Prostate ...

[Michael Scally MD]

Lepor H, Shore ND. LHRH Agonists for the Treatment of Prostate Cancer: 2012. Rev Urol 2012;14(1-2):1-12. LHRH Agonists for the Treatment of Prostate Cancer: 2012

The most recent guidelines on prostate cancer screening from the American Urological Association (2009), the National Comprehensive Cancer Network (2011), and the European Association of Urology (2011), as well as treatment and advances in disease monitoring, have increased the androgen deprivation therapy (ADT) population and the duration of ADT usage as the first-line treatment for metastatic prostate cancer. According to the European Association of Urology, gonadotropin-releasing hormone (GnRH) agonists have become the leading therapeutic option for ADT because they avoid the physical and psychological discomforts associated with orchiectomy. However, GnRH agonists display several shortcomings, including testosterone (T) surge ("clinical flare") and microsurges. T surge delays the intended serologic endpoint of T suppression and may exacerbate clinical symptoms. Furthermore, ADT manifests an adverse-event spectrum that can impact quality of life with its attendant well-documented morbidities. Strategies to improve ADT tolerability include a holistic management approach, improved diet and exercise, and more specific monitoring to detect and prevent T depletion toxicities. Intermittent ADT, which allows hormonal recovery between treatment periods, has become increasingly utilized as a methodology for improving quality of life while not diminishing chronic ADT efficacy, and may also provide healthcare cost savings. This review assesses the present and potential future role of GnRH agonists in prostate cancer and explores strategies to minimize the adverse-event profile for patients receiving ADT.

 

[BBC3]

https://thinksteroids.com/community/posts/849745

About the above thread: I did not want to place the "silly context" (at least in title) of the above listed thread here, as it was created as a feeler guage to attempt to determine how may men can distinguish the ability to control urine flow, how precisely, and with regard ALSO to how many men have difficulty CUTTING OFF the urine flow DENOTED as the ever notorious "I cant stop once I start phenomenon", and how it may related.?

So my question with regard to formal Prostate cancer research is; are there studies involving mens' urinary habits & history, how does urine actually interact & involve with the prostate, and how all this may related to prostate health longevity.?

 

[Michael Scally MD]

Stricker PD, Frydenberg M, Kneebone A, Chopra S. Informed prostate cancer risk-adjusted testing: a new paradigm. BJU Int 2012;110 Suppl 4:30-4. Informed prostate cancer risk-adjusted testing: a new paradigm - Stricker - 2012 - BJU International - Wiley Online Library

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?:

There is now clear evidence that prostate-specific antigen testing will reduce death from prostate cancer and this data can be used to define those subgroups of men that most stand to benefit from prostate cancer screening. This will help minimise over-detection and improve information provided, so men can provide informed consent.

We feel that risk-adjusted screening guidelines, such as the one proposed in the present article, should become the new standard for prostate cancer testing, which will hopefully resolve some of the confusion held by patients and clinicians alike.

? Currently there is significant confusion and polarisation about prostate cancer screening for both patients and physicians alike.

? We propose a risk-adjusted testing programme, which would lead to fewer patients who need to be tested and treated to save a life and also eliminate inappropriate prostate-specific antigen testing in the elderly and patients with severe co-morbidities where there is no clear benefit.

 

[Michael Scally MD]

Saturation Of Prostate Growth With Regard To Testosterone

Traditional androgen dependent view of prostate assumed growth would increase as serum T concentrations increased (curves a and b). Current evidence suggests that prostate growth and its surrogate, PSA, are sensitive to changes in serum T at low extreme of T concentrations (androgen sensitive) and reach growth plateau as serum T increases. Once this growth plateau is reached, presumably due to maximal binding of androgen to AR, system is considered saturated and no further prostate growth occurs even with large increases in T (androgen indifferent) (curve c).


Morgentaler A. Testosterone Therapy in Men With Prostate Cancer: Scientific and Ethical Considerations. The Journal of Urology 2013;189(1, Supplement):S26-S33. ScienceDirect.com - The Journal of Urology - Testosterone Therapy in Men With Prostate Cancer: Scientific and Ethical Considerations

Purpose Pertinent literature regarding the potential use of testosterone therapy in men with prostate cancer is reviewed and synthesized.

