Follow-up Prostate-specific Antigen Research Articles

Variation in Guideline Concordant Active Surveillance Followup in Diverse Urology Practices

We examined the frequency of followup prostate specific antigen testing and prostate biopsy among men treated with active surveillance in theacademic and community urology practices comprising MUSIC (Michigan Urological Surgery Improvement Collaborative). MUSIC is a consortium of 42 practices that maintains a prospective clinical registry with validated clinical data on all patients diagnosed with prostate cancer at participating sites. We identified all patients in MUSIC practices who entered active surveillance and had at least 2 years of continuous followup. After determining the frequency of repeat prostate specific antigen testing and prostate biopsy, we calculated rates of concordance with NCCN Guidelines® recommendations (ie at least 3 prostate specific antigen tests and 1surveillance biopsy) collaborative-wide and across individual practices. We identified 513 patients who entered active surveillance from January 2012 through September 2013 and had at least 2 years of followup. Among the 431 men (84%) who remained on active surveillance for 2 years 132 (30.6%) underwent followup surveillance testing at a frequency that was concordant with NCCN® (National Comprehensive Cancer Network®) recommendations. At the practice level, the median rate of guideline concordant followup was 26.5% (range 10% to 67.5%, p<0.001). Among patients with discordant followup, the absence of followup biopsy was common and not significantly different across practices (median rate 82.0%, p = 0.35). Among diverse community and academic practices in Michigan, there is wide variation in the proportion of men on active surveillance who meet guideline recommendations for followup prostate specific antigen testing and repeat biopsy. These data highlight the need for standardized active surveillance pathways that emphasize the role of repeat surveillance biopsies.

Primary care follow-up of radical prostatectomy patients: A regional New Zealand experience.

BackgroundContemporary recommendations regarding the duration of follow-up after radical prostatectomy (RP) are highly heterogeneous. Protocol-based follow-up schemes have been implemented to facilitate the expeditious identification of patients with recurrence. The aim of this study is to assess the reliability and comfort of general practitioners (GPs) in follow-up of RP.MethodsFollowing institutional ethical approval, we performed a retrospective review in patients undergoing follow-up after RP between January 2004 and December 2010. Patient factors, disease variables, and follow-up prostate specific antigen (PSA) compliance was collected. “Noncompliant” follow-up care was defined as: patients that had not received a PSA for a 14 month period within 5 years of prostatectomy. Patient and disease-based risk factors for noncompliant follow-up were assessed. GPs were also surveyed in their follow-up practice of RP patients, to assess their familiarity in caring for these patients.ResultsIn total, 65 cases were identified that met the inclusion criteria. At 60 months of follow-up, 66% (43/65) of patients had a compliant follow-up regime. For patients with noncompliant follow-up at 60 months, median time of compliance did not differ significantly when assessing preoperative PSA, Gleason sum, extraprostatic extension, or surgical margin status. Of the GPs surveyed, 68% of GPs felt comfortable in follow-up of RP patients. Some 62% of GPs would expect the PSA to be < 0.1 and 25% of GPs would measure the PSA annually.ConclusionOur study identified that follow-up by GPs after RP is insufficient. Accordingly, there is a requirement for formal educational programs if primary care is to take a greater role in follow-up of these patients.

Gleason Score ≤ 6 Prostate Cancer at Radical Prostatectomy: Does a High-Risk Setting Truly Exist? A Recursive Partitioning Analysis

