Prostate ...

[MR10X]

My urologist wants to put me back on ADT since my test levels are back to normal,he says there might be microscopic PCa still there. My oncologist and endo dont have a problem with my levels being normal.My last blood work was TT 493 (348-1197) FT 4.7 (6.6-18.1) and my LH was high 16.1 (1.7-8.6).I dont understand why my LH is so high unless your HTPA senses FT and not TT.I was on the LHRHa for 6 months and i had all those side effects and felt absolutely horrible.I have been off the ADT for a year now. MY last PSA was 0.60 with normal TT levels...

 

[Michael Scally MD]

My urologist wants to put me back on ADT since my test levels are back to normal,he says there might be microscopic PCa still there. My oncologist and endo dont have a problem with my levels being normal.My last blood work was TT 493 (348-1197) FT 4.7 (6.6-18.1) and my LH was high 16.1 (1.7-8.6).I dont understand why my LH is so high unless your HTPA senses FT and not TT.I was on the LHRHa for 6 months and i had all those side effects and felt absolutely horrible.I have been off the ADT for a year now. MY last PSA was 0.60 with normal TT levels...

I agree. While not entirely familiar with the case, the TT is NO reason to begin ADT.

 

[Michael Scally MD]

Controversies in Prostate Cancer

http://www.med.unc.edu/urology/advances-in-urology-symposium/controversies-in-prostate-cancer-walsh-presentation

 

[Michael Scally MD]

Testosterone Serum Levels and Prostate Cancer Prognosis: The Double Face of Janus

[Another nail in the coffin that AAS cause Prostate Cancer! It would NOT surprise me if AAS are found to be protective.]

It is actually clear that the long-held belief that high serum androgen concentrations increase the PCa risk can no longer be supported.

These studies suggest that PCas are stimulated to dedifferentiate in a testosterone-deficient environment, leading to more aggressive tumors.

Longer survival was observed for patients with serum testosterone above median compared with below median.

The mechanisms by which more elevated serum testosterone seems to select less-aggressive tumor clones in the castration-resistant state, however, are not clear.

However, it is not clear why higher testosterone levels, although associated with a greater overall survival, seemed to be predictive of lower abiraterone efficacy over prednisone.

In conclusion, the role of serum testosterone in the modulation of PCa growth is complex and the molecular alterations favoring a more indolent disease course in the presence of higher serum testosterone levels in both in hormone-naive and castrate-resistant patients needs to be elucidated and is an exciting field for future research.

Valcamonico F, Ferrari L, Consoli F, Amoroso V, Berruti A. Testosterone serum levels and prostate cancer prognosis: the double face of Janus. Future Oncol 2014;10(7):1113-5. http://www.futuremedicine.com/doi/full/10.2217/fon.14.1

 

[MR10X]

http://www.ncbi.nlm.nih.gov/pubmed/16875775?dopt=Abstract

 

[Michael Scally MD]

[NO INCREASE] Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy

Haider A, Zitzmann M, Doros G, Isbarn H, Hammerer P, Yassin A. Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from Five Year-median Follow-up of Three Registries. J Urol. http://www.jurology.com/article/S0022-5347(14)03885-3/abstract

BACKGROUND: Although there is no evidence that testosterone (T) therapy increases risk of prostate cancer (PCa), there is a paucity of long-term data.

OBJECTIVE: To determine whether incidence of PCa is increased in hypogonadal men receiving long-term T therapy.

DESIGN, SETTING, AND PARTICIPANTS: In three parallel, prospective, ongoing, cumulative registry studies, 1,023 hypogonadal men received T therapy. Two study cohorts were treated by urologists (since 2004), one by an academic andrology centre (since 1996).

Patients were treated when total testosterone was </=12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism present. Maximal follow-up was 17 years (1996 to 2013), median follow-up five years. Mean baseline patient age in the urological settings was 58 years, in the andrology setting 41 years.

INTERVENTION(S): Patients received T undecanoate injections in 12-week-intervals. Pre-treatment examination of the prostate and monitoring during treatment were performed. Prostate biopsies were performed according to EAU Guidelines.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Numbers of positive and negative biopsies were assessed. Incidence of PCa and post-prostatectomy outcomes were studied.

RESULTS AND LIMITATIONS: A total of 11 patients were diagnosed with PCa in the two urology settings with proportions of 2.3% and 1.5%, respectively. Incidence per 10,000 patient years was 54.4 and 30.7, respectively. No PCa was reported in the Andrology Centre. Limitations are inherent in the registry design without control group.

CONCLUSIONS: T therapy in hypogonadal men does not increase the risk of PCa. If guidelines for T therapy are properly applied, T treatment is safe in hypogonadal men.

 

[Michael Scally MD]

Mathew P. The bifunctional role of steroid hormones: implications for therapy in prostate cancer. Oncology (Williston Park) 2014;28(5):397-404. http://www.cancernetwork.com/oncology-journal/bifunctional-role-steroid-hormones-implications-therapy-prostate-cancer

Ablation of the androgen-signaling axis is currently a dominant theme in developmental therapeutics in prostate cancer. Highly potent inhibitors of androgen biosynthesis and androgen receptor (AR) function have formally improved survival in castration-resistant metastatic disease. Resistance to androgen-ablative strategies arises through diverse mechanisms. Strategies to preserve and extend the success of hormonal therapy while mitigating the emergence of resistance have long been of interest.

In preclinical models, intermittent hormonal ablative strategies delay the emergence of resistant stem-cell-driven phenotypes, but clinical studies in hormone-naive disease have not observed more than noninferiority over continual androgen ablation.

In castration-resistant disease, response and improvement in subjective quality of life with therapeutic testosterone has been observed, but so too has symptomatic and life-threatening disease acceleration.

The multifunctional and paradoxical role of steroid hormones in regulating proliferation and differentiation, as well as cell death, requires deeper understanding. The lack of molecular biomarkers that predict the outcome of hormone supplementation in a particular clinical context remains an obstacle to individualized therapy.

Biphasic patterns of response to hormones are identifiable in vitro, and endocrine-regulated neoplasms that proliferate after prolonged periods of hormone deprivation appear preferentially sex steroid-suppressible. This review examines the relevance of a translational framework for studying therapeutic androgens in prostate cancer.

 

[Michael Scally MD]

Morgentaler A. New concepts regarding testosterone and prostate cancer: a breath of fresh air. Oncology (Williston Park) 2014;28(5):404-5. http://www.cancernetwork.com/oncology-journal/new-concepts-regarding-testosterone-and-prostate-cancer-breath-fresh-air

After a quarter of a century struggling to decipher what is true and untrue about prostate cancer (PCa) and androgens, the review by Paul Mathew in this issue of ONCOLOGY comes as a breath of fresh air. What a pleasure to read a new perspective on a problem that has been bedeviled by rigid ideas developed more than 70 years ago, like flies fixed in amber!

Evidence soon accumulated that none of the basic tenets of the androgen hypothesis were correct. High levels of serum testosterone or dihydrotestosterone are not associated with increased risk of PCa. Androgen deprivation does reduce PSA levels, but raising serum testosterone well into the supraphysiologic range for months in otherwise healthy men has been shown to have no effect on mean PSA level or prostate volume.

The explanation for this, termed the saturation model, is that the ability of testosterone to stimulate PCa growth is finite, with maximal stimulation occurring at fairly low serum testosterone concentrations, in the range of 250 ng/dL. Thus, the “high testosterone is risky for prostate cancer development” part of the androgen hypothesis also has proved incorrect.

What about the concept that administering androgens to a man with prostate cancer will universally cause rapid growth?

In 2011, my colleagues at Baylor College of Medicine and I reported on 13 men with untreated PCa, on active surveillance, who received testosterone therapy for a mean of 2.5 years. There was no increase in mean PSA level, or in prostate volume. No man demonstrated cancer progression—and all men reported subjective improvement in symptoms.

Our more recent single-center experience at Men’s Health Boston with a larger group of 33 men was presented at the annual meeting of the American Urological Association in 2013, with similar reassuring results. These results support the validity of the saturation model.

If none of the tenets of androgen hypothesis orthodoxy are correct, then what are we left with?

Dr. Mathew takes us several steps down this new path. Whereas the primary thrust of the last 7 decades of research into treatment of advanced prostate cancer has been to find ways to more completely deprive PCa of androgen, Dr. Mathew asks a completely different question: Are there ways in which testosterone administration may be beneficial?