Materials and Methods A literature search was performed of English language publications on testosterone administration in men with a known history of prostate cancer and investigation of the effects of androgen concentrations on prostate parameters, especially prostate specific antigen.

Results The prohibition against the use of testosterone therapy in men with a history of prostate cancer is based on a model that assumes the androgen sensitivity of prostate cancer extends throughout the range of testosterone concentrations. Although it is clear that prostate cancer is exquisitely sensitive to changes in serum testosterone at low concentrations, there is considerable evidence that prostate cancer growth becomes androgen indifferent at higher concentrations. The most likely mechanism for this loss of androgen sensitivity at higher testosterone concentrations is the finite capacity of the androgen receptor to bind androgen. This saturation model explains why serum testosterone appears unrelated to prostate cancer risk in the general population and why testosterone administration in men with metastatic prostate cancer causes rapid progression in castrated but not hormonally intact men. Worrisome features of prostate cancer such as high Gleason score, extracapsular disease and biochemical recurrence after surgery have been reported in association with low but not high testosterone. In 6 uncontrolled studies results of testosterone therapy have been reported after radical prostatectomy, external beam radiation therapy or brachytherapy. In a total of 111 men 2 (1.8%) biochemical recurrences were observed. Anecdotal evidence suggests that testosterone therapy does not necessarily cause increased prostate specific antigen even in men with untreated prostate cancer.

Conclusions Although no controlled studies have been performed to date to document the safety of testosterone therapy in men with prostate cancer, the limited available evidence suggests that such treatment may not pose an undue risk of prostate cancer recurrence or progression.

 

[Millard]

"When you have got [cancer] you monitor it and you have to be careful it doesn't spread. But if it is contained in the prostate it’s no big deal," McKellen, who is 73, told the Daily Mirror. "Many, many men die from it but it's one of the cancers that is totally treatable so I have 'waitful watching.' I am examined regularly and it's just contained, it's not spreading. I’ve not had any treatment."

Watchful Waiting: Ian McKellen's 'Active Surveillance' Approach To Prostate Cancer, Explained

 

[BBC3]

I wonder did he cut out the anal sex?!? LOL

Seriously, the man is a great actor and a legend as far as I am concerned. Perferable in the XMen Series (Magneto) to me.

Points:
- Its my notion that while hormone imbalance contributes and may even be a primary cause in many forms of PC, I would suspect that once the cancer is in place, additional hormones of any type are not a good thing as now only gas on a fire. HE IS - O. L. D. and therefore steeply declining in hormones at 73.
- I would hazzard to gamble that "Watchful Waiting" (no doubt soon to be the title of a movie) is not the protocol for anyone with a discernable mass as young as 50 or so. Its such a lovely political term though.
- Sadly, there are $Political Rammification$ surely. As to WHO gets treated and who does not OR HOW. MORE SPECIFICALLY what KIND of treatment they get. I would how many Urologists have remained silent with a patient when they feel something not quite rite on digital exam?!? What the motives are based on the influences on them? How many prostates may have a "strange feel" even though NO lumps, shape changes, "hardnesses", whatever is found?! But you have to KNOW that a urologist lives with his finger in mens asses for a LIVING - day in and out. He knows how EVERY DAMN ONE of them should feel at certain ages and conditions, and he knows whos out of the curve regardless of current medical POLITICS. No, I dont believe there is any great conspiracy to save BC/BS some $$ at this time in the US, but then again, what DO YOU tell a man with no IN$URANCE?!?!
- "BUT WHATS THE POINT" - He might tell himself... Cant go cuttin on this 40 year old guy on a hunch. "Really dont want to risk spreading it by pokin round with my floundering gig either". "Hell, maybe the guy even shit a turn out sideways last night" - LOL. The patient qualifies for a verbal desription of his findings as "NORMAL" at best. So what about the guy who might actually make a change if he knew?!?! ANd I am not saying there aren't "alarm docs out there who just spread caution at every turn either. The point is that the treatment is so harsh considering the principle prostate, and all that it connotates, that nothing can be done in many light instances.