BackgroundThe purpose of this study was to determine whether a “high-risk” subpopulation of low-grade (Gleason score ≤6) prostate cancer defined by lower prostate-specific antigen (PSA) relapse-free survival (bRFS) might be identified within a large population of men who underwent radical prostatectomy (RP) alone, with mature follow-up. Patients and MethodsPatients were retrospectively identified for inclusion by cT1-2 prostate cancer managed with RP alone. Exclusion criteria were: Gleason score ≥7 at RP, any pre- or post-RP radiotherapy or hormone therapy, or PSA follow-up <12 months. The Kaplan–Meier method was used for survival estimates; recursive partitioning by conditional inference analysis was applied to identify variables associated with bRFS. ResultsFrom 2002 through 2010, 284 eligible patients were identified. Median age was 60 years (range, 44-76 years), 233 (82%) were cT1c, and median PSA was 5.3 ng/dL (92% ≤10). The median biopsy to RP interval was 50 days (range, 11-410, with 97% <180 days). Eighty patients (28%) had positive margin (M+). At a median follow-up of 92.6 months (range, 16.9-160.9, with 45% followed ≥ 8 years), 32 patients (11%) had PSA failure, with an estimated 8-year bRFS rate of 89%. In univariate analysis, M+, extraprostatic extension, detectable initial post-RP PSA, and longer biopsy to RP interval were significantly associated with lower bRFS. M+ and longer biopsy to RP interval remained significant in multivariable analysis. Recursive partitioning analysis identified M+ as the only stratification factor, with 8-year bRFS estimates of 74% versus 95% for M+ versus margin-negative. ConclusionGleason score ≤6 prostate cancer managed using RP alone is associated with high rates of bRFS; however, margin positivity predicts early PSA failure rates in >20% of patients.

Gleason grading challenges in the diagnosis of prostate adenocarcinoma: experience of a single institution.

Gleason score (GS) is an important factor in determining management and outcome of prostate adenocarcinoma. A standard GS scheme was introduced by ISUP 2005 consensus conference, but there is still significant discordance in grading prostate adenocarcinomas among pathologists, especially between genitourinary-trained (GU) and non-GU pathologists. All biopsies from outside institutions referred for definitive treatment in our hospital are reviewed by a GU pathologist for confirmation and quality assurance. From 2011 to 2013, 117 consecutive prostate consults were retrieved and compared with the initial outside reports as well as final radical prostatectomy (RP) results. Follow-up prostate specific antigen (PSA) was assessed pre- and post-RP, and the results were analyzed. The overall initial GS was higher for all specimens (p = 0.007) especially for the RP cases (p = 0.002). Overall, the modal GS on initial diagnosis was GS7(4 + 3) that was downgraded to the modal GS6(3 + 3) upon review. Despite an overall substantial agreement between the non-GU and GU pathologists [ICC = 0.66], GS by GU pathologist had higher correlation with the final GS in the RP specimen [ICC = 0.62] than non-GU pathologist [ICC = 0.48]. GS on all reviewed cases were found to correlate significantly with the pre-operative PSA (p = 0.002) but the same was not true for the initial report. A non-GU pathologist is more likely to assign a higher GS than a GU pathologist, with a trend to overcall Gleason pattern 4. Considering the implications on treatment, close attention must be paid to the ISUP 2005 consensus conference recommendations.

Long-Term Efficacy and Toxicity of Low-Dose-Rate 125I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with (125)I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

Sexually transmitted infections, benign prostatic hyperplasia and lower urinary tract symptom-related outcomes: results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

To examine whether a history of sexually transmitted infections (STIs) or positive STI serology is associated with prevalent and incident benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS)-related outcomes in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Self-reported history of STIs (gonorrhoea, syphilis) was ascertained at baseline, and serological evidence of STIs (Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus (HPV)-16, HPV-18, herpes simplex virus type 2, human herpesvirus type 8 and cytomegalovirus) was detected in baseline serum specimens. We used data collected on the baseline questionnaire, as well as results from the baseline prostate-specific antigen (PSA) test and digital rectal examination (DRE), to define prevalent BPH/LUTS-related outcomes as evidence of LUTS (self-reported diagnosis of an enlarged prostate/BPH, BPH surgery or nocturia [waking ≥2 times/night to urinate]) and evidence of prostate enlargement (PSA > 1.4 ng/mL or prostate volume ≥30 mL) in men without prostate cancer. We created a similar definition of incident BPH using data from the follow-up questionnaire completed 5-13 years after enrolment (self-reported diagnosis of an enlarged prostate/BPH or nocturia), data on finasteride use during follow-up, and results from the follow-up PSA tests and DREs. We used Poisson regression with robust variance estimation to calculate prevalence ratios (PRs) in our cross-sectional analysis of self-reported (n = 32 900) and serologically detected STIs (n = 1 143) with prevalent BPH/LUTS, and risk ratios in our prospective analysis of self-reported STIs with incident BPH/LUTS (n = 5 226). Generally null results were observed for associations of a self-reported history of STIs and positive STI serologies with prevalent and incident BPH/LUTS-related outcomes, with the possible exception of T. vaginalis infection. This STI was positively associated with prevalent nocturia (PR 1.36, 95% confidence interval (CI) 1.18-1.65), prevalent large prostate volume (PR 1.21 95% CI 1.02-1.43), and any prevalent BPH/LUTS (PR 1.32 95% CI 1.09-1.61); too few men had information on both STI serologies and incident BPH/LUTS to investigate the associations between T. vaginalis infection and incident BPH/LUTS-related outcomes. Our findings do not support associations of several known STIs with BPH/LUTS-related outcomes, although T. vaginalis infection may warrant further study.