Basic science and a number of clinical experiences have suggested for years that steroid hormones may have bifunctional roles, as Dr. Mathew puts it. As the androgen hypothesis finally fades from prominence, now is an excellent time to shake the sleep from our eyes, breathe in the fresh air, and look again at a world of new possibilities.

 

[MR10X]

My PSA level 6 months after implants and radiation treatment was 0.09.After 3 months of TRT of 120 mg of test E my PSA was 0.60,which my oncologist said was still low and had no problem with my Test levels being normal.This was over a year after my treatments...My TT level on 120 mg Test E was 1580 3 days after my last shot..I have since discontinued the TRT and my TT level just tested was 493,my last Test shot was Jan 13th,last blood work was June.

 

[Michael Scally MD]

Prostate Cancer Settings in Which Testosterone May Function as a Tumor Suppressor
http://www.cancernetwork.com/oncology-journal/bifunctional-role-steroid-hormones-implications-therapy-prostate-cancer

 

[Michael Scally MD]

[NO BENEFIT] Fifteen-Year Survival Outcomes Following Primary Androgen-Deprivation Therapy for Localized Prostate Cancer

Lu-Yao GL, Albertsen PC, Moore DF, et al. Fifteen-Year Survival Outcomes Following Primary Androgen-Deprivation Therapy for Localized Prostate Cancer. JAMA Intern Med. Published online July 14, 2014. http://archinte.jamanetwork.com/article.aspx?articleid=1887061

Importance One in 6 American men will be diagnosed as having prostate cancer during their lifetime. Although there are no data to support the use of primary androgen-deprivation therapy (ADT) for early-stage prostate cancer, primary ADT has been widely used for localized prostate cancer, especially among older patients.

Objective To determine the long-term survival impact of primary ADT in older men with localized (T1/T2) prostate cancer.

Design, Setting, and Participants This was a population-based cohort study of 66 717 Medicare patients 66 years or older diagnosed from 1992 through 2009 who received no definitive local therapy within 180 days of prostate cancer diagnosis. The study was conducted in predefined US geographical areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program. Instrumental variable analysis was used to assess the impact of primary ADT and control for potential biases associated with unmeasured confounding variables. The instrumental variable comprised combined health services areas with various usage rates of primary ADT. The analysis compared survival outcomes in the top tertile areas with those in the bottom tertile areas.

Main Outcomes and Measures Prostate cancer–specific survival and overall survival.

Results With a median follow-up of 110 months, primary ADT was not associated with improved 15-year overall or prostate cancer–specific survival following the diagnosis of localized prostate cancer. Among patients with moderately differentiated cancers, the 15-year overall survival was 20.0% in areas with high primary ADT use vs 20.8% in areas with low use (difference: 95% CI, −2.2% to 0.4%), and the 15-year prostate cancer survival was 90.6% in both high- and low-use areas (difference: 95% CI, −1.1% to 1.2%). Among patients with poorly differentiated cancers, the 15-year cancer-specific survival was 78.6% in high-use areas vs 78.5%, in low-use areas (difference: 95% CI, −1.8% to 2.4%), and the 15-year overall survival was 8.6% in high-use areas vs 9.2% in low-use areas (difference: 95% CI, −1.5% to 0.4%).

Conclusions and Relevance Primary ADT is not associated with improved long-term overall or disease-specific survival for men with localized prostate cancer. Primary ADT should be used only to palliate symptoms of disease or prevent imminent symptoms associated with disease progression.

 

[Michael Scally MD]

Dupree JM, Langille GM, Khera M, Lipshultz LI. The safety of testosterone supplementation therapy in prostate cancer. Nat Rev Urol;advance online publication. http://www.nature.com/nrurol/journal/vaop/ncurrent/full/nrurol.2014.163.html

Patients with prostate cancer can present with hypogonadism and experience health and quality-of-life declines related to low testosterone levels.

Despite generations of urological dogma suggesting that testosterone supplementation therapy (TST) for hypogonadism causes prostate-cancer progression, a review of the contemporary literature provides evidence to the contrary.

The prostate saturation model suggests that the androgen receptor (AR) is saturated at serum testosterone levels of 150-200 ng/dl, and that additional serum testosterone above this level has limited, if any, effects within the prostate.

Indeed, studies in the modern era of PSA assessments indicate that TST does not affect prostate size, intraprostatic testosterone levels, or prostate-cancer progression, provided the baseline serum testosterone level is greater than this AR saturation point.