- Then again, here let me give you this FInasteride - I wont dare to go there... Today...

McKellan being 73 is really at an interesting crossroad and a PRIME candidate for a PUBLIC CASE STUDY of "watecfull waiting". So I find that interesting in just that aspect alone. He is at the age where hormones are just about out of play in nature, yet probably young enought that he aint just sitting down to play Yatzee... He is a PRIME EXAMPLE of probably the toughest decision process he will ever go through and due to the exact conditions relative to him and now. I knew a man that was diagnosed about that age. He made it five more years. But the question is where was his status when found, and WHAT type PC was it. So it should be intersting to watch McKellen if he has had regular screenings and caught it right as it materialized. And to see how "watchful waiting" pans out for him. I suspect the person I referred to was far beyond an early stage detection in that they may have slacked on THE FINGER TRIP. So not putting the Whammy on McKellan at all and wish him only the best.!!

You can bet in the past, MANY men were not getting prostate exams. I am sure business is up with all the press available today. The REAL TEST of Watchfull Waiting will be deteriming WHO is diagnosed as early as the cancer could possibly be found, and who waited too long to be diagnosed. IMPORTANTLY, the diagnosing docs ACTIVE PROTOCAL at Publicizing the a problem to the patient as now "officially" percieved as enough of a threat to merit a Poke (biopsy) and confirmation, which is what I was building up to.. When is the problem a problem, and/so when does watchfull waiting actually ever even start. As men, we are waiting and watching our WHOLE LIVES past the age of 35 or 40. Where did this slip by?

"When you have got [cancer] you monitor it and you have to be careful it doesn't spread. But if it is contained in the prostate it’s no big deal," McKellen, who is 73, told the Daily Mirror. "Many, many men die from it but it's one of the cancers that is totally treatable so I have 'waitful watching.' I am examined regularly and it's just contained, it's not spreading. I’ve not had any treatment."

Watchful Waiting: Ian McKellen's 'Active Surveillance' Approach To Prostate Cancer, Explained

 

[Michael Scally MD]

Targeted Prostate Biopsy using MR-Ultrasound Fusion
[ame=http://www.youtube.com/watch?v=IcLwL2dcK5o]Targeted Prostate Biopsy using MR-Ultrasound Fusion - YouTube[/ame]


Sonn GA, Natarajan S, Margolis DJA, et al. Targeted Biopsy in the Detection of Prostate Cancer Using an Office Based Magnetic Resonance Ultrasound Fusion Device. The Journal of Urology 2012;189(1):86-92. Elsevier

Purpose - Targeted biopsy of lesions identified on magnetic resonance imaging may enhance the detection of clinically relevant prostate cancers. We evaluated prostate cancer detection rates in 171 consecutive men using magnetic resonance ultrasound fusion prostate biopsy.

Materials and Methods - Subjects underwent targeted biopsy for active surveillance (106) or persistently increased prostate specific antigen but negative prior conventional biopsy (65). Before biopsy, each man underwent multiparametric magnetic resonance imaging at 3.0 Tesla. Lesions on magnetic resonance imaging were outlined in 3 dimensions and assigned increasing cancer suspicion levels (image grade 1 to 5) by a uroradiologist. A biopsy tracking system was used to fuse the stored magnetic resonance imaging with real-time ultrasound, generating a 3-dimensional prostate model on the fly. Working from the 3-dimensional model, transrectal biopsy of target lesions and 12 systematic biopsies were performed with the patient under local anesthesia in the clinic.

Results - A total of 171 subjects (median age 65 years) underwent targeted biopsy. At biopsy, median prostate specific antigen was 4.9 ng/ml and prostate volume was 48 cc. A targeted biopsy was 3 times more likely to identify cancer than a systematic biopsy (21% vs 7%). Prostate cancer was found in 53% of men, 38% of whom had Gleason grade 7 or greater cancer. Of the men with Gleason 7 or greater cancer 38% had disease detected only on targeted biopsies. Targeted biopsy findings correlated with level of suspicion on magnetic resonance imaging. Of 16 men 15 (94%) with an image grade 5 target (highest suspicion) had prostate cancer, including 7 with Gleason 7 or greater cancer.