MP86-17 CLINICALLY SIGNIFICANT INCIDENTAL PROSTATE CANCER DETECTED IN RADICAL CYSTOPROSTATECTOMY SPECIMENS

You have accessJournal of UrologyProstate Cancer: Detection and Screening VII1 Apr 2015MP86-17 CLINICALLY SIGNIFICANT INCIDENTAL PROSTATE CANCER DETECTED IN RADICAL CYSTOPROSTATECTOMY SPECIMENS Swar Shah, Soroush Bazaragani, Gus Miranda, Hooman Djaladat, Anne Schuckman, and Siamak Daneshmand Swar ShahSwar Shah More articles by this author , Soroush BazaraganiSoroush Bazaragani More articles by this author , Gus MirandaGus Miranda More articles by this author , Hooman DjaladatHooman Djaladat More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1926AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES While the focus of radical cystoprostatectomy (RC) is usually a bladder-primary malignancy, incidental prostate cancer is a common finding during pathological examination of the surgical specimen. While mostly clinically insignificant and generally minimally monitored, we sought to characterize clinically significant prostate cancer (csPCA), which may require closer monitoring. Herein, we evaluate the role of prostate specific antigen (PSA) in monitoring csPCA diagnosed at the time of RC. METHODS Using and IRB approved prospective database, we identified 1451 patients who underwent RC between 2003 and 2014 at our institution. Clinically significant prostate cancer was defined as Gleason score ≥7, extra prostatic extension, seminal vesicle involvement, positive surgical margin, and lymph node involvement. PSA values were recorded. In patients with evidence of a biochemical recurrence, complete follow up was obtained. Patients were diagnosed with recurrence based on PSA values or findings on cross sectional imaging. RESULTS We identified a total of 107 patients with csPCA diagnosed at the time of RC, of whom 42 had PSA followup. Average age at the time of RC in these patients was 72.24 ± 9.52 years, with a median follow up of 2.18 years. Mean baseline PSA prior to surgery was 4.45±7.49. Two (4.7%) patients developed a recurrence of their prostate cancer, aged 66 and 65 at the time of surgery, and diagnosed 6.8 and 6.1 years after RC. Both had Gleason grade 3+4 on RC pathology, with no capsule penetration, bladder extension, seminal vesicle involvement, or nodal extension. PSA at the time of recurrence was 0.12 and 43.6 each. PSA peaks were 0.52 and 80.6, respectively. The first was diagnosed based on an enlarged lymph node on routine postoperative cross sectional imaging followed by a steady rise in PSA, which was ultimately biopsy proven PCA. He was unable to undergo radiotherapy because his neobladder would not tolerate the doses of radiation required for prostate cancer and refused ADT. The second was diagnosed based on a markedly elevated PSA, and underwent ADT with a normalization of his markers. He had a marker relapse 3 years after cessation of ADT. Both were alive at last follow up, 6.9 and 9.5 years post-surgery. CONCLUSIONS Less than 5% of patients develop a relapse after diagnosis of csPCA on RC pathology. The relative paucity of recurrence makes it difficult to establish parameters for monitoring, however time to diagnosis (>6 years) suggests long term-follow up in these patients may be necessary to monitor for recurrence. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1082 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Swar Shah More articles by this author Soroush Bazaragani More articles by this author Gus Miranda More articles by this author Hooman Djaladat More articles by this author Anne Schuckman More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Contemporary Use of Initial Active Surveillance Among Men in Michigan with Low-risk Prostate Cancer

