emission tomography) revealed the absence of malignancy; and the CTC (circulating tumor cells) decreased from count=5.4 to count=0.

    DISCUSSION: The cause of androgen-independent malignancy has been unknown, and an effective chemotherapy did not exist. The activities of normal and malignant prostate cells are regulated primarily by testosterone. When testosterone availability diminishes; prolactin regulation is manifested. This is represented when androgen ablation results in the development of prolactin-dependent malignancy. An effective chemotherapy would be targeted to eliminate the plasma prolactin-manifestation of the androgen-independent malignancy.

    CONCLUSIONS: This report of a novel chemotherapy for androgen-independent malignancy corroborates our understanding of the implications of prolactin in its development and treatment. There are about 165,000 cases/year with 25,000 deaths/year in the U.S.; and 1.0 million cases/year with 260,000 deaths/year worldwide. Those patients with androgen-independent prostate cancer can now employ this cabergoline treatment to prevent or terminate this deadly type of prostate cancer.

    Costello LC, Franklin RB, Yu GW. A Novel Patient Case Report to Show the Successful Termination of Untreatable Androgen-independent Prostate Cancer: Treatment with Cabergoline (Dopamine agonist). Mathews J Case Rep. 2019;4(1):42. A Novel Patient Case Report to Show the Successful Termination of Untreatable Androgen-independent Prostate Cancer: Treatment with Cabergoline (Dopamine agonist).
     
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Kardoust Parizi M, Abufaraj M, Fajkovic H, et al. Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis. Urologic Oncology: Seminars and Original Investigations 2019. Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis - ScienceDirect

    Highlights
    · Testosterone replacement therapy after prostate cancer definitive therapy with curative intent in hypogonadal men does not increase the risk of biochemical recurrence.
    · Hypogonadal men treated with radical prostatectomy experience lower biochemical recurrence rates than those who undergo primary nonsurgical therapies such as external beam radiation therapy, brachytherapy, cryotherapy, or high-intensity focused ultrasound after testosterone replacement therapy.

    Aim: To evaluate the association between testosterone replacement therapy (TRT) in prostate cancer (CaP) patients who underwent definitive local therapy with curative intent with biochemical recurrence (BCR).

    Materials and methods: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on November 2018 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines. The pooled BCR rate in CaP men treated with TRT after definitive local therapy with curative intent was calculated using a random effects model.

    Results: Twenty-one studies were eligible. The overall pooled BCR rate was 0.01 (95%CI 0.00–0.02) suggesting a lack of association between TRT and BCR; there was no heterogeneity among included studies (I2 = 24.34%, P = 0.15). In subgroup analyses, pooled BCR rates were 0.00 (95%CI 0.00–0.02) in patients treated with radical prostatectomy and 0.02 (95%CI 0.00–0.04) in patients treated with external beam radiation therapy, brachytherapy, cryotherapy, or high intensity focused ultrasound; there was no heterogeneity in the subgroup analyses (I2 = 19.88%, P = 0.18).

    Conclusions: In this systematic review and meta-analysis, we did not observe higher rate of BCR after TRT for nonmetastatic CaP patients after definitive local therapy. Based on these data, others and we have outlined a phase I/II trial assessing the safety and benefits of TRT in select men with secondary symptomatic hypogonadism who have no active disease after definitive local CaP therapy with curative intent.
     
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Management Algorithms for Prostate-Specific Antigen Progression in Prostate Cancer: Biochemical Recurrence After Definitive Therapy and Progression to Non-Metastatic Castrate-Resistant Prostate Cancer

    INTRODUCTION: Current prostate cancer (PC) guidelines primarily focus on localized or metastatic PC. A multidisciplinary genitourinary oncology panel determined that additional guidance focusing on monitoring and management of biochemical recurrence (BCR) following radical therapy and non-metastatic castration-resistant prostate cancer (nmCRPC) was warranted.

    METHODS: The most up-to-date national and international guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining optimal monitoring and treatment for patients with non-metastatic PC.

    RESULTS: A total of eight major national and international guidelines/consensus statements published since 2015 and three phase 3 trials were identified. Working group discussions among the multidisciplinary genitourinary oncology panel led to the development of two algorithms: the first addressing management of patients with BCR following radical therapy (post-BCR), and the second addressing management of nmCRPC.

    The post-BCR algorithm suggests consideration of early salvage treatment in select patients, and provides guidance regarding observation vs. intermittent or continuous androgen-deprivation therapy (ADT).

    The nmCRPC algorithm suggests continued ADT and monitoring for all patients, with consideration of treatment with apalutamide or enzalutamide for patients with high-risk disease (prostate-specific antigen [PSA] doubling time of </=10 months).

    CONCLUSIONS: Two treatment algorithms have been developed to guide the management of non-metastatic PC, and should be considered in the context of local guidelines and practice patterns.