Conclusions - Prostate lesions identified on magnetic resonance imaging can be accurately targeted using magnetic resonance ultrasound fusion biopsy by a urologist in clinic. Biopsy findings correlate with level of suspicion on magnetic resonance imaging.

 

[Michael Scally MD]

Shi Y, Han JJ, Tennakoon JB, et al. Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy. Molecular Endocrinology. Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy

Androgens regulate both the physiological development of the prostate and the pathology of prostatic diseases. However, the mechanisms by which androgens exert their regulatory activities on these processes are poorly understood. In this study, we have determined that androgens regulate overall cell metabolism and cell growth, in part, by increasing autophagy in prostate cancer cells. Importantly, inhibition of autophagy using either pharmacological or molecular inhibitors significantly abrogated androgen-induced prostate cancer cell growth. Mechanistically, androgen-mediated autophagy appears to promote cell growth by augmenting intracellular lipid accumulation, an effect previously demonstrated to be necessary for prostate cancer cell growth. Further, autophagy and subsequent cell growth is potentiated, in part, by androgen-mediated increases in reactive oxygen species. These findings demonstrate a role for increased fat metabolism and autophagy in prostatic neoplasias and highlight the potential of targeting underexplored metabolic pathways for the development of novel therapeutics.

 

[Michael Scally MD]

Greene KL, Albertsen PC, Babaian RJ, et al. Prostate specific antigen best practice statement: 2009 update. J Urol 2013;189(1 Suppl):S2-S11. ScienceDirect.com - The Journal of Urology - Prostate Specific Antigen Best Practice Statement: 2009 Update

PURPOSE: We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection.

MATERIALS AND METHODS: The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases.

RESULTS: There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities.

CONCLUSIONS: Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

 

[Michael Scally MD]

Sonn GA, Sadetsky N, Presti JC, Litwin MS. Differing perceptions of quality of life in patients with prostate cancer and their doctors. J Urol 2013;189(1 Suppl):S59-65. Elsevier

PURPOSE: As the number of prostate cancer survivors increases, urologists must recognize their quality of life impairment. In the past physician ratings of patient symptoms did not correlate with patient self-assessments. We determined if urologists have improved their reporting of patient health related quality of life. We also investigated if urologists assessed health related quality of life more accurately in the short or long term.

MATERIALS AND METHODS: We identified 1,366 men from CaPSURE, a national, prospective cohort, who had undergone prostatectomy, brachytherapy or external beam radiation therapy. At each visit urologists assessed fatigue, pain, and sexual, urinary and bowel dysfunction. Participants independently completed the SF-36 and the UCLA-PCI. We contrasted the frequency of impairment reported by physicians and participants in select health related quality of life domains in the short (less than 1 year) and long (greater than 2 years) term. We also compared physician-patient concordance between the periods 1995 to 2000 and 2001 to 2007.

RESULTS: In short-term and long-term followup, and for the 1995 to 2000 and 2001 to 2007 cohorts, physician and participant assessments differed in all analyzed domains. Urologists noted impairment in urinary and sexual function more often than fatigue or pain. Disagreement between physician and participant ratings did not vary dramatically from short-term to long-term followup, or from the earlier to the later cohort.

CONCLUSIONS: In men treated for localized prostate cancer physician ratings of symptoms do not correlate well with patient self-assessments of health related quality of life. Physician reporting did not improve over time. It is increasingly important to recognize and address impairments in quality of life from prostate cancer and its treatment.

 

[Michael Scally MD]

Arai S, Shibata Y, Nakamura Y, et al. Development of prostate cancer in a patient with primary hypogonadism: intratumoural steroidogenesis in prostate cancer tissues. Andrology 2013;1(1):169-74. Development of prostate cancer in a patient with primary hypogonadism: intratumoural steroidogenesis in prostate cancer tissues - Arai - 2012 - Andrology - Wiley Online Library

Intratumoural steroidogenesis may play a significant role in the progression of prostate cancer (PC) in the context of long-term ablation of circulating testosterone (T). To clarify the mechanism accounting for the progression of PC in a 74-year-old man who had undergone bilateral orchiectomy when he was 5 years old, we performed immunohistochemical studies of androgen receptor (AR) and steroidogenic enzymes in the prostate. We also measured steroid hormone levels in the serum and prostate, as well as mRNA levels of genes mediating androgen metabolism in the prostate.