BackgroundActive surveillance (AS) has been proposed as an effective strategy to reduce overtreatment among men with lower risk prostate cancers. However, historical rates of initial surveillance are low (4–20%), and little is known about its application among community-based urology practices. ObjectiveTo describe contemporary utilization of AS among a population-based sample of men with low-risk prostate cancer. Design, setting, and participantsWe performed a prospective cohort study of men with low-risk prostate cancer managed by urologists participating in the Michigan Urological Surgery Improvement Collaborative (MUSIC). Outcome measurements and statistical analysisThe principal outcome was receipt of AS as initial management for low-risk prostate cancer including the frequency of follow-up prostate-specific antigen (PSA) testing, prostate biopsy, and local therapy. We examined variation in the use of surveillance according to patient characteristics and across MUSIC practices. Finally, we used claims data to validate treatment classification in the MUSIC registry. Results and limitationsWe identified 682 low-risk patients from 17 MUSIC practices. Overall, 49% of men underwent initial AS. Use of initial surveillance varied widely across practices (27–80%; p=0.005), even after accounting for differences in patient characteristics. Among men undergoing initial surveillance with at least 12 mo of follow-up, PSA testing was common (85%), whereas repeat biopsy was performed in only one-third of patients. There was excellent agreement between treatment assignments in the MUSIC registry and claims data (κ=0.93). Limitations include unknown treatment for 8% of men with low-risk cancer. ConclusionsHalf of men in Michigan with low-risk prostate cancer receive initial AS. Because this proportion is much higher than reported previously, our findings suggest growing acceptance of this strategy for reducing overtreatment. Patient summaryWe examined the use of initial active surveillance for the management of men with low-risk prostate cancer across the state of Michigan. We found that initial surveillance is used much more commonly than previously reported, but the likelihood of a patient being placed on surveillance depends strongly on where he is treated.

Definition of Biochemical Success Following Primary Whole Gland Prostate Cryoablation

We identified an evidence-based definition of biochemical success following primary whole gland prostate cryoablation. The COLD Registry was queried for a risk stratified cohort of otherwise treatment naïve patients who underwent primary whole gland prostate cryoablation, of whom none had received any type of adjuvant therapy. Minimum followup in all study patients was 5 years. Variables included patient age, prostate specific antigen at diagnosis, Gleason score, D'Amico risk category and followup prostate specific antigen. Biochemical progression-free survival was studied based on Kaplan-Meier results using the Phoenix definition. HRs were calculated using proc PHReg. Of 1,111 patients 891 achieved nadir prostate specific antigen less than 0.4 ng/ml, which correlated with a 5-year biochemical progression-free survival rate of 90.4% in those at low risk, 81.1% in those at intermediate risk and 73.6% in those at high risk. Nadir prostate specific antigen 0.4 ng/ml or greater wasassociated with 24-month biochemical failure of 29.2% in those at low risk, 46.4% in those at intermediate risk and 48.9% in those at high risk. Statistical analysis failed to reveal a superior prostate specific antigen end point compared to 0.4 ng/ml. HR findings supported the relevance of the end point of less than 0.4ng/ml (p <0.0001). To our knowledge this study represents the first evidence-based definition of biochemical success after primary whole gland prostate cryoablation. Nadir prostate specific antigen less than 0.4 ng/ml was the best objective indicator of biochemical success. Nadir prostate specific antigen 0.4 ng/ml or greater was associated with less favorable biochemical progression, precluding the use of a higher nadir prostate specific antigen end point (HR 5.649, 95% CI 4.33-7.38, p <0.0001).

