Prostate ...

[Michael Scally MD]

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

 

[Michael Scally MD]

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

 

[Michael Scally MD]

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.

 

[Michael Scally MD]

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

 

[Michael Scally MD]

[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).

 

[Michael Scally MD]

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.

 

[Michael Scally MD]

[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

 

[Michael Scally MD]

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.

…

 

[Michael Scally MD]

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

 

[Michael Scally MD]

[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

 

[Michael Scally MD]

[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

 

[Michael Scally MD]

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

 

[Michael Scally MD]

And imagine if PSA counseling included this truth, "This screening test has never shown it improves survival (aka all cause mortality). Not in individual studies nor pooled analysis"

 

[Michael Scally MD]

[OA] Risk of Prostate Cancer for Men Fathering Through Assisted Reproduction

Objective To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally.

Design National register based cohort study.

Setting Sweden from January 1994 to December 2014.

Participants 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception.

Main outcome measures Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy).

Results Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively.

Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07).

Conclusions Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.

Al-Jebari Y, Elenkov A, Wirestrand E, Schütz I, Giwercman A, Lundberg Giwercman Y. Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study. BMJ (Clinical research ed) 2019;366:l5214. Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study

 

[Michael Scally MD]

[OA] Risk of Prostate Cancer for Men Fathering Through Assisted Reproduction

Objective To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally.

Design National register based cohort study.

Setting Sweden from January 1994 to December 2014.

Participants 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception.

Main outcome measures Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy).

Results Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively.

Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07).

Conclusions Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.

Al-Jebari Y, Elenkov A, Wirestrand E, Schütz I, Giwercman A, Lundberg Giwercman Y. Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study. BMJ (Clinical research ed) 2019;366:l5214. Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study

[OA] Assisted Reproduction and Risk of Prostate Cancer for Men
Assisted reproduction and risk of prostate cancer for men - The BMJ

For many people having children is an important aspect of life. Yet as many as 15-20% of all couples struggle to conceive naturally. One of the solutions available for couples is to go through assisted reproduction. It is understandable that healthcare providers and patients only focus on what they consider to be the main aim—to have a baby. However, the struggle to conceive has been shown to be associated with a multitude of future morbidities among men, ranging from metabolic syndrome to autoimmune disease.

In general, men do not undergo any systematic screening or health check-ups, as is common for women from a young age, who have doctor’s appointments for contraceptives or mammographies. These check-ups may well provide an opportunity for women to discuss their health more generally and also help normalise healthcare visits.

Many men, on the other hand, tend to avoid healthcare visits altogether, until medical help cannot be ducked any longer. Applying a more long term view, and seeing infertility as an early symptom of general disease, opens up the possibility of offering preventive health measures to a significant proportion of the male population, specifically to those with higher risks for a wide range of disease.

Our new research paper supports this long term view. The study shows that men undergoing assisted reproduction have a large risk increase for prostate cancer. The paper showed that men undergoing intra cytoplasmic sperm injection, the treatment usually reserved for cases of severe male infertility, had the largest risk increase, especially for the early onset variant of prostate cancer. This is particularly important since early onset prostate cancer has long been known to be more aggressive, with corresponding higher mortality rates, and precautionary measures for this disease are rarely adopted before the age of 50 years. That said, the results presented should not cause concern among men undergoing assisted reproduction.

…

 

[Michael Scally MD]

[OA] [Editorial] Male Infertility Linked to Risk of Prostate Cancer

The mechanism isn’t clear but abnormalities on the Y chromosome are in the frame.

Poor sperm function (male infertility) causes nearly half of all infertility. The observation that poor sperm function is commonly associated with developmental genitourinary defects such as cryptorchidism suggests that male infertility could be a risk marker for later disease. Unfortunately, we know little about the natural history of male infertility beyond reproductive life, owing to historical social stigma experienced by affected men.