Positive nuclear staining of AR was detected in malignant epithelial cells. The levels of androstenedione (Adione), T, and 5-alpha dihydrotestosterone (DHT) in the serum of the patient were similar to those in PC patients receiving neoadjuvant androgen deprivation therapy (ADT), but were higher in the patient's prostate than in PC patients not receiving ADT. The gene expression of CYP17A1 and HSD3B1 was not detected, whereas that of STS, HSD3B2, AKR1C3, SRD5A1, and SRD5A2 was detected. Moreover, cytoplasmic staining of HSD3B2, AKR1C3, SRD5A1, and SRD5A2 was detected in malignant epithelial cells.

Hence, in the present case (a man with primary hypogonadism), steroidogenesis in PC tissues from adrenal androgens, especially dehydroepiandrosterone sulphate, was the mechanism accounting for progression of PC. This mechanism might help elucidate the development of castration-resistant PC.

 

[Michael Scally MD]

Etzioni R, Gulati R, Cooperberg MR, Penson DM, Weiss NS, Thompson IM. Limitations of Basing Screening Policies on Screening Trials: The US Preventive Services Task Force and Prostate Cancer Screening. Med Care. Limitations of Basing Screening Policies on Screening Trials... : Medical Care

BACKGROUND: The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.

OBJECTIVE: To examine limitations of basing screening policy on evidence from screening trials.

METHODS: We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results.

RESULTS: Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately, 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial.

CONCLUSIONS: Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

 

[Michael Scally MD]

This issue was devoted to PrCa - Table of Contents — September 2012, 2012 (45)

Sandhu GS, Andriole GL. Overdiagnosis of prostate cancer. J Natl Cancer Inst Monogr. 2012(45):146-51. Overdiagnosis of Prostate Cancer

This chapter addresses issues relevant to prostate cancer overdiagnosis. Factors promoting the overdiagnosis of prostate cancer are reviewed.

First is the existence of a relatively large, silent reservoir of this disease, as can be seen by evaluating autopsy studies and histologic step-sectioning results of prostates removed for other causes.

The second main factor responsible for prostate cancer overdiagnosis is fairly widespread prostate-specific antigen and digital rectal examination-based screening, which has been fairly widely practiced in the United States for the past 20 years among heterogeneous groups of men. This has resulted in the identification of many men from this reservoir who otherwise may never have been diagnosed with symptomatic prostate cancer and is substantially responsible for the current annual incidence to mortality ratio for prostate cancer of approximately 6 to 1.

Finally, the relatively indolent natural history and limited cancer-specific mortality as reported in a variety of contemporary randomized screening and treatment trials is reviewed.

We attempt to quantitate the proportion of newly diagnosed prostate cancers that are overdiagnosed using various trial results and models. We explore the impact of prostate cancer overdiagnosis in terms of patient anxiety and the potential for overtreatment, with its attendant morbidity. We explore strategies to minimize overdiagnosis by targeting screening and biopsy only to men at high risk for aggressive prostate cancer and by considering the use of agents such as 5-alpha reductase inhibitors.

Future prospects to prevent overtreatment, including better biopsy and molecular characterization of newly diagnosed cancer and the role of active surveillance, are discussed.

 

[Michael Scally MD]

Ahmed HU. Prostate cancer: Time for active surveillance of intermediate-risk disease? Nat Rev Urol 2013;10(1):6-8. http://www.nature.com/nrurol/journal/v10/n1/full/nrurol.2012.213.html

Active surveillance has become increasingly popular as a management option for localized prostate cancer. Although widely viewed as a means to enable men with low-risk prostate cancer to avoid or defer the effects of whole-gland radical therapy, two new studies demonstrate that it might be a safe approach in intermediate-risk disease.

