Prostate ...

[Michael Scally MD]

De Nunzio C, Lombardo R, Leonardo C, et al. Serum levels of 17-beta-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort. Urol Oncol. ScienceDirect.com - Urologic Oncology: Seminars and Original Investigations - Serum levels of 17-?-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort

OBJECTIVES: To explore the association between serum levels of 17-beta-estradiol (17BE) and prostate cancer (PCa) risk in men undergoing prostate biopsy.

METHODS AND MATERIALS: Between 2006 and 2012, we prospectively enrolled 894 patients, with no history of PCa, undergoing prostate biopsy. Before biopsy was performed, general data, digital rectal examination (DRE), body mass index, 17BE, and prostate-specific antigen (PSA) were recorded. The risk of detecting cancer and high-grade cancer was assessed as a function of 17BE using crude and adjusted logistic regressions.

RESULTS: Serum levels of 17BE were not associated with an increased risk of PCa or high-grade disease. Age (odds ratio [OR] 1.05; 95% confidence interval [CI]: 1.03-1.07; P = 0.000), DRE(OR 2.81; 95% CI: 1.98-4.00; P = 0.000), and PSA(OR 1.07; 95% CI: 1.04-1.10; P = 0.000) were found to be independent predictors of PCa risk. Age (OR 1.05; 95% CI: 1.01-1.09; P = 0.007), DRE (OR 3.04; 95% CI: 1.79-5.17; P = 0.000), body mass index (OR 1.07; 95% CI: 1.01-1.150; P = 0.040), and PSA (OR 1.08; 95% CI: 1.03-1.12; P = 0.000) were found to be independent predictors of high-grade disease.

CONCLUSION: In our cohort of patients, serum levels of 17BE are not predictive of PCa or high-grade disease. In patients at risk of PCa, 17BE should not be considered a reliable marker to predict poorly differentiated PCa in the setting of initial prostate biopsy.

 

[BBC3]

I understand that Durestaride just about has a "black box" warning as it apparently increases the odds of more aggressive forms of PC. I could not find anything myself other than this general Wiki description. I did not research studies heavily, but NOTABLY, nothing popped up in Google search...??!!!???

And I really think that the below is out of context or misunderstood by the author, as from what i heard its causing more aggresive TYPEs and not more matured cancers at finding (which is what this precludes). I could be mis-informed though..?

Observed in practiceThe FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer.[6] While the potential for positive, negative or neutral changes to the potential risk of developing prostate cancer with dutasteride has not been established, evidence has suggested it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer. The primary area for concern is for patients who may develop prostate cancer whilst taking dutasteride for benign prostatic hyperplasia, which in turn could delay diagnosis and early treatment of the prostate cancer, thereby potentially increasing the risk of these patients developing high-grade prostate cancer.[7]

 

[Michael Scally MD]

Hessels D, Schalken JA. Urinary biomarkers for prostate cancer: a review. Asian J Androl. http://www.nature.com/aja/journal/vaop/ncurrent/full/aja20136a.html

Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection, one of its main drawbacks is its lack of specificity. As a consequence, many men undergo unnecessary biopsies or treatments for indolent tumours. PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour. Since PCa is a heterogeneous disease, a panel of tumour markers is fundamental for a more precise diagnosis. Several biomarkers are promising due to their specificity for the disease in tissue. However, tissue is unsuitable as a possible screening tool. Since urine can be easily obtained in a non-invasive manner, it is a promising substrate for biomarker testing. This article reviews the biomarkers for the non-invasive testing of PCa in urine.

 

[Michael Scally MD]

Zeigler-Johnson C, Morales KH, Spangler E, Chang B-L, Rebbeck TR. Relationship of Early-Onset Baldness to Prostate Cancer in African-American Men. Cancer Epidemiology Biomarkers & Prevention. Relationship of Early-Onset Baldness to Prostate Cancer in African-American Men

Background: Early-onset baldness has been linked to prostate cancer; however, little is known about this relationship in AfricanAmericans who are at elevated prostate cancer risk.

