68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography-Based Primary Staging and Histological Correlation after Extended Pelvic Lymph Node Dissection in Intermediate-Risk Prostate Cancer.

OBJECTIVE: The objective of this study is to evaluate prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT)-based primary staging in exclusively D'Amico intermediate-risk prostate cancer (PCa) patients. PATIENTS AND METHODS: We relied on the Braunschweig institutional database and retrospectively identified D'Amico intermediate-risk PCa patients who were administered to 68Ga-PSMA PET/CT-based primary staging prior to consecutive radical prostatectomy and extended lymph node dissection. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 39), per-pelvic side (n = 78), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 203), respectively. RESULTS: Sensitivity, specificity, PPV, and NPV per-patient were 20.0, 94.1, 33.3, and 88.9%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were 16.7, 97.2, 33.3, and 93.3%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were 16.7, 99.0, 33.3, and 97.5%, respectively. CONCLUSIONS: We recorded high rates of specificity and NPV for 68Ga-PSMA PET/CT-based primary staging in D'Amico intermediate-risk PCa patients. Conversely, the sensitivity and PPV were lower than anticipated. Larger and favorably prospective trials are needed to verify our results and to unravel possible bias from such smaller studies.

Stone Localization Is Pivotal for the Success of Percutaneous Nephrolithotomy.

OBJECTIVE: The objective of this study was to predict computed tomography (CT)-controlled treatment success after minimally invasive percutaneous nephrolithotomy (Mini-PCNL). PATIENTS AND METHODS: We relied on retrospective single institutional data from 92 kidney stone patients treated with Mini-PCNL. Residual stones after treatment were evaluated by post-Mini-PCNL CT scans. Stone-free status was defined as clinically insignificant residual stones ≤3 mm after surgery. Multivariable logistic regression analyses predicted stone-free status after Mini-PCNL. RESULTS: Overall, 53 (57.6%) patients achieved stone-free status after Mini-PCNL treatment. In multivariable logistic regression analyses, stone localization was the strongest predictor for stone-free status after Mini-PCNL. Specifically, patients with exclusively pelvic stones were 7.1-fold more likely to achieve stone-free status than those patients with stones at multiple localizations (OR: 7.1; p = 0.005). Additionally, stone size represented a barrier for stone-free status (OR: 0.9; p = 0.03). CONCLUSIONS: Stone localization revealed the highest impact on treatment success after Mini-PCNL. Especially, those patients with exclusively pelvic stones were most likely to achieve stone-free status. Conversely, patients with multiple stone localizations were less likely to achieve stone-free status and need to be informed about higher risk of additional interventions after initial Mini-PCNL.

68Ga-PSMA PET/CT based primary staging and histological correlation after extended pelvic lymph node dissection at radical prostatectomy.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT) represents the upcoming standard for the staging of prostate cancer (PCa). However, there is still an unmet need for the validation of PSMA PET/CT at primary staging and consecutive histological correlation. Consequently, we decided to analyze the prediction parameter of PSMA PET/CT at primary staging. METHODS: We relied on 90 ≥ intermediate-risk PCa patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection. All patients were administered to 68Ga-PSMA PET/CT prior to surgery. 68Ga-PSMA PET/CT data were retrospectively reevaluated by a single radiologist and consequently compared to histological results from RP. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 90), per-pelvic side (n = 180), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 458), respectively. RESULTS: Sensitivity, specificity, PPV, and NPV per-patient were: 43.8, 96.0, 70.0, and 88.8%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were: 42.9, 95.6, 56.3, and 92.7%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were: 47.6, 98.9, 66.7, and 97.5%, respectively. CONCLUSIONS: Negative 68Ga-PSMA PET/CT results were highly reliable in our study. Positive 68Ga-PSMA PET/CT results, however, revealed less reliable results. Larger and ideally prospective trials are justified to clarify the potential role of PSMA PET/CT based primary staging.

Elastography Targeted Prostate Biopsy in Patients under Active Surveillance.

OBJECTIVE: The aim of this study was to examine elastography-based prostate biopsy in prostate cancer (PCa) patients under active surveillance. PATIENTS AND METHODS: We relied on PCa patients who opted for active surveillance and underwent elastography targeted and systematic follow-up biopsy at the Braunschweig Prostate Cancer Center between October 2009 and February 2015. Each prostate sextant was considered as an individual case. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) for elastography to predict follow-up biopsy results were analyzed, respectively, and 95 % confidence intervals (CIs) were carried out by using 2000 bootstrapping sample analyses. RESULTS: Overall, 50 men and 300 sextants were identified. Overall, 27 (54%) men and 66 (22%) sextants harbored PCa at follow-up biopsy. Sensitivity, specificity, PPV, NPV, and ACC for elastography to predict follow-up biopsy results were: 19.7 (95% CI: 11.9-27.3), 86.8 (95% CI: 82.7-90.3), 29.6 (95% CI: 14.6-46.0), 79.3 (95% CI: 71.6-86.5), and 72.0% (95% CI: 65.7-78.3), respectively. CONCLUSIONS: We recorded limited reliability of elastography-based prediction of follow-up biopsy results in active surveillance patients. Based on our analyses, we can neither recommend to rely exclusively on elastography-based targeted biopsies nor to delay or to omit follow-up biopsies based on elastography results during active surveillance.