 

[Michael Scally MD]

Parekh A, Chen M-H, Hoffman KE, et al. Reduced Penile Size and Treatment Regret in Men With Recurrent Prostate Cancer After Surgery, Radiotherapy Plus Androgen Deprivation, or Radiotherapy Alone. Urology;81(1):130-5. Elsevier

Objective - To report the relative incidence of the perceived reduction in penile size across prostate cancer treatment modalities and to describe its effect on quality of life and treatment regret.

Materials and Methods - The incidence of patient complaints about reduced penile size was calculated for 948 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical failure (per registry definition) and were assessed a median of 5.53 years after prostatectomy or radiotherapy (RT) consisting of either external beam RT or brachytherapy, with or without androgen deprivation therapy (ADT). Multivariate logistic regression analysis was used to determine the factors associated with treatment regret and interference with emotional relationships.

Results - Of 948 men, 25 (2.63%) complained of a reduced penile size. The incidence of reduced penile size stratified by treatment was 3.73% for surgery (19 of 510), 2.67% for RT plus ADT (6 of 225), and 0% for RT without ADT (0 of 213). The surgery (P = .004) and RT plus ADT (P = .016) groups had significantly more shortened penis complaints than the RT alone group. The rate of a shortened penis after surgery and after RT plus ADT was similar (P = .47). On multivariate analysis adjusting for age, treatment type, and baseline comorbidity, a perceived reduction in penile size was associated with interference with close emotional relationships (odds ratio 2.36, 95% confidence interval 1.02-8.26; P = .04) and increased treatment regret (odds ratio 3.37, 95% confidence interval 1.37-8.26; P = .0079).

Conclusion - Complaints about a reduced penile size were more common with RT plus ADT or surgery than RT alone and were associated with greater interference with close emotional relationships and increased treatment regret. Physicians should discuss the possibility of this rarely mentioned side effect with their patients to help them make more informed treatment choices.

 

[Michael Scally MD]

Gilgunn S, Conroy PJ, Saldova R, Rudd PM, O'Kennedy RJ. Aberrant PSA glycosylation - a sweet predictor of prostate cancer. Nat Rev Urol;advance online publication. http://www.nature.com/nrurol/journal/vaop/ncurrent/full/nrurol.2012.258.html

Prostate cancer—the most commonly diagnosed cancer in men worldwide—can have a substantial effect on quality of life, regardless of the route the cancer takes. The serum PSA assay is the current gold standard option for diagnosing prostate cancer. However, a growing body of evidence suggests that PSA screening for prostate cancer results in extensive overdiagnosis and overtreatment. It is increasingly evident that the potential harm from overdiagnosis (in terms of unnecessary biopsies) must be weighed against the benefit derived from the early detection and treatment of potentially fatal prostate cancers. Rapid screening methods have been used to analyse glycosylation patterns on glycoproteins in large cohorts of patients, enabling the identification of a new generation of disease biomarkers. Changes to the expression status of certain glycan structures are now widely thought to be common features of tumour progression. In light of this development, much research has focused on the potential role of altered PSA glycosylation patterns in discriminating between significant and insignificant prostate cancers, with the aim of developing a more reliable diagnostic tool than the current serum PSA test.

 

[BBC3]

So perhaps this is a test to help distinguish, if not even determine, the PRE-SENSE of the dreaded "centralized CNS INVOLVED type of prostate cancer". I am only REGALING over what I THINK I read as to a more rare type of PC in which is more central and involved with the nerve bundles central, and I think I recall much more uncurable. AND I DONT REALLY MEAN ALL THAT RARE. But I suspect its a form of PC that pretty much spreads quicker OR has a higher likely hood of coming back systemicly after complete removal of the prostate...? Clearly, if recalling correctly, if would be a particularly NASTY and INCIDEOUS way to get it...