Methods: We recruited 219 African-American controls and 318 African-American prostate cancer cases. We determined age-stratified associations of baldness with prostate cancer occurrence and severity defined by high stage (T3/T4) or high grade (Gleason 7+.) Associations of androgen metabolism genotypes (CYP3A4, CYP3A5, CYP3A43, AR-CAG, SRD5A2 A49T, and SRD5A2 V89L), family history, alcohol intake, and smoking were examined by baldness status and age group by using multivariable logistic regression models.

Results: Baldness was associated with odds of prostate cancer [OR = 1.69; 95% confidence interval (CI), 1.05–2.74]. Frontal baldness was associated with high-stage (OR = 2.61; 95% CI, 1.10–6.18) and high-grade (OR = 2.20; 95% CI, 1.05–4.61) tumors. For men diagnosed less than the age of 60 years, frontal baldness was associated with high stage (OR = 6.51; 95% CI, 2.11–20.06) and high grade (OR = 4.23; 95% CI, 1.47–12.14). We also observed a suggestion of an interaction among smoking, median age, and any baldness (P = 0.02).

Conclusions: We observed significant associations between early-onset baldness and prostate cancer in African-American men. Interactions with age and smoking were suggested in these associations. Studies are needed to investigate the mechanisms influencing the relationship between baldness and prostate cancer in African-American men.

Impact: African-American men present with unique risk factors including baldness patterns that may contribute to prostate cancer disparities.

 

[Michael Scally MD]

Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P. Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee of the American College of Physicians. Annals of Internal Medicine. Annals of Internal Medicine | Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee of the American College of Physicians

Description: Prostate cancer is an important health problem in men. It rarely causes death in men younger than 50 years; most deaths associated with it occur in men older than 75 years. The benefits of screening with the prostate-specific antigen (PSA) test are outweighed by the harms for most men. Prostate cancer never becomes clinically significant in a patient's lifetime in a considerable proportion of men with prostate cancer detected with the PSA test. They will receive no benefit and are subject to substantial harms from the treatment of prostate cancer. The American College of Physicians (ACP) developed this guidance statement for clinicians by assessing current prostate cancer screening guidelines developed by other organizations. ACP believes that it is more valuable to provide clinicians with a rigorous review of available guidelines rather than develop a new guideline on the same topic when several guidelines are available on a topic or when existing guidelines conflict. The purpose of this guidance statement is to critically review available guidelines to help guide internists and other clinicians in making decisions about screening for prostate cancer. The target patient population for this guidance statement is all adult men.

Methods: This guidance statement is derived from an appraisal of available guidelines on screening for prostate cancer. Authors searched the National Guideline Clearinghouse to identify prostate cancer screening guidelines in the United States and selected 4 developed by the American College of Preventive Medicine, American Cancer Society, American Urological Association, and U.S. Preventive Services Task Force. The AGREE II (Appraisal of Guidelines, Research and Evaluation in Europe) instrument was used to evaluate the guidelines.

Guidance Statement 1: ACP recommends that clinicians inform men between the age of 50 and 69 years about the limited potential benefits and substantial harms of screening for prostate cancer. ACP recommends that clinicians base the decision to screen for prostate cancer using the prostate-specific antigen test on the risk for prostate cancer, a discussion of the benefits and harms of screening, the patient's general health and life expectancy, and patient preferences. ACP recommends that clinicians should not screen for prostate cancer using the prostate-specific antigen test in patients who do not express a clear preference for screening.

Guidance Statement 2: ACP recommends that clinicians should not screen for prostate cancer using the prostate-specific antigen test in average-risk men under the age of 50 years, men over the age of 69 years, or men with a life expectancy of less than 10 to 15 years.

 

[zkt]

Does average risk include those on TRT?

 

[Michael Scally MD]

Does average risk include those on TRT?

TRT or for that matter all AAS do NOT increase the risk of Prca.

 

[hackskii]

TRT or for that matter all AAS do NOT increase the risk of Prca.

What about tren, I hear of guys having issues peeing after using tren.
Just curious.

I remember long ago reading a book by a doctor that suggested the treatment for prostate cancer kind of ruined the mans quality of life by needing a diaper, and having ED problems making sex not possible.
He suggested that many men would die of other causes before the prostate ever took them down.

But, it also seems lately that some prostate cancers are more aggressive and in the past took many years to manafest.
I knew a guy that had it for 20 years.

Another guy, chemically castrated him, all kinds of treatments, took the prostate out, had a high PSA with no prostate, then found it on the outside of some bones in his back, then new treatments.
High PSA with no prostate and cancer on his bones?
Crazy

 

[Rostam]

What if someone has an already existing unknown prostate cancer. Would use of AAS or TRT exacerbate the condition?

 

[Michael Scally MD]

What if someone has an already existing unknown prostate cancer. Would use of AAS or TRT exacerbate the condition?

The evidence points to NO.

 

[Michael Scally MD]

Katz MH. Can We Stop Ordering Prostate-Specific Antigen Screening Tests?. JAMA Intern Med. 2013:1-2. JAMA Network | JAMA Internal Medicine | Can We Stop Ordering Prostate-Specific Antigen Screening Tests?Can We Stop Prostate-Specific Antigen Screening?

 

[Michael Scally MD]

Sah S, Elias P, Ariely D. Investigation Momentum: The Relentless Pursuit to Resolve Uncertainty. JAMA Intern Med.2013:1-3. JAMA Network | JAMA Internal Medicine | Investigation Momentum: The Relentless Pursuit to Resolve Uncertainty

Debate regarding the prostate-specific antigen (PSA) screening test centers around test reliability and whether screening reduces mortality. We consider yet another potential downside to the widespread use of unreliable screening tests: the downstream effect of receiving inconclusive or ambiguous results. When receiving information from screening tests, we usually want to know whether the result is a “yes” or a “no.” Receiving an inconclusive result amounts to a “don't know”; this situation should have a level of uncertainty regarding the diagnosis similar to that of not conducting the test at all. Yet, we propose that the psychological uncertainty experienced after an inconclusive test result can lead to investigation momentum: additional, and potentially excessive, diagnostic testing. In contrast, not conducting the unreliable test would result in no further action. To investigate this, we evaluated whether receiving an inconclusive result from an unreliable test (the PSA screening), compared with undergoing no test, motivated more individuals to undertake an additional, more invasive and costly, test (a prostate biopsy).

 

[Michael Scally MD]

Walter LC, Fung KZ, Kirby KA, et al. Five-Year Downstream Outcomes Following Prostate-Specific Antigen Screening in Older Men. JAMA Intern Med. 2013:1-8. JAMA Network | JAMA Internal Medicine | Five-Year Downstream Outcomes Following Prostate-Specific Antigen Screening in Older MenFive-Year Outcomes Following PSA Screening

Importance Despite ongoing controversies surrounding prostate-specific antigen (PSA) screening, many men 65 years or older undergo screening. However, few data exist that quantify the chain of events following screening in clinical practice to better inform decisions.

Objective To quantify 5-year downstream outcomes following a PSA screening result exceeding 4.0 ng/mL in older men.

Design and Setting Longitudinal cohort study in the national Veterans Affairs health care system.

Participants In total, 295 645 men 65 years or older who underwent PSA screening in the Veterans Affairs health care system in 2003 and were followed up for 5 years using national Veterans Affairs and Medicare data.

Main Outcome Measures Among men whose index screening PSA level exceeded 4.0 ng/mL, we determined the number who underwent prostate biopsy, were diagnosed as having prostate cancer, were treated for prostate cancer, and were treated for prostate cancer and were alive at 5 years according to baseline characteristics. Biopsy and treatment complications were also assessed.

Results In total, 25 208 men (8.5%) had an index PSA level exceeding 4.0 ng/mL. During the 5-year follow-up period, 8313 men (33.0%) underwent at least 1 prostate biopsy, and 5220 men (62.8%) who underwent prostate biopsy were diagnosed as having prostate cancer, of whom 4284 (82.1%) were treated for prostate cancer. Performance of prostate biopsy decreased with advancing age and worsening comorbidity (P < .001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men 85 years or older, those with a Charlson-Deyo Comorbidity Index of 3 or higher, and those having low-risk cancer. Among men with biopsy-detected cancer, the risk of death from non–prostate cancer causes increased with advancing age and worsening comorbidity (P < .001). In total, 468 men (5.6%) had complications within 7 days after prostate biopsy. Complications of prostate cancer treatment included new urinary incontinence in 584 men (13.6%) and new erectile dysfunction 588 men (13.7%).

Conclusions and Relevance Performance of prostate biopsy is uncommon in older men with abnormal screening PSA levels and decreases with advancing age and worsening comorbidity. However, once cancer is detected on biopsy, most men undergo immediate treatment regardless of advancing age, worsening comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA screening.

 

[Michael Scally MD]

Bradley LA, Palomaki G, Gutman S, Samson DJ, Aronson N. PCA3 Testing for the Diagnosis and Management of Prostate Cancer [Internet]. PCA3 Testing for the Diagnosis and Management of Prostate Cancer - NCBI Bookshelf

Objectives: - We performed a comparative effectiveness review that examined the use of the prostate cancer antigen 3 (PCA3) gene in improving initial or repeat biopsy decisions in patients identified at risk for prostate cancer, or in improving decisionmaking about treatment choices (e.g., active surveillance vs. aggressive therapy) in patients with prostate cancer positive biopsies. Comparators included total prostate specific antigen (PSA) elevations, free PSA, PSA density, PSA velocity, externally validated nomograms, complexed PSA, and multivariate models.

Data sources: - We searched PubMed® and Embase® from January 1, 1990, to August 8 and August 15, 2011, respectively, and updated through May 15, 2012. We searched the Cochrane Database of Systematic Reviews with no date restriction and updated. A grey literature search included databases with regulatory information, clinical trial registries, abstracts/conference papers, grants and federally funded research, and manufacturer information.

Review methods: - Inclusion criteria required PCA3 and at least one comparator to be measured in the same cohort in one of the three clinical settings: at-risk men considering initial biopsy; at-risk men considering repeat biopsy; and men with prostate cancer making treatment decisions based on risk categorization. Data were extracted by one reviewer and audited by a second. Analyses were matched by comparing within study differences between PCA3 and a comparator. Modeling was used to smooth consensus ROC curves and to address issues relating to verification bias. Diagnostic accuracy studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Strengths of evidence were judged high, moderate, low, or insufficient according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria and the AHRQ “Methods Guide for Medical Test Reviews.”

Results: - After exclusion of six studies with strong likelihood of containing duplicate data, 24 studies provided data that could be used to address diagnostic accuracy (Key Questions [KQ] 1 and 2); 13 studies addressed decisionmaking based on risk stratification criteria (KQ 3). All studies were of poor quality. Comparison of PCA3 to total PSA (tPSA) had the most available studies (22) but was subject to spectrum, verification, and sampling biases; the latter two were addressed in the analyses. We observed that: (1) PCA3 is more discriminatory for detecting cancers (i.e., at any sensitivity, the specificity is higher, or at any specificity, the sensitivity is higher) than tPSA elevations; (2) this finding appears to apply to both initial and repeat biopsies; and (3) PCA3 and tPSA are relatively independent predictors. However, strength of evidence was low. For all other diagnostic accuracy comparisons, and all intermediate and long-term health outcomes, the strength of evidence was insufficient. For treatment decisionmaking in men with positive biopsy, in all comparisons for intermediate and long-term health outcomes, the strength of evidence was found to be insufficient.

Conclusions: - For diagnostic accuracy, there was a low strength of evidence that PCA3 had better diagnostic accuracy for positive biopsy results than tPSA elevations, but insufficient evidence that this led to improved intermediate or long-term health outcomes. For all other settings, comparators, and outcomes, there was insufficient evidence.

 

[Michael Scally MD]

Xia J, Trock BJ, Cooperberg MR, et al. Prostate cancer mortality following active surveillance versus immediate radical prostatectomy. Clin Cancer Res 2013;18(19):5471-8. Prostate Cancer Mortality following Active Surveillance versus Immediate Radical Prostatectomy

PROPOSE: Active surveillance has been endorsed for low-risk prostate cancer, but information about long-term outcomes and comparative effectiveness of active surveillance is lacking. The purpose of this study is to project prostate cancer mortality under active surveillance followed by radical prostatectomy versus under immediate radical prostatectomy.