Practice Patterns of Urologists in Managing Korean Men Aged 40 Years or Younger With High Serum Prostate-specific Antigen Levels

To investigate the practice patterns of urologists in managing Korean men aged 40 years or younger with high serum prostate-specific antigen (PSA). Data were collected from general health screenings conducted at 4 university hospitals between 2004 and 2012. Eligibility criteria were Korean men aged≤40 years who were seen by urologists for high PSA (>2.5 ng/mL). After excluding individuals with chronic prostatitis and any infectious symptoms and/or signs, the practice patterns of urologists managing 237 eligible men were analyzed. The most common practice was observation after antibiotics (40.5%), followed by reassurance (38.4%), prostate biopsy (PBx) after antibiotics (11.8%), PBx after PSA follow-up (7.6%), and immediate PBx (1.7%). Antibiotics were prescribed empirically to 124 patients (52.3%). Of the entire patients, 145 of 237 (61.2%) had at least 1 follow-up PSA, and the follow-up PSA with median interval of 43 days (interquartile range, 26-149) was higher than initial PSA in 66 of 145 (45.5%). Of the 98 patients undergoing follow-up PSA after initial antibiotic treatment, 53 (54.1%) experienced a decline in PSA, whereas 45 (45.9%) experienced a rise in PSA. PBx was performed in 50 of 237 (21.1%), and only a single case (2%) of prostate cancer was diagnosed. In managing men≤40 years with high PSA, the most common practice pattern was observation after antibiotic treatment despite lack of evidences. Furthermore, 1 in 5 urologists performed PBx to rule out cancer. Given the very low prevalence of cancer in this age group, clear guidelines are needed for appropriate management and consistency of care.

Prostate-Specific Antigen Bounce Following Stereotactic Body Radiation Therapy for Prostate Cancer

Introduction: Prostate-specific antigen (PSA) bounce after brachytherapy has been well-documented. This phenomenon has also been identified in patients undergoing stereotactic body radiation therapy (SBRT). While the parameters that predict PSA bounce have been extensively studied in prostate brachytherapy patients, this study is the first to analyze the clinical and pathologic predictors of PSA bounce in prostate SBRT patients.Materials and Methods: Our institution has maintained a prospective database of patients undergoing SBRT for prostate cancer since 2006. Our study population includes patients between May 2006 and November 2011 who have at least 18 months of follow-up. All patients were treated using the CyberKnife treatment system. The prescription dose was 35–36.25 Gy in five fractions.Results: One hundred twenty patients were included in our study. Median PSA follow-up was 24 months (range 18–78 months). Thirty-four (28%) patients had a PSA bounce. The median time to PSA bounce was 9 months, and the median bounce size was 0.50 ng/mL. On univariate analysis, only younger age (p = 0.011) was shown to be associated with an increased incidence of PSA bounce. Other patient factors, including race, prostate size, prior treatment by hormones, and family history of prostate cancer, did not predict PSA bounces. None of the tumor characteristics studied, including Gleason score, pre-treatment PSA, T-stage, or risk classification by NCCN guidelines, were associated with increased incidence of PSA bounces. Younger age was the only statistically significant predictor of PSA bounce on multivariate analysis (OR = 0.937, p = 0.009).Conclusion: PSA bounce, which has been reported after prostate brachytherapy, is also seen in a significant percentage of patients after CyberKnife SBRT. Close observation rather than biopsy can be considered for these patients. Younger age was the only factor that predicted PSA bounce.