Gilgunn S, Conroy PJ, Saldova R, Rudd PM, O'Kennedy RJ. Aberrant PSA glycosylation - a sweet predictor of prostate cancer. Nat Rev Urol;advance online publication. http://www.nature.com/nrurol/journal/vaop/ncurrent/full/nrurol.2012.258.html

Prostate cancer—the most commonly diagnosed cancer in men worldwide—can have a substantial effect on quality of life, regardless of the route the cancer takes. The serum PSA assay is the current gold standard option for diagnosing prostate cancer. However, a growing body of evidence suggests that PSA screening for prostate cancer results in extensive overdiagnosis and overtreatment. It is increasingly evident that the potential harm from overdiagnosis (in terms of unnecessary biopsies) must be weighed against the benefit derived from the early detection and treatment of potentially fatal prostate cancers. Rapid screening methods have been used to analyse glycosylation patterns on glycoproteins in large cohorts of patients, enabling the identification of a new generation of disease biomarkers. Changes to the expression status of certain glycan structures are now widely thought to be common features of tumour progression. In light of this development, much research has focused on the potential role of altered PSA glycosylation patterns in discriminating between significant and insignificant prostate cancers, with the aim of developing a more reliable diagnostic tool than the current serum PSA test.

 

[Michael Scally MD]

Stott-Miller M, Neuhouser ML, Stanford JL. Consumption of deep-fried foods and risk of prostate cancer. The Prostate. Consumption of deep-fried foods and risk of prostate cancer - Stott-Miller - 2013 - The Prostate - Wiley Online Library

BACKGROUND Evidence suggests that high-heat cooking methods may increase the risk of prostate cancer (PCa). The addition of oil/fat, as in deep-frying, may be of particular concern, and has not specifically been investigated in relation to PCa. Potential mechanisms include the formation of potentially carcinogenic agents such as aldehydes, acrolein, heterocyclic amines, polycyclic aromatic hydrocarbons, and acrylamide.

METHODS We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between tertiles of intake of deep-fried foods from a food frequency questionnaire (French fries, fried chicken, fried fish, doughnuts and snack chips) and PCa risk, adjusted for potential confounders, among 1,549 cases and 1,492 controls. We additionally examined associations with more aggressive PCa (defined as regional/distant stage, elevated Gleason score or prostate-specific antigen level).

RESULTS Compared with <1/week, there was a positive association with PCa risk for intake ?1/week of French fries (OR?=?1.37; 95% CI, 1.11–1.69), fried chicken (OR?=?1.30; 95% CI, 1.04–1.62), fried fish (OR?=?1.32; 95% CI, 1.05–1.66), and doughnuts (OR?=?1.35; 95% CI, 1.11–1.66). There was no association for snack chips (OR?=?1.08; 95% CI, 0.89–1.32). Most of the estimates were slightly stronger for more aggressive disease (OR?=?1.41; 95% CI, 1.04–1.92 for fried fish).

CONCLUSION Regular consumption of select deep-fried foods is associated with increased PCa risk. Whether this risk is specific to deep-fried foods, or whether it represents risk associated with regular intake of foods exposed to high heat and/or other aspects of the Western lifestyle, such as fast food consumption, remains to be determined. Prostate © 2013 Wiley Periodicals, Inc.

 

[Michael Scally MD]

Perdonà S, Bruzzese D, Ferro M, et al. Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy. The Prostate 2013;73(3):227-35. Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy - Perdon[] - 2012 - The Prostate - Wiley Online Library

BACKGROUND Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa.

METHODS One hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18-core first prostate biopsy. The discriminating ability between PCa-negative and PCa-positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined.

RESULTS One hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA?×?100), phi and PCA3 were significantly higher in patients with PCa compared to PCa-negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P???0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs?=?0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this “combined” marker achieved the highest net benefit over the examined range of the threshold probability.

CONCLUSIONS phi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3.

 

[Michael Scally MD]

Gershman B, Shui IM, Stampfer M, et al. Prediagnostic Circulating Sex Hormones Are Not Associated with Mortality for Men with Prostate Cancer. Eur Urol. ScienceDirect.com - European Urology - Prediagnostic Circulating Sex Hormones Are Not Associated with Mortality for Men with Prostate Cancer

BACKGROUND: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa).

OBJECTIVE: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS).

DESIGN, SETTING, AND PARTICIPANTS: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed.

OUTCOME MEASURES AND STATISTICAL ANALYSIS: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality.

RESULTS AND LIMITATIONS: PCa cases were followed for a mean of 12.0+/-4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile.

CONCLUSIONS: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens.