• May 13, 2013 – 22:38

    Latest Update on Prostate Cancer Screening at the AUA Meeting, May 2013

    At the American Urological Association Annual Meeting earlier this week, new guidelines from the AUA now recommend that men aged 55 to 69 who are considering prostate cancer screening discuss the benefits and potential harms of screening with their doctors, then to proceed based upon personal values and preferences.  This recommendation is based upon high-quality evidence that suggests the screening benefit over 2- to 4-year intervals would allow 1 man per 1,000 to avert death from prostate cancer over a decade, yet the benefit extrapolated over a man's lifetime may actually be greater. 

    The AUA guidelines state that screening for prostate cancer in men less than 40 years of age is not recommended, nor is routine screening in men 40 to 54 years of age at average risk.  To reduce harms of screening, a screening interval of 2 years may be preferable over annual screening in low-risk men who have engaged in shared-decision making with their physician.  Lastly, routine prostate cancer screening in men over 70, or in men with a less than 10- to 15-year life expectancy is not recommended.

    Reference: American Urological Association Annual Meeting, May 4-8, 2013, San Diego, California, USA

  • May 1, 2013 – 14:01

    Personalized PSA Testing May Reduce Prostate Biopsies

    Recent studies have identified genetic variants associated with increased PSA levels and prostate cancer risk, raising the possibility of diagnostic bias.  By correcting for these variants, it has been postulated that a “personalized” cut-off for PSA levels could be determined which could help to better stratify patients for prostate biopsy to rule out cancer.  Genetic correction of PSA was performed by dividing a subject's PSA value by his combined genetic risk. 

    Four single nucleotide polymorphisms associated with PSA levels have been identified in healthy subjects without prostate cancer.  Genetic correlation of PSA results in 964 Caucasian men was associated with a significantly decreased percentage of men reaching biopsy thresholds, estimating a 15% to 20% relative reduction in biopsies using a threshold of 2.5ng/ml or greater or 4.0ng/ml or greater, respectively.  In addition, genetic correlation could results in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses.

    Limitations of this study include a small cohort of only Caucasian men, suggesting the need for a larger study across various ethnicities.  The influence of genetic correction on clinical outcomes requires further prospective study in a large, independent cohort.  Lastly, the applicability of cost-effectiveness must be considered, since genetic testing may not be readily available across practices.

    Reference: Helfand BT, Loeb S, Hu Q, et al.  Personalized prostate specific antigen testing using genetic variants may reduce unnecessary prostate biopsies.  J Urol 2013;189:1697-1701.

  • December 16, 2012 – 19:59

    Using MRI to Validate Scoring System for Prostate Cancer

    Until recently, wide variations in acquisition protocols and the lack of robust diagnostic criteria make magnetic resonance imaging (MRI) detection of prostate cancer (PCa) one of the most challenging fields in radiology and urology.  A recent trial sought to validate the recently proposed European Society of Urogenital Radiology (ESUR) scoring system for multiparametric MRI (mpMRI) of the prostate, taking advantage of the development of MRI/transrectal ultrasonography (TRUS) fusion technology to evaluate the predictive values of the ESUR scoring system in a cohort of 129 consecutive patients with a total of 1514 cores.

    A prospective study from May to November 2011, 129 consecutive patients with a history of negative TRUS-guided biopsies of the prostate were referred for repeat biopsies. A total of 129 consecutive patients (mean age: 64.7 ± 6.9 yr [range: 47–79]) were enrolled for repeat biopsies (mean number of prior biopsy sessions: 1.3 ± 0.7 [range: 1–4]). Digital rectal examination (DRE) was unremarkable in 107 patients and suspicious in 22 patients (nodule smaller than half a lobe). Mean prostate-specific antigen (PSA) at biopsy was 9.6 ± 5.9 ng/ml (range: 2.7–40.0), and prostate volume (MRI estimate) was 51.1 ± 28.1 cm3 (range: 12–192).  A threshold of ESUR-S (EUR Score Sum) ≥ 9 exhibited the following characteristics: sensitivity: 73.5%; specificity: 81.5%; positive predictive value: 38.2%; negative predictive value: 95.2%; and accuracy: 80.4%.