Studies shedding light on the future health of infertile men should be welcomed, and in the linked paper (doi:10.1136/bmj.l5214) Al-Jebari and colleagues report analyses of registry data from the whole population of Sweden over 20 years. Their results provide the strongest evidence to date that risk of prostate cancer may be increased in infertile men. Importantly though, a causal relation cannot be assumed.

…

Sharma A, Jayasena CN. Male infertility linked to risk of prostate cancer. BMJ (Clinical research ed) 2019;366:l5525. Male infertility linked to risk of prostate cancer

 

[Uglyrichie]

Quick ? I don't know if you already touched on it. My doc says they are no longer doing prostate exams the reasoning behind it was exams did not help with prevention but only detected prostate cancer that had all ready started. I hope this makes sense have they discovered other ways to detect a precancerous prostate?
Thank you for your time

 

[Michael Scally MD]

Prostate Cancer in Young Men

BACKGROUND: Recent observations suggest that prostate cancer is an increasing disease among older adolescents and young adults.

METHODS: Incidence, mortality, and survival data were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results program and the Institute for Health Metrics and Evaluation Global Burden of Disease database.

RESULTS: Worldwide, the incidence of prostate cancer has increased in all groups between ages 15 and 40 years and increased globally at a steady rate averaging 2% per year since 1990 (P < .01).

In the United States, this age group was >6 times more likely than older men to have distant disease at diagnosis. Stage for stage, their survival rate improved less than in older men. Whereas the overall 5-year relative survival rate in the United States for men diagnosed between ages 40 and 80 years was between 95% and 100%, it was 30% in those aged 15 to 24 years, 50% in those aged 20 to 29 years, and 80% in those aged 25 to 34 years.

CONCLUSIONS: Prostate cancer in older adolescent and young adult men has increased in most countries. There is some evidence that this may be caused in part by underdiagnosis, prostate-specific antigen screening, and overdiagnosis.

It also may be caused by trends in obesity, physical inactivity, HPV infection, substance exposure, environmental carcinogens, and/or referral patterns. How the biology of these cancers differs from that in older men and how the etiologies vary from country to country remain to be determined.

Bleyer A, Spreafico F, Barr R. Prostate cancer in young men: An emerging young adult and older adolescent challenge. Cancer 2019. https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32498

 

[Michael Scally MD]

Prostate Cancer in Young Men

BACKGROUND: Recent observations suggest that prostate cancer is an increasing disease among older adolescents and young adults.

METHODS: Incidence, mortality, and survival data were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results program and the Institute for Health Metrics and Evaluation Global Burden of Disease database.

RESULTS: Worldwide, the incidence of prostate cancer has increased in all groups between ages 15 and 40 years and increased globally at a steady rate averaging 2% per year since 1990 (P < .01).

In the United States, this age group was >6 times more likely than older men to have distant disease at diagnosis. Stage for stage, their survival rate improved less than in older men. Whereas the overall 5-year relative survival rate in the United States for men diagnosed between ages 40 and 80 years was between 95% and 100%, it was 30% in those aged 15 to 24 years, 50% in those aged 20 to 29 years, and 80% in those aged 25 to 34 years.

CONCLUSIONS: Prostate cancer in older adolescent and young adult men has increased in most countries. There is some evidence that this may be caused in part by underdiagnosis, prostate-specific antigen screening, and overdiagnosis.

It also may be caused by trends in obesity, physical inactivity, HPV infection, substance exposure, environmental carcinogens, and/or referral patterns. How the biology of these cancers differs from that in older men and how the etiologies vary from country to country remain to be determined.

Bleyer A, Spreafico F, Barr R. Prostate cancer in young men: An emerging young adult and older adolescent challenge. Cancer 2019. https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32498

Sartor O. Why is prostate cancer incidence rising in young men? Cancer 2019. https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32497

Globally, prostate cancer in young men is increasing in incidence. The reasons for this increase are unclear but may include ascertainment bias caused by increases in prostate‐specific antigen testing.

 

[Uglyrichie]

Thank you sir