EXPERIMENTAL DESIGN: A simulation model was developed to combine information on time from diagnosis to treatment under active surveillance and associated disease progression from a Johns Hopkins active surveillance cohort (n = 769), time from radical prostatectomy to recurrence from cases in the CaPSURE database with T-stage </= T2a (n = 3,470), and time from recurrence to prostate cancer death from a T-stage </= T2a Johns Hopkins cohort of patients whose disease recurred after radical prostatectomy (n = 963). Results were projected for a hypothetical cohort aged 40 to 90 years with low-risk prostate cancer (T-stage </= T2a, Gleason score </= 6, and prostate-specific antigen level </= 10 ng/mL).

RESULTS: The model projected that 2.8% of men on active surveillance and 1.6% of men with immediate radical prostatectomy would die of their disease in 20 years. Corresponding lifetime estimates were 3.4% for active surveillance and 2.0% for immediate radical prostatectomy. The average projected increase in life expectancy associated with immediate radical prostatectomy was 1.8 months. On average, the model projected that men on active surveillance would remain free of treatment for an additional 6.4 years relative to men treated immediately.

CONCLUSIONS: Active surveillance is likely to produce a very modest decline in prostate cancer-specific survival among men diagnosed with low-risk prostate cancer but could lead to significant benefits in terms of quality of life.

 

[Michael Scally MD]

AUA RELEASES NEW CLINICAL GUIDELINE ON PROSTATE CANCER SCREENING
http://www.auanet.org/advnews/press_releases/article.cfm?articleNo=290

The guideline makes the following specific statements:

• PSA screening in men under age 40 years is not recommended.
• Routine screening in men between ages 40 to 54 years at average risk is not recommended.
• For men ages 55 to 69 years, the decision to undergo PSA screening involves weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, shared decision-making is recommended for men age 55 to 69 years that are considering PSA screening, and proceeding based on patients’ values and preferences.
• To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision-making and decided on screening. As compared to annual screening, it is expected that screening intervals of two years preserve the majority of the benefits and reduce over diagnosis and false positives.
• Routine PSA screening is not recommended in men over age 70 or any man with less than a 10-15 year life expectancy.

 

[BBC3]

I have read that there are 2-5 (it seems like) prevalent FORMS of PC affecting men.

My Gathering in those reads was that just the same as any other cancer diagnosis, the TYPE cancer is the key. How METASTATIC the cancer it is, and then second probably being the location of the cancer within the prostate. These TWO FACTORS are also related, as certain types of cancers I think are predisposed to forming in certain areas of the prostate.

It seems like I recall a certain form of cancer that develops more centrally and is more NEUROLOGICALLY related, is a NASTY ONE... I could be wrong..

Perhaps a refresher on the TYPEs of cancers diagnosed which I will be happy to attempt to laymanize for review is over due?

Another guy, chemically castrated him, all kinds of treatments, took the prostate out, had a high PSA with no prostate, then found it on the outside of some bones in his back, then new treatments.
High PSA with no prostate and cancer on his bones?
Crazy

 

[Michael Scally MD]

Agent Orange As A Risk Factor For High-Grade Prostate Cancer

Ansbaugh N, Shannon J, Mori M, Farris PE, Garzotto M. Agent Orange as a risk factor for high-grade prostate cancer. Cancer. http://onlinelibrary.wiley.com/doi/10.1002/cncr.27941/abstract

BACKGROUND Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa) (Gleason score ?7) on biopsy in a US Veteran cohort.

METHODS Risk factors included clinicodemographic and laboratory data from veterans who were referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa) (Gleason score ?6) in biopsy specimens. Risk among AOe veterans relative to unexposed veterans was estimated using multivariate logistic regression. Separate models were used to determine whether AOe was associated with an increased risk of PCa, HGPCa, or LGPCa.

RESULTS Of 2720 veterans who underwent biopsy, PCa was diagnosed in 896 veterans (32.9%), and 459 veterans (16.9%) had HGPCa. AOe was associated with a 52% increase in the overall risk of detecting PCa (adjusted odds ratio, 1.52; 95% confidence interval, 1.07-2.13). AOe did not confer an increase in the risk of LGPCa (adjusted odds ratio, 1.24; 95% confidence interval, 0.81-1.91), although a 75% increase in the risk of HGPCa was observed (adjusted odds ratio, 1.75; 95% confidence interval, 1.12-2.74). AOe was associated with a 2.1-fold increase (95% confidence interval, 1.22-3.62; P < .01) in the risk of detecting PCa with a Gleason score ?8.