Preoperative Androgen Deprivation Therapy for Localized Prostate Cancer: Delayed Biochemical Recurrence in High-Risk Disease

BackgroundThe role of preoperative ADT for localized prostate cancer is controversial; prospective assessments have yielded varying results. We sought to define a subset of patients with a higher likelihood of benefit from preoperative ADT. Patients and MethodsAn institutional database including consecutive patients receiving definitive surgery for localized prostate cancer was interrogated. Patients recorded as having received preoperative ADT were matched in a 1:2 fashion to patients who had not received previous ADT. Patients were matched on the basis of clinicopathologic characteristics, use of adjuvant treatment strategies, and duration of prostate-specific antigen follow-up. Time to biochemical recurrence (TTBR) was compared using the Kaplan-Meier method and log-rank test for the overall study population and in subsets defined according to D'Amico risk. ResultsNo significant differences in clinicopathologic characteristics were noted between recipients (n = 101) and matched nonrecipients (n = 196) of preoperative ADT. Although not statistically significant, positive surgical margin rates, seminal vesicle invasion, and extracapsular extension were less frequent in patients receiving preoperative ADT. Furthermore, a lesser incidence of perioperative complications was noted in this group (7.4% vs. 18.4%). No significant differences were noted in TTBR between recipients and nonrecipients of preoperative ADT in the overall study population. However, among patients with high-risk disease, TTBR was significantly longer in patients who had received preoperative ADT (P = .004). ConclusionThe data presented herein suggest a potential benefit of preoperative ADT in patients with high-risk localized prostate cancer. Consideration should be given to enriching for this subset in preoperative studies of novel endocrine therapies.

Interval to biochemical recurrence following radical prostatectomy does not affect survival in men with low-risk prostate cancer

To evaluate the temporal relationship between interval to biochemical recurrence (BCR) following radical prostatectomy (RP) and prostate cancer-specific mortality (PCSM). The study comprised of 2,116 men from the Victorian Radical Prostatectomy Register, a whole-of-population database of all RPs performed between 1995 and 2000 in Victoria, Australia. Follow-up prostate-specific antigen and death data were obtained via record linkage to pathology laboratories and the Victorian Registry of Births, Deaths and Marriages. Poisson regression models with PCSM as the outcome were fit to the data. Models included age at surgery, Gleason score and tumour stage as covariates. Median post-surgery and post-BCR follow-up was 10.3 and 7.5 years, respectively. 695 men (33 %) experienced BCR during follow-up, of which 82 % occurred within 5 years of RP; 66 men died from prostate cancer. Men with combined high Gleason sum (≥4 + 3) and extra-prostatic (≥pT3a) disease had substantially increased mortality rate with early BCR, while those experiencing BCR after a longer interval had significantly lower mortality. Men with combined low Gleason sum (≤3 + 4) and organ-confined disease (≤pT2c) risk disease were not at any substantial risk of death in this time frame regardless of timing of BCR following RP. This study evaluates the temporal relationship between BCR and PCSM using a whole-of-population cohort of men treated with RP. Men with low-risk features of prostate cancer at time of RP have low mortality even if they experience early BCR. This subgroup may be counselled regarding their favourable long-term prognosis.

The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients

Background:Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa.Methods:Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes.Results:Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on ‘low- and intermediate-recurrence risk' PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients' age.Conclusion:The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients.

The impact of reducing the frequency of prostate specific antigen (PSA) testing among men on active surveillance for prostate cancer.

5092 Background: Active surveillance is a management strategy for men with low risk prostate cancer. Most surveillance regimens include routine PSA assessments, typically performed q 3 mos, although recent studies have questioned the utility of short-term PSA kinetics. Moreover, frequent PSA assessments may be associated with repeated intervals of anxiety around the time of testing, decreasing overall quality of life and potentially leading to avoidable interventions. We hypothesized that PSA assessment q 6 mos rather than q 3 mos would yield similar PSA kinetics calculations. Methods: We analyzed data from the Prostate Active Surveillance Study (PASS), a prospective, multicenter cohort accruing data and biospecimens from men on surveillance at 9 sites across North America. In PASS, PSAs are measured q 3 mos, with high completeness of data. We included data from men who had at least 5 PSA assessments after diagnosis, separated by ≥6 months (most had 10 PSAs separated by 3 months). PSA doubling time (PSADT) was calculated as ln(2) divided by the slope of a regression line drawn through the 5 PSAs. PSADT3 and PSADT6 were defined as the PSADT calculated from q 3 mos and q 6 mos data, respectively; for PSADT6, PSAs between each 6-month measurement were ignored. In each case, PSADT of 0-3 years defined progression, and PSADT &gt; 3 years or declining PSA defined non-progression. Results: 161 men had sufficient PSA followup for analysis. 133 had no progression by either PSADT3 or PSADT6, and 16 progressed by both PSADT calculations. 4 and 8 men, respectively, progressed only by the PSADT3 or PSADT6 calculation but not by the other calculation. The κ score for agreement of progression ascertainment between PSADT3 and PSADT6 was 0.68, and McNemar’s test indicated no statistically significant difference between the two assessments (p=0.39). Conclusions: Calculating PSADT using 6-month rather than 3-month PSA assessments does not significantly change ascertainment of PSA progression in men on surveillance. Our finding suggests that surveillance protocols may reduce the frequency of PSA testing, potentially reducing unnecessary biopsy procedures and patient anxiety due to more frequent PSA measurements.