However, the body of data on this subject comes from a small number of cases, and TST should only be administered to patients with prostate cancer after thorough discussions of the risks and benefits, with subsequent careful monitoring.

 

[Michael Scally MD]

San Francisco IF, Rojas PA, DeWolf WC, Morgentaler A. Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance. BJU International 2014;114(2):229-35. http://onlinelibrary.wiley.com/doi/10.1111/bju.12682/full

Objective To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS).

Patients and Methods Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver–operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan–Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis.

Results A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25–14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification.

Conclusions Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

 

[Michael Scally MD]

Dalal K, Roshan-Moniri M, Sharma A, et al. Selectively Targeting the DNA Binding Domain of the Androgen Receptor as a Prospective Therapy for Prostate Cancer. J Biol Chem. http://www.jbc.org/content/early/2014/08/01/jbc.M114.553818.long

The Androgen Receptor (AR) is a transcription factor that has a pivotal role in the occurrence and progression of prostate cancer (PCa).

The AR is activated by androgens that bind to its ligand-binding domain (LBD), causing the transcription factor to enter the nucleus and interact with genes via its conserved DNA-binding domain (DBD).

Treatment for PCa involves reducing androgen production or using anti-androgen drugs to block the interaction of hormones with the AR-LBD. Eventually the disease changes into a castration resistant form (CRPC) where LBD mutations render anti-androgens ineffective or where constitutively active AR splice variants, lacking the LBD, become over-expressed.

Recently, we identified a surfaced exposed pocket on the AR-DBD as an alternative drug-target site for AR inhibition. Here, we demonstrate that small molecules designed to selectively bind the pocket effectively block transcriptional activity of full-length and splice variant AR forms at low- to sub- muM concentrations. The inhibition is lost when residues involved in drug interactions are mutated.

Furthermore, the compounds did not impede nuclear localization of the AR and blocked interactions with chromatin, indicating the interference of DNA binding with the nuclear form of the transcription factor. Finally, we demonstrate the inhibition of gene expression and tumor volume in mouse xenografts.

Our results indicate that the AR-DBD has a surface site that can be targeted to inhibit all forms of the AR, including Enzalutamide resistant and constitutively active splice variants and thus may serve as a potential avenue for the treatment of recurrent and metastatic prostate cancer.

http://www.jbc.org/content/early/2014/08/01/jbc.M114.553818.long

 

[Michael Scally MD]

Balbontin FG, Moreno SA, Bley E, Chacon R, Silva A, Morgentaler A. Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer. BJU International 2014;114(1):125-30. http://onlinelibrary.wiley.com/doi/10.1111/bju.12668/full


Objective To evaluate the clinical and biochemical effects of long-acting testosterone undecanoate injections in men with prostate cancer treated with brachytherapy, as the use of testosterone therapy (TTh) in men with prostate cancer is highly controversial, with limited published safety data, particularly after brachytherapy treatment.

Patients and Methods In all, 20 men treated with brachytherapy for prostate cancer received TTh for symptoms of testosterone deficiency from February 2005 to August 2013. Symptoms of testosterone deficiency included low libido, erectile dysfunction, and fatigue. The mode of TTh was long-acting testosterone undecanoate injections in all cases. Sexual function was assessed by Sexual Health Inventory for Men (SHIM) questionnaire. Serum PSA and testosterone concentrations were recorded monthly for 3 months, then every 3 months for the first year, every 6 months for the second year, and annually then after.

Results The mean (range) age was 62 (49–74) years and the mean (range) serum PSA level at the time of prostate cancer diagnosis was 6.2 (2–11.5) ng/mL. The Gleason score was 2 + 3 in one patient, 3 + 3 in 15 patients, 3 + 4 in three patients and 4 + 4 in one patient. In all, 15 men were stage T1c and five were T2a. The mean (range) baseline total testosterone concentration was 343 (200–592) ng/dL, and 6.9 (2.1–9.7) ng/dL for free testosterone. The mean SHIM scores improved with treatment from 16.1 at baseline to 22.1 with TTh (P = 0.002). There was a decrease in mean PSA level from baseline of 0.7 ng/mL before initiation of TTh to 0.1 ng/mL at last follow-up (P < 0.001), with a median (range) follow-up of 31 (12–48) months. There were no cases of prostate cancer progression or recurrence.