    Danielson B, Saad F, So A, et al. Management algorithms for prostate-specific antigen progression in prostate cancer: Biochemical recurrence after definitive therapy and progression to non-metastatic castrate-resistant prostate cancer. Canadian Urological Association journal = Journal de l'Association des urologues du Canada 2019. Management algorithms for prostate-specific antigen progression in prostate cancer: Biochemical recurrence after definitive therapy and progression to non-metastatic castrate-resistant prostate cancer | Canadian Urological Association Journal
     
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    MRI bests systematic biopsies for diagnosing prostate cancer
    https://www.journalofclinicalpathwa...ystematic-biopsies-diagnosing-prostate-cancer

    NEW YORK (Reuters Health) - Magnetic resonance imaging (MRI) is better than systematic biopsies for diagnosing prostate cancer, thereby reducing redundant biopsies, a Cochrane review and meta-analysis revealed. Redirecting

    The findings are practice-changing, coauthor Dr. Ivo Schoots of Erasmus University Medical Center Rotterdam told Reuters Health by email. "Based on the data of the Cochrane Review, the European Association of Urology...decided to change their (prostate cancer) recommendations in March 2019."

    "The joint International PI-RADS steering committee on prostate MRI also strongly supports this strategy," he noted. (http://bit.ly/2YDzQFO ) "The UK NICE guidelines on prostate cancer were also recently changed to an upfront MRI strategy in the diagnostic work-up." (NICE recommends MRI for suspected prostate cancer to reduce biopsies )

    Although US guidelines have not yet changed, Dr. Schoots is convinced this will happen over time.

    "Recommending upfront MRI in all men suspected to have prostate cancer is justified," he added, "based on 1) the potential reduction of biopsies of approximately one-third of tested men whose prostate MRI does not show any suspicious regions; 2) the lower detection rates of insignificant prostate cancer by the MRI pathway in comparison to systematic biopsy; and 3) at least an equal detection of clinically important prostate cancers by the MRI pathway and systematic biopsy."

    "However, MRI is 'waterproof' but not 'watertight', and where there is a high probability of clinically significant prostate cancer, systematic biopsies should remain a very real option even in men with negative MRI scans," he said.

     
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  9. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Prostate Magnetic Resonance Imaging, with or Without Magnetic Resonance Imaging-targeted Biopsy, and Systematic Biopsy for Detecting Prostate Cancer

    Context - Magnetic resonance imaging (MRI), with or without MRI-targeted biopsy (MRI pathway), is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision making.

    Objective - To determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, MRI pathway, and systematic biopsy, as compared with template-guided biopsy (reference standard), in detecting clinically significant prostate cancer, defined as International Society of Urological Pathology grade 2 or higher, in biopsy-naive men or those with a prior-negative biopsy (or mix of both).

    Evidence acquisition - We systematically searched the literature and considered for inclusion any cross-sectional study if it investigated
    (1) one or more index tests verified by the reference standard, and
    (2) paired testing of the MRI pathway with systematic biopsy.

    Quality and certainty of evidence were assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation, respectively.

    Evidence synthesis - Accuracy analyses: Using a baseline cancer prevalence of 30%, MRI pathway (sensitivity 0.72 [95% confidence interval {CI}: 0.60–0.82]; specificity 0.96 [0.94–0.98]; eight studies) may result in 216 (180–246) true positives, 28 (14–42) false positives, 672 (658–686) true negatives, and 84 (54–120) false negatives per 1000 men. Systematic biopsy (sensitivity 0.63 [0.19–0.93]; specificity 1.00 [0.91–1.00]; four studies) may result in 189 (57–279) true positives, 0 (0–63) false positives, 700 (637–700) true negatives, and 111 (21–243) false negatives per 1000 men.

    Agreement analyses: With a direct comparison of the MRI pathway with systematic biopsy concerning significant disease, we found pooled detection ratios of 1.05 (95% CI: 0.95–1.16; 20 studies) in biopsy-naive men and 1.44 (1.19–1.75; 10 studies) in men with a prior-negative biopsy. Concerning insignificant disease, we found detection ratios of 0.63 (95% CI: 0.54–0.74), and 0.62 (95% CI: 0.44–0.88), respectively.

    Conclusions - MRI pathway had the most favourable outcome in significant and insignificant prostate cancer detection compared with systematic biopsy. The certainty in our findings was reduced by study limitations.

    Patient summary - We reviewed recent advances in prostate biopsy by magnetic resonance imaging (MRI) guidance and targeting for prostate cancer detection in comparison with standard diagnosis by systematic biopsies.

    The findings of this Cochrane review suggest that MRI pathway is better than systematic biopsies in making a correct diagnosis of clinically important prostate cancer and reducing redundant biopsies and the detection of unimportant cancers substantially.

    However, MRI pathway still misses some men with important prostate cancer. Therefore, further research in this area is important.

