Clinical Stage T1c Research Articles

Androgen Deprivation Therapy as Primary Treatment for Prostate Cancer

Hormonal therapy has been the mainstay of treatment for advanced prostate cancer for over 70 yr. The timing and extent of androgen ablative therapy for earlier stage disease remains controversial. In addition, recent studies demonstrate that so-called "castration-resistant" tumors are still dependent on androgen receptor signaling. A 66-yr-old man presented with clinical stage T1C N+ M0 prostate cancer and received primary androgen deprivation therapy. Over the course of the next 17 yr, he was treated with various forms of androgen deprivation therapy, including two newer agents, abiraterone acetate and MDV 3100. A review of the literature was conducted to identify indications, controversies, and new developments regarding hormonal therapy for prostate cancer. Androgen deprivation therapy remains the treatment of choice for metastatic prostate cancer; however, it is not without its adverse effects, and most men with advanced disease eventually develop castration resistance. Newer compounds that more specifically and effectively target androgen and androgen receptor signaling in prostate cancer cells may provide more long-lasting remissions in advanced disease.

High Dose Brachytherapy as Monotherapy for Intermediate Risk Prostate Cancer

We evaluated our retrospective, single institution experience with high dose rate brachytherapy as monotherapy for intermediate risk prostate cancer. Our cohort included 284 patients with intermediate risk prostate cancer, defined as clinical stage T2b/T2c, Gleason score 7 and/or prostate specific antigen 10 to 20 ng/ml, and 1-year minimum followup. Treatment was 2 high dose rate brachytherapy sessions at 3 fractions of 6.5 Gy each for a mean of 19 days. Prostate specific antigen failure was defined as nadir +2 ng/ml. Mean followup was 35.1 months (median 31.9). Actuarial 5-year cause specific survival and clinical local control were 100%, distant-metastasis-free survival 98.8% and biochemical disease-free survival 94.4%. Clinical stage predicted biochemical disease-free survival. For stage T2a or less 5-year biochemical disease-free survival was 95.1% vs 100% for stage T2b and 77.4% for T2c (p = 0.012). Percent positive biopsy cores and prostate specific antigen nadir were also predictive. International Prostate Symptom Score results remained stable and potency was maintained in 82.6% of patients at 2 years. Pads were used for the first time after brachytherapy in 22 patients (7.7%), mostly for grade 1 incontinence (occasionally or less per week). Excluding patients with prior transurethral prostatectomy, stroke or tremor 2.5% used pads for the first time after treatment. No patient had urethral stricture. Radiation Therapy Oncology Group grade 1 rectal toxicity developed in 12 patients (4.2%) but not beyond grade 1. High dose rate brachytherapy as monotherapy is safe and effective for patients with intermediate risk prostate cancer. We recommend caution for percent positive biopsy cores exceeding 75% or clinical stage T2c. Excluding such patients the 5-year biochemical disease-free survival rate was 97.5%.

Multiparametric 3T Prostate Magnetic Resonance Imaging to Detect Cancer: Histopathological Correlation Using Prostatectomy Specimens Processed in Customized Magnetic Resonance Imaging Based Molds

We determined the prostate cancer detection rate of multiparametric magnetic resonance imaging at 3T. Precise one-to-one histopathological correlation with magnetic resonance imaging was possible using prostate magnetic resonance imaging based custom printed specimen molds after radical prostatectomy. This institutional review board approved prospective study included 45 patients (mean age 60.2 years, range 49 to 75) with a mean prostate specific antigen of 6.37 ng/ml (range 2.3 to 23.7) who had biopsy proven prostate cancer (mean Gleason score of 6.7, range 6 to 9). Before prostatectomy all patients underwent prostate magnetic resonance imaging using endorectal and surface coils on a 3T scanner, which included triplane T2-weighted magnetic resonance imaging, apparent diffusion coefficient maps of diffusion weighted magnetic resonance imaging, dynamic contrast enhanced magnetic resonance imaging and spectroscopy. The prostate specimen was whole mount sectioned in a customized mold, allowing geometric alignment to magnetic resonance imaging. Tumors were mapped on magnetic resonance imaging and histopathology. Sensitivity, specificity, positive predictive value and negative predictive value of magnetic resonance imaging for cancer detection were calculated. In addition, the effects of tumor size and Gleason score on the sensitivity of multiparametric magnetic resonance imaging were evaluated. The positive predictive value of multiparametric magnetic resonance imaging to detect prostate cancer was 98%, 98% and 100% in the overall prostate, peripheral zone and central gland, respectively. The sensitivity of magnetic resonance imaging sequences was higher for tumors larger than 5 mm in diameter as well as for those with higher Gleason scores (greater than 7, p <0.05). Prostate magnetic resonance imaging at 3T allows for the detection of prostate cancer. A multiparametric approach increases the predictive power of magnetic resonance imaging for diagnosis. In this study accurate correlation between multiparametric magnetic resonance imaging and histopathology was obtained by the patient specific, magnetic resonance imaging based mold technique.

Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer

Study Type--Prognosis (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Nomograms are available that combine clinical and biopsy findings to predict the probability of pathologically insignificant prostate cancer in patients with clinically low-risk disease. Based on data from patients with Gleason score 6, clinical stage ≤ T2a and PSA <20 ng/ml, our group developed the first nomogram models for predicting insignificant prostate cancer that incorporated clinical data, detailed biopsy data and findings from MRI or MRI/MRSI (BJU Int. 2007;99(4):786-93). When tested retrospectively, these MR models performed significantly better than standard clinical models with and without detailed biopsy data. We prospectively validated the previously published MR-based nomogram models in a population of patients with Gleason score 6, clinical stage ≤ T2a and PSA <10 ng/ml. Based on data from this same population, we also developed two new models for predicting insignificant prostate cancer that combine MR findings and clinical data without detailed biopsy data. Upon initial testing, the new MR models performed significantly better than a clinical model lacking detailed biopsy data. • To validate previously published nomograms for predicting insignificant prostate cancer (PCa) that incorporate clinical data, percentage of biopsy cores positive (%BC+) and magnetic resonance imaging (MRI) or MRI/MR spectroscopic imaging (MRSI) results. • We also designed new nomogram models incorporating magnetic resonance results and clinical data without detailed biopsy data. Nomograms for predicting insignificant PCa can help physicians counsel patients with clinically low-risk disease who are choosing between active surveillance and definitive therapy. • In total, 181 low-risk PCa patients (clinical stage T1c-T2a, prostate-specific antigen level <10 ng/mL, biopsy Gleason score of 6) had MRI/MRSI before surgery. • For MRI and MRI/MRSI, the probability of insignificant PCa was recorded prospectively and independently by two radiologists on a scale from 0 (definitely insignificant) to 3 (definitely significant PCa). • Insignificant PCa was defined on surgical pathology. • There were four models incorporating MRI or MRI/MRSI and clinical data with and without %BC+ that were compared with a base clinical model without %BC and a more comprehensive clinical model with %BC+. Prediction accuracy was assessed using areas under receiver-operator characteristic curves. • At pathology, 27% of patients had insignificant PCa, and the Gleason score was upgraded in 56.4% of patients. • For both readers, all magnetic resonance models performed significantly better than the base clinical model (P ≤ 0.05 for all) and similarly to the more comprehensive clinical model. • Existing models incorporating magnetic resonance data, clinical data and %BC+ for predicting the probability of insignificant PCa were validated. • All MR-inclusive models performed significantly better than the base clinical model.

The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance. Clinical data from two multi-centre European open-label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed. First-catch urine was collected after digital rectal examination (three strokes per lobe) and the PCA3 score was determined using the PROGENSA(®) PCA3 assay. Transrectal ultrasound-guided biopsy (≥8 cores) and radical prostatectomy (RP) specimens were analysed by the local pathologist. The relationship between biopsy and RP outcomes with the PCA3 score was assessed. Of the 1009 men enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were statistically significantly lower in men with biopsy Gleason score <7 vs ≥7, with clinical stage T1c vs T2a-T2c, T3a cancers, with ≤33% vs >33% positive biopsy cores and with 'biopsy indolent' vs 'biopsy significant' prostate cancer (indolent prostate cancer defined by biopsy Epstein criteria). In all, 175 men with a positive biopsy had a RP: median and mean PCA3 scores were statistically significantly lower in men with pathological Gleason score <7 vs ≥7, and with pathological stage T2a-T2c vs T3a-T3b cancers. The PCA3 score may combined with traditional tools aid in identifying men with clinically insignificant prostate cancer, as shown by biopsy and RP pathological features including biopsy Epstein criteria, who could be candidates for active surveillance. Treatment selection should be based on a combination of clinical and pathological variables. If one wants to use a threshold point to guide treatment decisions in clinical practice, a PCA3 score threshold of 20 may have the highest utility for selecting men with clinically insignificant prostate cancer in whom active surveillance may be appropriate; a PCA3 score threshold of 50 may be used to identify men at high risk of harbouring significant prostate cancer who are candidates for RP. Although the association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management strategies may provide clinicians with another tool to more accurately determine the course of treatment.

The Risk of Upstaged Disease Increases with Body Mass Index in Low-Risk Prostate Cancer Patients Eligible for Active Surveillance

Background Obese patients have a greater risk of adverse pathologic features and biochemical recurrence after radical prostatectomy (RP). The impact of body mass index (BMI) on the risk of reclassification and deferred treatment in active surveillance (AS) programs has not been thoroughly assessed. Objective To evaluate the impact of BMI on the risk of reclassification for AS eligibility. Design, setting, and participants We assessed 230 men who underwent an immediate RP and were eligible for AS according to the following criteria: prostate-specific antigen (PSA) ≤10 ng/ml, clinical stage T1c, Gleason score ≤6, fewer than three positive cores, extent of cancer in any core <50%, and life expectancy >10 yr. Intervention All patients underwent a standardised 21-core biopsy and RP at our department between January 2001 and December 2010. Measurements Reclassification was defined as upstaged disease (pathologic stage >pT2) and/or upgraded disease (Gleason score ≥7; primary Gleason pattern 4) in RP specimens. PSA outcomes were also recorded. Results and limitations Mean BMI was 26.4 kg/m 2, and 13% of patients were obese (BMI >30). Mean BMI was the only preoperative factor significantly associated with the risk of upstaged disease. In multivariate analysis, BMI >30 remained an independent predictive factor for upstaged disease ( p = 0.003; odds ratio: 4.2). The risk of upgraded disease (primary Gleason pattern 4) was significantly decreased 4.5-fold in large prostate glands (>50 ml; p = 0.008). The biochemical recurrence-free survival curves were not significantly different between men who were or were not overweight ( p = 0.950). Conclusions Obese men are at higher risk of upstaged disease, with a proportion of 30% of pT3 disease in RP specimens. BMI should be taken into account for inclusion of low-risk prostate cancer patients in AS programs, and our results may help urologists better inform their obese patients eligible for AS about this risk of reclassification and improve treatment decision making.

Small Prostate Size and High Grade Disease—Biology or Artifact?

Prior radical prostatectomy series have shown an inverse association between prostate size and high grade cancer. It has been suggested that smaller size prostates arise in a low androgen environment, enabling development of more aggressive cancer. We propose that this observation is the result of ascertainment bias driven by prostate specific antigen performance. We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who underwent surgery between 1988 and 2002, and underwent detailed morphometric mapping by a single pathologist. Multivariate linear regression was performed to assess for the effects of age, prostate weight and prostate specific antigen on total and high grade (Gleason grade 4/5) cancer volume and percentage of high grade disease. In patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c), prostate weight was negatively associated (p = 0.0002) with total cancer volume, volume of high grade disease and percentage of high grade disease. For patients who underwent biopsy based on abnormal digital rectal examination (stage T2) these associations were not observed. Improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease. Thus, the association between prostate size and high grade disease may be a consequence of grade dependent performance of prostate specific antigen rather than true tumor biology.

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I125 implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of ≤10 ng/ml; and a Gleason score of ≤6. All patients underwent transrectal ultrasound-guided radioactive I125 seed implantation into the prostate. The prescribed dose was 145 Gy to the prostate planning target volume. A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.

Active Surveillance Program for Prostate Cancer: An Update of the Johns Hopkins Experience

We assessed outcomes of men with prostate cancer enrolled in active surveillance. Since 1995, a total of 769 men diagnosed with prostate cancer have been followed prospectively (median follow-up, 2.7 years; range, 0.01 to 15.0 years) on active surveillance. Enrollment criteria were for very-low-risk cancers, defined by clinical stage (T1c), prostate-specific antigen density < 0.15 ng/mL, and prostate biopsy findings (Gleason score ≤ 6, two or fewer cores with cancer, and ≤ 50% cancer involvement of any core). Curative intervention was recommended on disease reclassification on the basis of biopsy criteria. The primary outcome was survival free of intervention, and secondary outcomes were rates of disease reclassification and exit from the program. Outcomes were compared between men who did and did not meet very-low-risk criteria. The median survival free of intervention was 6.5 years (range, 0.0 to 15.0 years) after diagnosis, and the proportions of men remaining free of intervention after 2, 5, and 10 years of follow-up were 81%, 59%, and 41%, respectively. Overall, 255 men (33.2%) underwent intervention at a median of 2.2 years (range, 0.6 to 10.2 years) after diagnosis; 188 men (73.7%) underwent intervention on the basis of disease reclassification on biopsy. The proportions of men who underwent curative intervention (P = .026) or had biopsy reclassification (P < .001) were significantly lower in men who met enrollment criteria than in those who did not. There were no prostate cancer deaths. For carefully selected men, active surveillance with curative intent appears to be a safe alternative to immediate intervention. Limiting surveillance to very-low-risk patients may reduce the frequency of adverse outcomes.

Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy?

Introduction and ObjectiveBecause of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. Material and methodsA total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a–b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. ResultsFifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a–b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ≥ 7, and 25% were staged pT3. ConclusionAlthough focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated.

A Contemporary Analysis of Outcomes of Adenocarcinoma of the Prostate With Seminal Vesicle Invasion (pT3b) After Radical Prostatectomy

Despite earlier detection and stage migration, seminal vesicle invasion is still reported in the prostate specific antigen era and remains a poor prognostic indicator. We investigated outcomes in men with pT3b disease in the contemporary era. The institutional radical prostatectomy database (1982 to 2010) of 18,505 men was queried and 989 with pT3b tumors were identified. The cohort was split into pre-prostate specific antigen (1982 to 1992), and early (1993 to 2000) and contemporary (2001 to present) prostate specific antigen eras. Of the 732 men identified in the prostate specific antigen era 140 had lymph node involvement and were excluded from study. The Kaplan-Meier method was used to determine biochemical recurrence-free, metastasis-free and prostate cancer specific survival. Proportional hazard models were used to determine predictors of biochemical recurrence-free, metastasis-free and cancer specific survival. In the pre-prostate specific antigen, and early and contemporary prostate specific antigen eras, 7.7%, 4.3% and 3.3% of patients, respectively, had pT3bN0 disease (p >0.001). In pT3bN0 cases, the 10-year biochemical recurrence-free survival rate was 25.8%, 28.6% and 19.6% (p = 0.8), and the cancer specific survival rate was 79.9%, 79.6% and 83.8% (p = 0.6) among the eras, respectively. In pT3bN0 cases in the prostate specific antigen era, prostate specific antigen, clinical stage T2b or greater, pathological Gleason sum 7 and 8-10, and positive surgical margins were significant predictors of biochemical recurrence-free survival on multivariate analysis while clinical stage T2c or greater and Gleason 8-10 were predictors of metastasis-free and cancer specific survival. Despite a decreased frequency of pT3b disease, and lower rates of positive surgical margins and lymph nodes, patients with seminal vesicle invasion continue to have low biochemical recurrence-free survival. Advanced clinical stage, intermediate or high risk Gleason sum at pathological evaluation and positive surgical margins predict biochemical recurrence. High risk clinical stage and Gleason sum predict metastasis-free and cancer specific survival.

981 PCA3 AS A PREDICTOR OF UNFAVORABLE CONFIRMATORY BIOPSY PATHOLOGY IN CANDIDATES FOR ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 2011981 PCA3 AS A PREDICTOR OF UNFAVORABLE CONFIRMATORY BIOPSY PATHOLOGY IN CANDIDATES FOR ACTIVE SURVEILLANCE Sergey Shikanov, Gautam Jayram, Michael S. McGuire, and Charles B. Brendler Sergey ShikanovSergey Shikanov Chicago, IL More articles by this author , Gautam JayramGautam Jayram Chicago, IL More articles by this author , Michael S. McGuireMichael S. McGuire Evanston, IL More articles by this author , and Charles B. BrendlerCharles B. Brendler Evanston, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1013AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary PCA3 is considered a specific marker of prostate cancer volume. We assessed its ability to predict unfavorable confirmatory biopsy pathology in comparison to both PSA and PSA density (PSAD) in men with prostate cancer being considered for active surveillance. METHODS The cohort consisted of 71 candidates for active surveillance with clinical stage T1c, Gleason score 6, positive cores ≤3 and no involvement of a positive core ≥50% on diagnostic biopsy. Confirmatory biopsy revealing Gleason score ≥7, >3 positive cores, or >50% involvement of any single core was considered unfavorable. Urinary PCA3, serum PSA and PSAD were compared among men with favorable and unfavorable confirmatory biopsies. Predictive ability of these parameters was determined by ROC analysis. RESULTS Twenty percent of men (n=14) had unfavorable confirmatory biopsies. Median PCA3 was 30 and 54 (p=0.1) in men with favorable and unfavorable biopsies, respectively. Forty-four percent and 71% had PCA3 >35 among those with favorable and unfavorable biopsies, respectively (p=0.06) (Table 1). On ROC analysis, area under the curve was 0.65 for PCA3 overall, 0.65 for Pca3>35, 0.63 for PSA and 0.72 for PSA density. Table 1. Favorable biopsy, n=57 (80%) Unfavorable biopsy, n=14 (20%) P value PCA3, units 30(32–60) 54(27–95) 0.1⁎ Positive PCA3(>35) 25(44%) 10(71%) 0.06⁎⁎ PSA, ng/ml 3.9(2.6–5.7) 5.1(4.2–5.7) 0.02⁎ PSA density, ng/ml2 0.09(0.05–0.13) 0.18(0.09–0.24) 0.002⁎ ⁎ Rank-sum Wilcoxon test, ⁎⁎ Fisher exact test, continuous data presented as median (0.25–0.75 quartile range), categorical data presented as count (of total) CONCLUSIONS These preliminary results suggest that PCA3 is no better than either PSA or PSAD in predicting the results of confirmatory biopsies in prostate cancer patients being considered for active surveillance. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e395-e396 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sergey Shikanov Chicago, IL More articles by this author Gautam Jayram Chicago, IL More articles by this author Michael S. McGuire Evanston, IL More articles by this author Charles B. Brendler Evanston, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

307 PARTIN TABLES′OVERALL ACCURACY TO PREDICT FINAL PATHOLOGICAL STAGE DETERIORATES IN PATIENTS WITH PROSTATE CANCERS DETECTED BY SATURATION RE-BIOPSY

You have accessJournal of UrologyProstate Cancer: Staging1 Apr 2011307 PARTIN TABLES′OVERALL ACCURACY TO PREDICT FINAL PATHOLOGICAL STAGE DETERIORATES IN PATIENTS WITH PROSTATE CANCERS DETECTED BY SATURATION RE-BIOPSY Herbert Augustin, Marco Auprich, Günter Gallé, Falko Lainer, Badereddin Mohamad Al-Ali, and Karl Pummer Herbert AugustinHerbert Augustin Graz, Austria More articles by this author , Marco AuprichMarco Auprich Graz, Austria More articles by this author , Günter GalléGünter Gallé Graz, Austria More articles by this author , Falko LainerFalko Lainer Graz, Austria More articles by this author , Badereddin Mohamad Al-AliBadereddin Mohamad Al-Ali Graz, Austria More articles by this author , and Karl PummerKarl Pummer Graz, Austria More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.400AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Partin Tables represent a widely used tool to predict pathologic stage in men with localized prostate cancer (PCa). Overall accuracy of the Tables was tested across different populations. However, potential limitations resulting from differences between PCa detected by an initial standard biopsy and saturation re-biopsy has not been analysed so far. METHODS Preoperative serum PSA, clinical stage, and biopsy Gleason sum from 445 patients treated with radical retropubic prostatectomy defined the 2007 Partin probabilities of organ confinement (OC), seminal vesicle invasion (SVI) and extracapsular extension (ECE). PCa was detected by initial biopsy with a maximum of 12 cores in 354 patients (79.5%) and by re-biopsy according a saturation scheme with 24 cores in 91 patients (20.5%). Receiver operating charateristic (ROC) area under the curve (AUC) assessed the predictive accuracy of 2007 Partin Tables relative to observed OC, ECE, and SVI. RESULTS The initial biopsy group presented with clinical stage T1c in 68.4% compared to the saturation group with 75.8% (p=0.369). The mean PSA level was 7.67ng/ml (¡À7.19) in the initial biopsy group, and 10.17ng/ml (¡À7.58) in the saturation group (p=0.004). The initial biopsy group showed Gleason Score ¡(6 in 73.2%, 7 in 20.6% and ¡°Ý8 in 6.2%, the saturation group in 70.3%, 18.7% and 11.0% (p=0.285), respectively. Histopathological evaluation of the prostatectomy specimens revealed stage pT2 in 75.7% of the initial biopsy group vs. 84.6% of the saturation re-biopsy group, pT3a in 16.7% vs. 9.9%, and pT3b in 7.6% vs. 5.5% (p=0.185), respectively. The Partin Tables AUC of the initial and the saturation biopsy group were 0.734 and 0.610 for OC, 0.634 and 0.543 for ECE, and 0.803 and 0.706 for SVI, respectively. CONCLUSIONS The overall accuracy of the 2007 Partin Tables to predict final pathological stage was clearly inferior in patients with prostate cancers detected by re-biopsy according a saturation scheme. Hereby, the accuracies might be undermined by higher mean PSA levels in the presence of similar pathological stages. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e125 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Herbert Augustin Graz, Austria More articles by this author Marco Auprich Graz, Austria More articles by this author Günter Gallé Graz, Austria More articles by this author Falko Lainer Graz, Austria More articles by this author Badereddin Mohamad Al-Ali Graz, Austria More articles by this author Karl Pummer Graz, Austria More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2324 GENETIC RISK ALLELES CAN PREDICT ACTIVE SURVEILLANCE FAILURES

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112324 GENETIC RISK ALLELES CAN PREDICT ACTIVE SURVEILLANCE FAILURES Brian T. Helfand, Barry B. McGuire, Qiaoyan Hu, Daniel C. O'Brien, Cheng Li, Shilajit Kundu, and William J. Catalona Brian T. HelfandBrian T. Helfand Chicago, IL More articles by this author , Barry B. McGuireBarry B. McGuire Chicago, IL More articles by this author , Qiaoyan HuQiaoyan Hu Chicago More articles by this author , Daniel C. O'BrienDaniel C. O'Brien Chicago, IL More articles by this author , Cheng LiCheng Li Chicago, IL More articles by this author , Shilajit KunduShilajit Kundu Chicago, IL More articles by this author , and William J. CatalonaWilliam J. Catalona Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2571AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is debate as to which prostate cancer (CaP) patients require immediate definitive therapy and which may be safely monitored by active surveillance (AS). Because there are no known biomarkers that can predict aggressive disease, ≥60% of men may ultimately fail AS protocols. Recent genome-wide association studies have identified genetic alleles that are associated with CaP susceptibility, and perhaps aggressive pathology. However, their utility in predicting AS failures is unknown. METHODS From March 2003-September 2009, 1376 Caucasian men underwent radical prostatectomy and were genotyped for 17 different risk alleles located on chromosomes 2p15, 3q21m, 5p15, 8q24, 11q13, 17q12, 17q24, 19q13 and Xp11. Candidates for AS were defined by a modified Epstein criteria (JAMA. 1994. 271: 368): clinical stage T1c, PSA<10ng/ml, Gleason grade ≤6, tumor involving ≤3 cores and no more than 50% of any single core. ″Failures″ and ″successes″ of AS were defined by the presence or absence of pathologic Gleason grade ≥7 and/or pathologic stage ≥T3. Comparisons were made between the frequency of risk alleles in ″failures″ and ″successes.″ RESULTS 181 (13.2%) men initially met criteria for AS. Of this population, there were 33 (18.2%) ″failures″ and 148 (81.8%) ″successes.″ 7 of the 17 CaP risk alleles were over-represented in ″failures″ compared to ″successes.″ Specifically, there was a significantly higher frequency of the 8q24 risk alleles SNP rs1447295 and SNP rs16902094 in failures compared to successes (Table 1). Allele Frequencies for Active Surveillance Failures vs. Successes. CaP Risk Allele Chromosome Allele Freuency ‘AS Failures’ Allele Frequency ‘AS Successes’ p value rs1447295 8q24 30.8% 14.8% 0.04 rs16902094 8q24 29.4% 13.8% 0.02 CONCLUSIONS Prior studies have suggested that risk loci on 8q24 confer disease aggressiveness (e.g. Eur J Hum Genet. 2008.16: 496). This study suggests that these 8q24 alleles may have utility in selecting appropriate candidates for AS. Future prospective studies are required to further establish the true utility of the CaP risk alleles. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e932 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian T. Helfand Chicago, IL More articles by this author Barry B. McGuire Chicago, IL More articles by this author Qiaoyan Hu Chicago More articles by this author Daniel C. O'Brien Chicago, IL More articles by this author Cheng Li Chicago, IL More articles by this author Shilajit Kundu Chicago, IL More articles by this author William J. Catalona Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2322 PCA3 VARIABILITY IN MEN WITH VERY LOW RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112322 PCA3 VARIABILITY IN MEN WITH VERY LOW RISK PROSTATE CANCER Sergey Shikanov, Gautam Jayram, Michael S. McGuire, and Charles B. Brendler Sergey ShikanovSergey Shikanov Chicago, IL More articles by this author , Gautam JayramGautam Jayram Chicago, IL More articles by this author , Michael S. McGuireMichael S. McGuire Evanston, IL More articles by this author , and Charles B. BrendlerCharles B. Brendler Evanston, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2569AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary PCA3 is considered a specific marker of prostate cancer tumor volume. We hypothesized that it will remain stable in patients with minimal disease without treatment. METHODS 41 men with very low risk prostate cancer were enrolled in an IRB-approved active surveillance protocol. All men had clinical stage T1c, Gleason score 6, positive cores ≤3 and involvement of no positive core ≥50%. Urinary PCA3 was measured at enrollment and at 6 months. We assessed percent change ([enrollment PCA3–6 months PCA3 /enrollment PCA3]x100%) and proportion of positive tests (PCA3 score >35) at both time points. None of the patients had evidence of clinical progression during the observation period. RESULTS Table 1 summarizes the cohort parameters. Median %PCA3 change was only 3%, and 46% of patients had positive PCA3 score both at enrollment and 6 months. However, compared to the enrollment PCA3 score, at 6 months the PCA3 score varied by more than 25% in 58% (n=24) and by more than 50% in 31% (n=13) of patients(Figure 1). When comparing PSA changes in the same population, PSA varied by more than 25% in only 41% (n=17) and by more than 50% in 7% (n=3) of patients. Table 1. Cohort parameters, n=41 Positive cores 1 22(54%) 2 15(36%) 3 4(10%) Max.% of core involvement 5(4–10) Enrollment PCA3 31(19–69) 6 month PCA3 34(16–59) % change PCA3 3(−31–35) Enrollment PCA3 > 35 19(46%) 6 moths PCA3 > 35 19(46%) Enrollment PSA, ng/ml 4.2(3.0–5.3) 6 months PSA, ng/ml 3.3(2.9–5.5) % change PSA 1(−18–25) Continuous data presented as median (0.25–0.75 quartile range), categorical data presented as count (of total). CONCLUSIONS While urinary PCA3 scores on average change only slightly over 6 months in clinically stable men with very low risk prostate cancer, PCA3 scores vary significantly among individual patients. Given this variability, the usefulness of PCA3 in guiding treatment recommendations for the individual patient remains uncertain. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e931 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sergey Shikanov Chicago, IL More articles by this author Gautam Jayram Chicago, IL More articles by this author Michael S. McGuire Evanston, IL More articles by this author Charles B. Brendler Evanston, IL More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

1095 VALUE OF EARLY CONFIRMATORY BIOPSIES AND CENTRALIZED PATHOLOGICAL REVIEW TO SELECT PROSTATE CANCER PATIENTS FOR ACTIVE SURVEILLANCE

1095 VALUE OF EARLY CONFIRMATORY BIOPSIES AND CENTRALIZED PATHOLOGICAL REVIEW TO SELECT PROSTATE CANCER PATIENTS FOR ACTIVE SURVEILLANCE

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Learning curve for radical retropubic prostatectomy

The learning curve is a period in which the surgical procedure is performed with difficulty and slowness, leading to a higher risk of complications and reduced effectiveness due the surgeon's inexperience. We sought to analyze the residents' learning curve for open radical prostatectomy (RP) in a training program. We conducted a prospective study from June 2006 to January 2008 in the academic environment of the University of Sao Paulo. Five residents operated on 184 patients during a four-month rotation in the urologic oncology division, mentored by the same physician assistants. We performed sequential analyses according to the number of surgeries, as follows: ≤ 10, 11 to 19, 20 to 28, and ≥ 29. The residents performed an average of 37 RP each. The average psa was 9.3 ng/mL and clinical stage T1c in 71% of the patients. The pathological stage was pT2 (73%), pT3 (23%), pT4 (4%), and 46% of the patients had a Gleason score 7 or higher. In all surgeries, the average operative time and estimated blood loss was 140 minutes and 488 mL. Overall, 7.2% of patients required blood transfusion, and 23% had positive surgical margins. During the initial RP learning curve, we found a significant reduction in the operative time; blood transfusion during the procedures and positive surgical margin rate were stable in our series.

Clinically low-risk prostate cancer: evaluation with transrectal doppler ultrasound and functional magnetic resonance imaging

OBJECTIVES:To evaluate transrectal ultrasound, amplitude Doppler ultrasound, conventional T2‐weighted magnetic resonance imaging, spectroscopy and dynamic contrast‐enhanced magnetic resonance imaging in localizing and locally staging low‐risk prostate cancer.INTRODUCTION:Prostate cancer has been diagnosed at earlier stages and the most accepted classification for low‐risk prostate cancer is based on clinical stage T1c or T2a, Gleason score ≤6, and prostate‐specific antigen (PSA) ≤10 ng/ml.METHODS:From 2005 to 2006, magnetic resonance imaging was performed in 42 patients, and transrectal ultrasound in 26 of these patients. Seven patients were excluded from the study. Mean patient age was 64.94 years and mean serum PSA was 6.05 ng/ml. The examinations were analyzed for tumor identification and location in prostate sextants, detection of extracapsular extension, and seminal vesicle invasion, using surgical pathology findings as the gold standard.RESULTS:Sixteen patients (45.7%) had pathologically proven organ‐confined disease, 11 (31.4%) had positive surgical margin, 8 (28.9%) had extracapsular extension, and 3 (8.6%) presented with extracapsular extension and seminal vesicle invasion.Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy values for localizing low‐risk prostate cancer were 53.1%, 48.3%, 63.4%, 37.8% and 51.3% for transrectal ultrasound; 70.4%, 36.2%, 65.1%, 42.0% and 57.7% for amplitude Doppler ultrasound; 71.5%, 58.9%, 76.6%, 52.4% and 67.1% for magnetic resonance imaging; 70.4%, 58.7%, 78.4%, 48.2% and 66.7% for magnetic resonance spectroscopy; 67.2%, 65.7%, 79.3%, 50.6% and 66.7% for dynamic contrast‐enhanced magnetic resonance imaging, respectively.Sensitivity, specificity, PPV, NPV and accuracy values for detecting extracapsular extension were 33.3%, 92%, 14.3%, 97.2% and 89.7% for transrectal ultrasound and 50.0%, 77.6%, 13.7%, 95.6% and 75.7% for magnetic resonance imaging, respectively. For detecting seminal vesicle invasion, these values were 66.7%, 85.7%, 22.2%, 97.7% and 84.6% for transrectal ultrasound and 40.0%, 83.1%, 15.4%, 94.7% and 80.0% for magnetic resonance imaging.CONCLUSION:Although preliminary, our results suggest that imaging modalities have limited usefulness in localizing and locally staging clinically low‐risk prostate cancer.

Prostate Cancer Antigen 3 Score Accurately Predicts Tumour Volume and Might Help in Selecting Prostate Cancer Patients for Active Surveillance

BackgroundThe optimal selection of prostate cancer (PCa) patients for active surveillance (AS) is currently being debated. ObjectiveTo assess the impact of urinary prostate cancer antigen 3 (PCA3) score as an AS criterion instead of and in addition to the current criteria. Design, setting, and participantsWe prospectively studied 106 consecutive low-risk PCa patients (prostate-specific antigen [PSA] ≤10ng/ml, clinical stage T1c–T2a, and biopsy Gleason score 6) who underwent a PCA3 urine test before radical prostatectomy (RP). MeasurementsPerformance of AS criteria (biopsy criteria, PCA3 score, PSA density, and magnetic resonance imaging [MRI] findings) was tested in predicting four prognostic pathologic findings in RP specimens: (1) pT3–4 disease; (2) overall unfavourable disease (OUD) defined by pT3–4 disease and/or pathologic primary Gleason pattern 4; (3) tumour volume <0.5cm3; and (4) insignificant PCa. Results and limitationsThe PCA3 score was strongly correlated with the tumour volume in a linear regression analysis (p<0.001, r=0.409). The risk of having a cancer ≥0.5cm3 and a significant PCa was increased three-fold in men with a PCA3 score of ≥25 compared with men with a PCA3 score of <25 with most AS biopsy criteria used. There was a trend towards higher PCA3 scores in patients with unfavourable and non–organ-confined disease and Gleason >6 cancers. In a multivariate analysis taking into account each AS criterion, a high PCA3 score (≥25) was an important predictive factor for tumour volume ≥0.5cm3 (odds ratio [OR]: 5.4; p=0.010) and significant PCa (OR: 12.7; p=0.003). Biopsy criteria and MRI findings were significantly associated with OUD (OR: 3.9 and 5.0, respectively; p=0.030 and p=0.025, respectively). ConclusionsPCA3 score may be a useful marker to improve the selection for AS in addition to the current AS criteria. With a predictive cut-off of 25, PCA3 score is strongly indicative for tumour volume and insignificant PCa.