    Although this trial was not designed to compare repeat biopsy strategies, more targeted cores than random systematic cores were found to be positive for cancer (36.3% compared with 4.9%, p < 0.00001).  Given the inherent challenges of choosing patients for repeat biopsy, the ESUR scoring system was shown to provide clinically relevant stratification of the risk of showing PCa in a given location.  Although the ESUR system was based on literature evidence and consensus, it still lacked validation in a real-life setting.  Only a few cancers were detected solely by random core biopsy specimens, as opposed to the larger yield of cores targeted at mpMRI-suspicious locations.  The validation of the ESUR scoring system and precise targeting of TRUS-guided biopsies now provide convincing leverage in the challenging field of PCa diagnosis.

    Reference: Portalez D, Mozur P, Cornud F, et al.  Validation of the European Society of Urogenital Radiology Scoring System for Prostate Cancer Diagnosis on Multiparametric Magnetic Resonance Imaging in a Cohort of Repeat Biopsy Patients.  Eur J Urol 2012;62:986-996.

  • September 28, 2012 – 11:24

    Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy

    Since the causative link between prostate cancer and androgen dependence was first highlighted in 1941, androgen deprivation has been the mainstay of treatment for men with metastatic prostate disease. Recently, the NCIC Clinical Trials Group convened a phase 3 trial with a primary end point of overall survival to investigate intermittent versus continuous androgen deprivation in men with rising PSA levels after radiotherapy and no evidence of metastatic disease.

    This trial enrolled 1386 men, of whom 690 were randomly assigned to intermittent therapy and 696 to continuous therapy with a mean follow-up of 6.9 years.  In the intermittent therapy group, 35% of men experienced full testosterone recovery, with potential benefits regarding physical function, fatigue, urinary problems, hot flashes, decreased libido, and erectile function.  Median overall survival was 8.8 years and 9.1 years in the intermittent- and continuous-therapy groups, respectively (hazard ratio for death = 1.02).

    Intermittent androgen deprivation was found to be non-inferior (nearly comparable) to continuous therapy with respect to overall survival in men with metastatic prostate cancer.  The authors concluded that this trial raised several provocative issues in that the non-significant increase in deaths from other causes among patients in the continuous-therapy group could not be attributed to any specific non-toxic effects.  However, the cost savings from reduction in drug use in the intermittent-therapy group could have been partially offset by the closer follow-up.  While an intermittent approach to androgen deprivation does not necessarily yield inferior survival, some benefits in quality of life were observed.

    Reference: Crook JM, O'Callaghan CJ, Duncan G, et al.  Intermittent androgen suppression for rising PSA level after radiotherapy.  NEJM 2012;367:895-903.

  • August 23, 2012 – 11:06

    Identifying Men for Active Surveillance in Prostate Cancer

    Since the PSA assay hit the mainstream for prostate cancer screening in the late 1980's, detection of prostate cancer has allowed for various levels of stratification for treatment, including active surveillance.  This modality for prostate cancer treatment has not been widely adopted based upon the imprecision of the risk status based upon TRUS-guided prostate biopsy. 

    A recent trial examined 124 men with favorable risk prostate cancer who were assigned to active surveillance.  The trial sought to describe the extent to which repeat TRUS biopsy can detect and rule out clinically relevant prostate cancer in men with favorable risk cancer.

    In this trial, repeat TRUS biopsy failed to detect 80% of clinically relevant cancers, with a negative predictive value of 23-60%.  The authors state that from this unique study, their data will allow clinicians to discuss conservative approaches for presumed favorable risk prostate cancer.  Importantly, the imprecision of testing and biopsy may be directly related to the choice of active surveillance. 

    The authors conclude that in patients to be considered for active surveillance, they should undergo template guided perineal prostate biopsies, since this modality is more likely to detect cancer than TRUS biopsies.  Ultimately, there may be a selection bias for diagnosis of higher volume disease if a larger number of biopsies overlap and sample the cancerous lesion more than once, which would provide a false-positive result.

    Reference: Barzell WE, Melamed MR, Cathcart P, et al.  Identifying candidates for active surveillance: an evaluation of the repeat biopsy strategy for men with favorable risk prostate cancer.  Journal of Urology 2012;188:762-768.