    Drost F-JH, Osses D, Nieboer D, et al. Prostate Magnetic Resonance Imaging, with or Without Magnetic Resonance Imaging-targeted Biopsy, and Systematic Biopsy for Detecting Prostate Cancer: A Cochrane Systematic Review and Meta-analysis. European Urology. Redirecting
     
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Quality of YouTube Patient Information on Prostate Cancer Screening

    Social media is used by patients for health care information. We analyzed the quality of YouTube videos on prostate cancer screening. Most videos (71.1%) mentioned the potential harms of prostate cancer screening.

    There was no significant difference in risk-related information between videos published before and after the publication of US Preventive Services Task Force 2012 guidelines for prostate cancer screening.

    In conclusion, the quality of information of YouTube videos on prostate cancer screening is low and the content is potentially misleading.

    Basnet B, Bhattarai S, Khanal A, Upadhyay M, Baruwal A. Quality of YouTube patient information on prostate cancer screening. Proceedings (Baylor University Medical Center) 2019;32:361-3. Quality of YouTube patient information on prostate cancer screening
     
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  11. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] testosterone Therapy: A Friend or A Foe for The Aging Men with Benign Prostatic Hyperplasia?

    One of the major concerns for the prescription of medications containing testosterone (T) in the aging men with T deficiency (TD) is prostate disorders (such as benign prostatic hyperplasia, BPH) and their related symptoms (lower urinary tract symptoms, LUTS).

    This is because prostate is an androgen-responsive gland; however, the androgen dependence of prostate growth, well demonstrated in earlier phases of life, has no clear evidence in late adulthood and senescence.

    In fact, after the age of 40 years, BPH becomes increasingly more prevalent. On the other hand, in men older than 40 year, a progressive decline in T is observed.

    These epidemiological data are a starting point for questioning a putative detrimental role of T on the prostate health in the ageing man.

    Rastrelli G, Vignozzi L, Maggi M. Testosterone therapy: a friend or a foe for the aging men with benign prostatic hyperplasia? Asian journal of andrology 2019. Testosterone therapy: a friend or a foe for the aging men with benign prostatic hyperplasia? Rastrelli G, Vignozzi L, Maggi M, - Asian J Androl
     
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    A 66-Year-Old Man with PSA-Detected Prostate Cancer and Regrets

    LOOPING EFFECTS - A substantial portion of our knowledge about disease, treatment, and prognosis is contingent, meaning that many perceived medical truths may eventually be determined to be false. “Looping effects” describes the ways in which feedback patterns among diagnosis, therapeutic interventions, and health behaviors influence the natural history and prognosis of diseases. Knowledge produced by our investigations and interventions changes the way we diagnose and treat people, which in turn transforms the epidemiology and clinical profile of disease itself.

    A 66-year-old man with PSA-detected prostate cancer undergoes prostatectomy that leaves him impotent — a decision he regrets when new evidence becomes available. How can the largely social processes by which we identify diseases transform diseases themselves?

    In 2006, Mr. B., a 66-year-old economics professor, learned from his general internist that his prostate-specific antigen (PSA) level was 4.5 ng per milliliter, up from 3.0 ng per milliliter the previous year. His urologist, who found only mild prostatic enlargement on examination, confirmed an elevated PSA level and recommended a biopsy. Mr. B. consented. Two of 12 biopsy specimens showed cancer, with a Gleason score of 7.

    After presenting the options of radical prostatectomy, radiation, and active surveillance, the urologist indicated a strong preference for surgery, while acknowledging that it could lead to impotence and incontinence. Before consenting, Mr. B. met with a medical oncologist to discuss the option of active surveillance.

    Knowing that Mr. B. had a background in quantitative social science, the oncologist sent two relevant research articles to Mr. B. by email before his appointment. The studies, which had begun before PSA screening became routine, showed a clear survival benefit for surgery in men with localized cancer. These studies, plus the oncologist’s review of expert guidelines, led him to recommend surgery or radiation.

    Influenced by this evidence, by a colleague’s recent painful death from prostate cancer, and by his wife’s strong opinion that he should “do everything” to avoid death from prostate cancer, Mr. B. underwent robot-assisted radical prostatectomy.

    Afterward, he had urinary incontinence, which slowly resolved, and impotence that has continued despite several rehabilitation programs and pharmaceutical interventions. His PSA has remained at the zero-to-negligible level.

    Mr. B. initially saw his impotence as the unfortunate effect of a rational decision that may have saved his life. But in 2009, early results in two large, randomized, controlled trials of PSA screening showed equivocal or no benefit. The rationality of Mr. B.’s decision to undergo surgery now seemed to be undermined by earlier decisions that he’d made casually: consenting to the initial PSA test and to the biopsy.

    His doubts increased when, a few years later, a trial that began after PSA screening became routine revealed no overall survival benefit of surgery over active surveillance for localized disease. Mr. B. struggled to understand how the data he’d reviewed just a few years earlier had made him confident about surgical intervention.

    Aronowitz R, Greene JA. Contingent Knowledge and Looping Effects — A 66-Year-Old Man with PSA-Detected Prostate Cancer and Regrets. New England Journal of Medicine 2019;381:1093-6. https://doi.org/10.1056/NEJMp1811521