Galectin-3: a possible complementary marker to the PSA blood test.

The prostate-specific antigen (PSA) test has served as a blood marker of prostate cancer (PCa), and for monitoring recurrence/metastasis in patients after therapeutic intervention. However, the applicability/reliability of the PSA test was recently questioned as it is not without challenges, in particular in men who have PCa without an elevated PSA (false negative), or in men who are disease-free with elevated levels of PSA (false positive). Galectin-3 is a tumor-associated protein; present in the seminal fluid and is a substrate for the PSA enzyme e.g., a chymotrypsin-like serine protease. We hypothesized that the cleavage status and level of galectin-3 in the prostate tissue and sera are associated with PCa. Thus, we compared galectin-3 levels obtained from sera of non-cancer urology patients to those of metastatic PCa patients. The data were confirmed by analyzing PCa tissue arrays. Here, we report that galectin-3 levels in the sera of patients with metastatic PCa were uniformly higher as compared to the non-cancer patient controls. The data suggest that galectin-3 serum level may be a useful serum complementary marker to the PSA blood test to be used for initial and follow-up PSA complimentary diagnostic/prognostic tool for recurrence in PCa patients.

Is there a withdrawal syndrome with abiraterone acetate (AA)?

89 Background: The withdrawal syndrome phenomenon in prostate cancer is defined as a subset of patients (pts) who experience decreasing prostate-specific antigen (PSA) values with or without clinical improvement from the withdrawal of androgen receptor (AR) inhibitors or steroids used as endocrine therapies in castration-resistant prostate cancer (CRPC). In view of its steroidal backbone and structural similarity to progesterone, abiraterone acetate (AA) might act as an AR agonist in certain subsets of CRPC. So far, this phenomenon has not been reported with AA. The aim of this study was to assess the incidence and clinical meaning of such a PSA decrease in pts after AA discontinuation Methods: A retrospective review of 218 consecutive pts treated with AA for metastatic CRPC received after docetaxel between 01/2009 and 08/2012 was conducted in two French centers. PSA values were evaluated before, during and at the end of AA treatment. We retrospectively collected PSA values performed after AA discontinuation (at 4 weeks) and until further treatment or death. Pts were typically kept on prednisone at AA discontinuation. Results: Amongst 218 consecutive patients, 66 pts (30%) were assessed for PSA follow-up after AA discontinuation; reasons for no assessment were mostly: immediate chemotherapy (13%), death (21%); ongoing AA (23%), non evaluated (14%). Amongst the 66 pts, AA therapy was associated with a PSA decrease in 65% pts. Median AA treatment duration was 5.1 months[1.5-39.9]. Twenty-one out of 66 pts (32%) had a PSA decrease when measured at AA disruption and 4 weeks afterwards. The median PSA decrease was 19% [3-68%]. A PSA decrease of greater than 50% was observed in 4 pts (19%). The median duration before progression was 5.5 weeks [1.7-54]. Two of the 4 pts with a PSA decrease&gt;50% exhibited clinical benefit. PSA decrease duration in the 4 pts was7.1 wks [1.1-11.5]. Conclusions: A serum PSA decrease occurred in 32% of pts after AA discontinuation. PSA decrease greater than 50% was observed in 6% of pts with a potential clinical benefit. This event was usually of minor magnitude and short-term. Physiopathological explanations for this observation remain unclear and may be related to the direct activity of AA on the AR.

Potential Consequences of Low Biopsy Core Number in Selection of Patients With Prostate Cancer for Current Active Surveillance Protocols

To compare the performance of the Epstein criteria and the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria in the identification of patients eligible for active surveillance (AS) but treated with radical prostatectomy. We evaluated the baseline characteristics, final pathologic examination, and prostate-specific antigen follow-up (median 43 months, range 1-118) in a series of 492 consecutive patients with prostate cancer managed by radical prostatectomy without AS from 2001 to 2011 at a single institution. Using the postoperative histologic findings, multivariate analysis was used to identify the preoperative predictors of unfavorable AS selection (Gleason score >6 and/or greater than stage pT2c on the final pathologic examination). Biochemical recurrence-free survival was compared between favorably and unfavorably selected patients. Applying the Epstein and PRIAS criteria, 29.2% and 32.2% of the patients had Gleason score >6 or stage pT3 on final pathologic examination, respectively. After a median follow-up of 35.5 and 38 months, 4.2% and 4.3% of patients developed biochemical recurrence in the Epstein and PRIAS criteria groups, respectively. Patients with unfavorable selection had significantly worse biochemical recurrence-free survival than patients with favorable selection (P<.05). Although the median biopsy core number was 8, a biopsy core number<9 was a significant and independent predictor for unfavorable preoperative AS selection in the PRIAS group. We found a non-negligible risk of underestimating unfavorable cancer in patients theoretically qualifying for AS in our cohort. The current use of a sufficient number of biopsy cores might improve the selection process for AS.

Prostate-specific antigen spikes with 131Cs brachytherapy. Is there a difference with other radioisotopes?

There is a suggestion that a dose-rate effect exists for the prostate-specific antigen (PSA) spike after brachytherapy. ¹³¹Cs is a newer radioisotope with a half-life of 9.7 days that is being used for prostate brachytherapy. There is no published data on the PSA spike with this radioisotope and the goal of this study was to quantify PSA spikes with ¹³¹Cs and compare it with published data for other isotopes. We have been maintaining a prospective database for all patients treated with ¹³¹Cs prostate brachytherapy at our institution. We selected patients for whom followup PSA was available for at least 24 months. The PSA spike was defined as an increase of 0.2 ng/mL, followed by a decline to prespike level. One hundred twenty-three patients had monotherapy, whereas 32 had external beam radiation therapy followed by a brachytherapy boost. Median followup was 36 months and mean numbers of PSAs obtained were 7. Forty-six (29.7%) patients had a PSA spike. The mean time and duration for the PSA spike were 12.5 and 8.8 months, respectively. The mean magnitude of increase and mean PSA value at increase were 0.63 and 1.56 ng/mL, respectively. The incidence of a PSA spike in our series is consistent with reported numbers for other radioisotopes. The occurrence of the spike at 12.5 months appears to be at the early end of the spectrum reported for (125)I, but the duration and magnitude are similar to other radioisotopes.

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound-guided biopsy results). Phoenix PFS rates at 1, 2, and 3 years were 100%, 100%, and 71.4%. 73%, respectively; achieved PSA nadir of <0.5 ng/mL; and 47% of patients had a nadir of <0.1 ng/mL. Treatment-related toxicity was minimal, with no operative interventions, fistulas, or other grade ≥3 gastrointestinal (GI)/genitourinary (GU) toxicity. Thirteen percent had grade 1 GI and 33% had grade 2 GU toxicities. Postsalvage, 20% of patients had no erectile dysfunction, 67% of patients had medication-responsive erectile dysfunction, and 13% of patients had erectile dysfunction refractory to medication. Focal psPPI with MR-planning in highly selected patients is feasible with short-term control comparable to conventional salvage, with less toxicity. Longer follow-up is needed to confirm its impact on quality of life and treatment.