  • July 15, 2012 – 07:07

    Survival Benefit of Radical Prostatectomy in Patients with Localized Prostate Cancer

    With the advent of new prostate cancer screening guidelines from the United States Preventive Services Task Force (USPSTF; http://www.uspreventiveservicestaskforce.org/prostatecancerscreening.htm) the debate continues with regard to active versus surveillance treatment for localized prostate cancer.  To date, only 1 randomized trial has compared radical prostatectomy to active surveillance.

    This trial reviewed the records of 44,694 patients treated with radical prostatectomy versus observation between 1992 and 2005 in the SEER (Surveillance, Epidemiology, and End Results)-Medicare database.  The number needed to treat to prevent a single adverse outcome ranged from 29 to 34 across the various Charlson comorbidity indices.  The 10-year cancer-specific mortality rate in men treated with radical prostatectomy versus observation was 5.2% compared to 12.8% for high risk prostate cancer, and 1.4% versus 3.8% for low to intermediate risk prostate cancer. 

    The authors of this trial conclude that men with high risk prostate cancer gain the largest survival benefit with radical prostatectomy, while the lowest benefit was observed in men with low to intermediate risk prostate cancer.  Given that this was observational data, the results may have been attributable to treatment bias.  Similar to previous trials, men who received active treatment longer than 6 months after diagnosis were placed in the observation group.  In most cases, prostate-specific antigen (PSA) values were not available, thus subjects could not be stratified by this measurement.

    Reference: Abdollah F, Sun M, Schmitges J, et al.  Survival benefit of radical prostatectomy in patients with localized prostate cancer: estimations of the number needed to treat according to tumor and patient characteristics.  J Urol 2012;188:73-83.

  • June 25, 2012 – 15:41

    Colonoscopy Prevents Colorectal Cancer Deaths

    Colorectal cancer is the third most common cancer and the fifth leading cause of cancer death in men worldwide.  The majority of colorectal cancers arise from adenomatous polyps, which can be detected with screening colonoscopy.  Previously, the investigators of the National Polyp Study (NPS), found that colorectal cancer can be prevented by colonoscopic removal of adenomatous polyps.  However, it has been unclear if the cancers prevented were those that had the potential to cause death.  Recently, Zauber and colleagues reported* the effect of colonoscopic polypectomy on mortality from colorectal cancer.  The researchers conducted a long-term prospective  study of the NPS cohort of patients to determine the mortality among patients with adenomas removed compared with the expected mortality from colorectal cancer in the general  population.   The death rate of patients with adenomas was also compared with an internal control group of patients with nonadenomatous polyps.  Among 2,602 patients who had adenomas removed, 12 died from colorectal cancer over a median  period 15.8 years, compared with 25 expected deaths in the general population, suggesting a 53% reduction in mortality.  Mortality from colorectal cancer among patients with adenomatous polyps was similar to those with nonadenomatous during the first 10 years after polypectomy.  Thereafter, mortality increased for patients with adenomas, when strict surveillance was not organized by the study’s investigators.  The researchers concede several limitations of the study.  A small number of skilled endoscopists performed the colonoscopies, thus the observations may not be applicable to a community practice, for which the reported rates of colorectal cancer after polypectomy are higher than those reported in the NPS.  The results of the study may not be  representative of the general population, since the study was not a randomized, controlled trial.  In conclusion, the study’s findings further support the belief that colonoscopic removal of adenomatous polyps prevents colorectal cancer death.  The results also underscore the importance of longterm-term surveillance for patients after the initial removal of adenomatous polyps.  More randomized, population-based trials are necessary to determine the effectiveness of screening colonoscopy  on colorectal cancer mortality.

    Reference: Zauber AG, et al. Colonoscopic Polypectomy and Long-Term Prevention of Colorectal-Cancer Deaths. N Engl J Med 2012;366:687-96.                                                                                                                           

    Bretthauer M, Kalager M.  Colonoscopy as a triage screening test. N Engl J Med 2012;366:759-60.

  • February 25, 2012 – 15:02

    Prostate Cancer Screening Does Not Improve Mortality

    The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a multi-center, randomized trial aimed at determining disease-specific mortality outcomes.  The goal relative to prostate cancer was to determine if a reduction in prostate cancer mortality would occur through screening via PSA and DRE.  A recent manuscript summary reported data 13 years in follow-up after the trial.

    Nearly 77,000 men ages 55-74 years were randomly assigned to either screening via PSA screening for 6 years and DRE for 4 years versus usual care, which included “opportunistic screening”.  At 13 years, 4250 men were diagnosed with prostate cancer in the screening group versus 3815 in the control group.  Cumulative data discovered a 12% increase in prostate cancer incidence in the screening group, yet mortality in the intervention and control groups were 3.7 and 3.4/10,000 person/years, respectively (relative risk = 1.09).  There was a non-statistically significant decrease in incidence of high-grade prostate cancer in the intervention screening group.

    This data suggests that no mortality benefit was observed for routine screening for prostate cancer via PSA and DRE after 13 years of follow-up.  In contrast, the European Randomized Study for Prostate Cancer (ERSPC) trial published in the New England Journal of Medicine in 2009 reported a 20% reduction in prostate cancer mortality after 10 years of follow-up in men ages 55-69.  However, in the PLCO trial, 45% of men had at least one PSA in the 3 years prior to randomization, while 52% of men had a PSA during the screening period; the rate of screening in the control group was approximately 50% that of the intervention group.  The authors state that they plan to update this data after 15 years of total follow-up.  Lastly, they suggest caution in determining efficacy of prostate cancer screening as their results demonstrate the effect of adding regular screening in addition to opportunistic screening , as to date, there is no evidence of benefit.

    Reference: Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up.  J Natl Cancer Inst 2012;104:1-8.

  • February 7, 2012 – 13:43

    Models predicting erectile function after treatment for localized prostate cancer

    Management of localized prostate cancer aims at achieving the trifecta of cancer control, urinary continence, and preservation of erectile function. With optimal cancer control being achieved through most interventions, the focus is currently on the other two outcomes that form a major quality of life issue in these men who are expected to be cured of their primary disease.

    Pre-treatment prediction of post-intervention erectile function would be useful in patient counseling. The Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) is a prospective, multicenter study that in 2003, began enrolling men with localized prostate cancer scheduled for definitive therapy with radical prostatectomy, external beam radiotherapy or brachytherapy.  Apart from baseline patient data, the investigators recorded details of the treatment planned including nerve sparing surgery, hormonal therapy and radiation protocols. Post-intervention patient reported outcomes were recorded by third-party interviews using validated questionnaires.

    In a recent trial by Alemozaffar and colleagues published in JAMA, the study investigators reported patient assessed erectile function in 1027 men who had completed 24 months after intervention. A significant increase in erectile dysfunction was reported in all 3 intervention groups: 63% vs 28% in radical prostatectomy, 63% vs 47% in the external radiotherapy group and 57% vs 33% in the brachytherapy group. Among men who were potent prior to intervention, 52% had ED after intervention; 60% in the prostatectomy group, 42% in the external radiotherapy group and 37% in the brachytherapy group. The authors were able to generate models that accurately predicted the occurrence of erectile dysfunction in the three treatment strategies.  Models such as this one suggest that stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer.  While such a model cannot be used to judge superiority of one treatment strategy over another, it does aid in counseling patients about their individual outcome probabilities.

    Alemozaffar M, Regan MM, Cooperberg MR, Wei JT, et al. Prediction of erectile function following treatment for prostate cancer.  JAMA 2011;306:1205-14.

  • October 25, 2011 – 12:23

    Prostate Cancer Screening Guidelines – DEBATE !!!

    Last week, the United States Preventive Services Task Force (USPSTF) released a statement that it will downgrade its recommendation for prostate cancer screening.  The previous recommendation from August 2008 states “the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years”.  The USPSTF now recommends prostate cancer screening via the serum prostate-specific antigen (PSA) test, in asymptomatic men because evidence indicates that the harms of the test outweigh its benefits.

     This statement has received significant media attention in the United States and in Europe, and is felt to be very controversial.  The American Urological Association (AUA) responded immediately to the USPSTF's statement, citing “the task force’s recommendations will ultimately do more harm than good to the many men at risk for prostate cancer, both here in the US and around the world.  Until there is a better widespread test for this potentially devastating disease, the USPSTF — by disparaging the test — is doing a great disservice to the men worldwide who may benefit from the PSA test” (AUA Daily Scope, October 13, 2011)./