CONCLUSIONS The current results indicated that an increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men who undergo an initial prostate biopsy. These findings may aid in improved PCa screening for Vietnam-era veterans. Cancer 2013. © 2013 American Cancer Society.

 

[Michael Scally MD]

Gittelman MC, Hertzman B, Bailen J, et al. PCA3 Molecular Urine Test as a Predictor of Repeat Prostate Biopsy Outcome in Men with Previous Negative Biopsies: A Prospective Multicenter Clinical Study. The Journal of urology 2013;190(1):64-9. Elsevier

Purpose - We evaluated the clinical usefulness of the PROGENSA® PCA3 Assay for predicting repeat prostate biopsy outcome.

Materials and Methods - Men with at least 1 prior negative prostate biopsy who were scheduled for repeat prostate biopsy based on best clinical judgment were enrolled at 14 centers. Whole blood and post-digital rectal examination urine samples were collected before extended template transrectal biopsy with 12 or more cores. Urinary PCA3 scores and biopsy outcomes were assessed by logistic regression analysis, which also included age, race, serum prostate specific antigen, clinical stage, family history of prostate cancer and the number of previous negative biopsy sessions.

Results - A total of 466 men were included in study and prostate cancer was identified in 21.9%. A PCA3 score cutoff of 25 yielded 77.5% sensitivity, 57.1% specificity, and negative and positive predictive values of 90% and 33.6%, respectively. On multivariable logistic regression men with a PCA3 score of less than 25 were 4.56 times as likely to have a negative repeat biopsy as men with a score of 25 or greater. PCA3 score significantly increased the predictive accuracy of the logistic regression model. At 90% sensitivity adding the PCA3 score to the model increased specificity, and positive and negative predictive values by 22.6%, 6.4% and 7.1%, respectively, relative to the model without the PCA3 score.

Conclusions - The PCA3 score supplements serum prostate specific antigen and other clinical information to provide more accurate prediction of repeat biopsy outcome. Thus, it provides clinicians and patients with independent, clinically useful information to make more informed repeat biopsy decisions.

 

[Michael Scally MD]

Thelen P, Heinrich E, Bremmer F, Trojan L, Strauss A. Testosterone boosts for treatment of castration resistant prostate cancer: An experimental implementation of intermittent androgen deprivation. The Prostate. http://onlinelibrary.wiley.com/doi/10.1002/pros.22711/abstract

BACKGROUND The primary therapeutic target for non-organ-confined prostate cancer is the androgen receptor (AR). Main strategies to ablate AR function are androgen depletion and direct receptor blockade by AR antagonists. However, incurable castration resistant prostate cancer (CRPC) develops resistance mechanisms to cope with trace amounts of androgen including AR overexpression and mutation in the AR ligand binding domain.

METHODS The CRPC cell model VCaP derivative of a prostate cancer bone metastasis was used in vitro and in nude mice in vivo to examine the effects of immediate testosterone boost on CRPC cells. In addition, a testosterone tolerant cell model was established by incremental acclimatization of VCaP cells to 1?nM testosterone. The effects of androgen withdrawal and testosterone boosts on gene expression were assessed by quantitative real-time polymerase chain reaction, ELISA, and Western blots. Tumor cell proliferation was evaluated with a BrdU test.

RESULTS Testosterone boosts on CRPC VCaP cells eliminate tumor cells to a higher extent than androgen withdrawal in androgen tolerant cells. The pronounced decrease of tumor cell proliferation was accompanied by a marked downregulation of AR expression regarding full-length AR and splice variant AR V7.

CONCLUSIONS Acquiring castration resistance of prostate cancer cells by AR overexpression and amplification obviously sensitizes such cells to testosterone concentrations as low as physiological values. This introduces novel therapeutic means to treat CRPC with non-toxic measures and may find clinical implementation in intermittent androgen deprivation regimens.