Conclusions With a median of 31-months follow-up, long-acting testosterone injections in men with prostate cancer treated with brachytherapy produced significant clinical benefits. There were no cases of rising serum PSA, prostate cancer progression or recurrence.

 

[Michael Scally MD]

PSA Test Is Misused, Unreliable, Says the Antigen's Discoverer
http://www.medscape.com/viewarticle/828854

n this edition of Medscape One-on-One, host and Medscape Editor-in-Chief Eric J. Topol, MD, interviews Richard J. Ablin, PhD, DSc (Hon), who first discovered prostate-specific antigen (PSA) in 1970.

At the time, Dr. Ablin and colleagues were trying to identify an antigen that was specific to prostate cancer. What Dr. Ablin identified instead was that PSA was present not only in malignant prostates but also in benign prostates.

He did agree, however, that elevated levels of PSA might be useful in predicting a recurrence of prostate cancer in men who were thought to be in remission.

It was much to Dr. Ablin's dismay that more than 2 decades later, in the mid-1990s, the US Food and Drug Administration (FDA) approved the use of PSA not only to test for recurrence of cancer, but also as a possible predictor of cancer.

Since then, Dr. Ablin maintains, the United States spends billions each year administering a preventive prostate cancer screening test to men, using PSA, that produces false positives in the majority of cases.

In his interview with Dr. Topol, Dr. Ablin explains why physicians and patients should proceed with caution when using PSA as a marker for preventive screening.

 

[Michael Scally MD]

Preston MA, Wilson KM, Markt SC, et al. 5α-Reductase Inhibitors and Risk of High-Grade or Lethal Prostate Cancer. JAMA Intern Med. 2014;174(8):1301-1307. http://archinte.jamanetwork.com/article.aspx?articleid=1878668

Importance 5α-Reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear.

Objective To determine the association between 5ARI use and development of high-grade or lethal prostate cancer.

Design, Setting, and Participants Prospective observational study of 38 058 men followed up for prostate cancer diagnosis and outcomes between 1996 and 2010 in the Health Professionals Follow-up Study.

Exposures Use of 5ARIs between 1996 and 2010.

Main Outcomes and Measures Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing.

Results During 448 803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high grade (Gleason sum [GS] 8-10), 1238 were GS 7, and 1600 were low grade (GS 2-6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After adjusting for confounders, men who reported ever using 5ARIs over the study period had a reduced risk of overall prostate cancer (hazard ratio

---

, 0.77; 95% CI, 0.65-0.91). 5ARI users had a reduced risk of GS 7 (HR, 0.67; 95% CI, 0.49-0.91) and low-grade (GS 2-6) prostate cancer (HR, 0.74; 95% CI, 0.57-0.95). 5ARI use was not associated with risk of high-grade (GS 8-10) prostate cancer (HR, 0.97; 95% CI, 0.64-1.46) or lethal disease (HR, 0.99; 95% CI, 0.58-1.69). Increased duration of use was associated with significantly lower risk of overall prostate cancer (HR for 1 year of additional use, 0.95; 95% CI, 0.92-0.99), localized (HR, 0.95; 95% CI, 0.90-1.00), and low-grade disease (HR, 0.92; 95% CI, 0.85-0.99). There was no association for lethal, high-grade, or grade 7 disease.

Conclusions and Relevance While 5ARI use was not associated with developing high-grade or lethal prostate cancer, it was associated with a reduction in low-grade, GS 7, and overall prostate cancer. Because the number of patients with high-grade or lethal prostate cancer in our cohort was limited, we cannot rule out potential risk of harm with 5ARI use.

 

[Michael Scally MD]

Ankerst DP, Hoefler J, Bock S, et al. Prostate Cancer Prevention Trial risk calculator 2.0 for the prediction of low- vs high-grade prostate cancer. Urology 2014;83(6):1362-7. http://www.goldjournal.net/article/S0090-4295(14)00249-0/abstract

OBJECTIVE: To modify the Prostate Cancer Prevention Trial risk calculator (PCPTRC) to predict low- vs high-grade (Gleason grade>/=7) prostate cancer and incorporate percent free-prostate-specific antigen (PSA).

METHODS: Data from 6664 Prostate Cancer Prevention Trial placebo arm biopsies (5826 individuals), where prostate-specific antigen and digital rectal examination results were available within 1 year before the biopsy and PSA was </=10 ng/mL, were used to develop a nominal logistic regression model to predict the risk of no vs low-grade (Gleason grade<7) vs high-grade cancer (Gleason grade>/=7). Percent free-PSA was incorporated into the model based on likelihood ratio analysis of a San Antonio Biomarkers of Risk cohort. Models were externally validated on 10 Prostate Biopsy Collaborative Group cohorts and 1 Early Detection Research Network reference set.

RESULTS: Of all the Prostate Cancer Prevention Trial biopsies, 5468 (82.1%) were negative for prostate cancer, 942 (14.1%) detected low-grade, and 254 (3.8%) detected high-grade disease. Significant predictors were (log base 2) PSA (odds ratio for low-grade vs no cancer, 1.29*; high-grade vs no cancer, 2.02*; high-grade vs low-grade cancer, 1.57*), digital rectal examination (0.96, 1.49*, 1.55*, respectively), age (1.02*, 1.05*, 1.03*, respectively), African American race (1.13, 2.83*, 2.51*, respectively), prior biopsy (0.63*, 0.81, 1.27, respectively), and family history (1.31*, 1.25, 0.95, respectively), where * indicates P value<.05. The new PCPTRC 2.0 either with or without percent free-PSA (also significant by the likelihood ratio method) validated well externally.

CONCLUSION: By differentiating the risk of low- vs high-grade disease on biopsy, PCPTRC 2.0 better enables physician-patient counseling concerning whether to proceed to biopsy.

 

[Michael Scally MD]

Individualized Risk Assessment of Prostate Cancer
http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp

The original Prostate Cancer Prevention Trial (PCPT) Prostate Cancer Risk Calculator (PCPTRC) posted in 2006 was developed based upon 5519 men in the placebo group of the Prostate Cancer Prevention Trial. All of these 5519 men initially had a prostate-specific antigen (PSA) value less than or equal to 3.0 ng/ml and were followed for seven years with annual PSA and digital rectal examination (DRE). If PSA exceeded 4.0 ng/ml or if an abnormal DRE was noted, a biopsy was recommended. After seven years, all men were recommended to have a prostate biopsy, regardless of PSA or DRE findings. PSA, family history, DRE findings, and history of a prior negative prostate biopsy provided independent predictive value to the calculation of risk of a biopsy that showed presence of cancer.

In 2012, the updated PCPTRC 2.0 was released with the added capability to provide prediction of low-grade (Gleason grade < 7) versus high-grade prostate cancer via a new more user-friendly display of results. PCPTRC 2.0 was based on re-analysis of an expanded set of 6664 biopsies from 5826 patients from the PCPT placebo arm. Characteristics of the patients and biopsies forming PCPTRC 2.0 are similar to those used for the original PCPTRC, but the new PCPTRC 2.0 generally provides lower risk estimates due to the inclusion of multiple prior negative biopsies per individual rather than just one biopsy per person. The original PCPTRC is still available for research purposes on the right hand side of the calculator page, along with prior updates for incorporating other markers for prostate cancer.

The results of the PCPTRC may not apply to different groups of individuals. As about 80% of men had a prostate biopsy with six cores, if more than six cores are obtained at biopsy, a greater risk of cancer may be expected. Most men in this study were white and results may be different with other ethnicities or races.

The calculator is in principle only applicable to men under the following restrictions:

· Age 55 or older
· No previous diagnosis of prostate cancer
· DRE and PSA results less than 1 year old

The PCPTRC is applicable for men who are undergoing prostate cancer screening with PSA and DRE as it was derived from a group of men in the PCPT who underwent annual PSA and DRE screening. The risk estimate from the calculator does not reflect an endorsement of either PSA or DRE for screening for prostate cancer. This calculator is designed to provide a preliminary assessment of risk of prostate cancer if a prostate biopsy is performed. Additional clinical information may modify this risk. No specific level of risk is recommended for prostate biopsy and this decision should be an individual choice based upon a physician-patient relationship.

 

[MR10X]

I had a biopsy done when my PSA was 11.4.They took 12 samples which is now the new amount they use for biopsies. The whole biopsy was pretty much painless and done in the doctors office,i wouldnt have a problem having another one done if needed.