Only Size Matters in Stone Patients: Computed Tomography Controlled Stone-Free Rates after Mini-Percutaneous Nephrolithotomy.

OBJECTIVE: To examine and predicting stone-free rates (SFRs) after minimally invasive-percutaneous nephrolithotomy (mini-PNL) based on computed tomography (CT), instead of X-ray or ultrasound control. PATIENTS AND METHODS: We identified 146 mini-PNL patients with pre- and postoperative CT scans. Patient and stone characteristics were assessed. Stone-free status was defined as ≤3 mm residual fragment after mini-PNL according to postsurgery CT scan. Multivariable logistic regression analyses predicted stone-free status after mini-PNL. RESULTS: Overall, 62 (42.5%) patients achieved stone-free status after mini-PNL. In multivariable analyses, stone size was the only independent predictor for stone-free status (OR 0.9; p = 0.02). Patients with stones > 20 mm were less likely to achieve stone-free status, than those harboring stones 10-20 mm (OR 0.3; p = 0.009). SFRs according to stone size categories (< 10, 10-20, and > 20 mm) were 33.3, 50.5, and 25%. Body mass index (BMI) and stone density (Houndsfield units) were no independent predictors for stone-free status after mini-PNL. CONCLUSIONS: We report lower SFRs than expected. Stone size was the only independent predictor for stone-free status after mini-PNL. Patients with larger stones need to be informed about high risk of additional interventions. High BMI and high stone density do not represent a barrier for stone-free status after mini-PNL.

Obesity paradox in prostate cancer: increased body mass index was associated with decreased risk of metastases after surgery in 13,667 patients.

INTRODUCTION: Obesity might negatively affect prostate cancer (PCa) outcomes. However, evidence according to the associations between obesity and metastases-free survival after radical prostatectomy (RP) is still inconsistent. METHODS: We relied on PCa patients treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable Cox regression analyses examined the impact of obesity on metastases after RP. Last, in a propensity score matched cohort, Kaplan-Meier analyses assessed metastases-free survival according to body mass index (kg/m2) (BMI) strata (≥ 30 vs. < 25). RESULTS: Of 13,667 individuals, 1990 (14.6%) men were obese (BMI ≥ 30). Median follow-up was 36.4 month (IQR 13.3-60.8). Obese patients were less likely to exhibit metastases after RP (HR 0.7, 95% CI 0.5-0.97, p = 0.03). Similarly, after propensity score adjustment, obesity was associated with increased metastases-free survival (log rank p = 0.001). CONCLUSION: We recorded the obesity paradox phenomenon in PCa patients. In particular, high BMI (≥ 30) was associated with decreased risk of metastases after RP, despite an increased risk being anticipated. Whether statin use might have affected the results was not assessed. Further research is needed to unravel the controversially debated association between obesity and PCa.

Population-Based External Validation of the Updated 2012 Partin Tables in Contemporary North American Prostate Cancer Patients.

OBJECTIVE: To externally validate the updated 2012 Partin Tables in contemporary North American patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa) at community institutions. MATERIALS AND METHODS: We examined records of 25,254 patients treated with RP and pelvic lymph node dissection (PLND) between 2010 and 2013, within the surveillance, epidemiology, and end results database. The ROC derived AUC assessed discriminant properties of the updated 2012 Partin Tables of organ confined disease (OC), extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI). Calibration plots focused on calibration between predicted and observed rates. RESULTS: Proportions of OC, ECE, SVI, and LNI at RP were 69.8%, 18.4%, 7.4%, and 4.4%, respectively. Accuracy for prediction of OC, ECE, SVI, and LNI was 70.4%, 59.9%, 72.9%, and 77.1%, respectively. In subgroup analyses in patients with nodal yield >10, accuracy for LNI prediction was 76.0%. Subgroup analyses in elderly patients and in African American patients revealed decreased accuracy for prediction of all four endpoints. Last but not least, SVI and LNI calibration plots showed excellent agreement, versus good agreement for OC (maximum underestimation of 10%) and poor agreement for ECE (maximum overestimation of 12%). CONCLUSION: Taken together, the updated 2012 Partin Tables can be unequivocally endorsed for prediction of OC, SVI, and LNI in community-based patients with localized PCa. Conversely, ECE predictions failed to reach the minimum accuracy requirements of 70%. Prostate 77:105-113, 2017. © 2016 Wiley Periodicals, Inc.

Population-Based Validation of the 2014 ISUP Gleason Grade Groups in Patients Treated With Radical Prostatectomy, Brachytherapy, External Beam Radiation, or no Local Treatment.

BACKGROUND: To test discriminant ability of the 2014 ISUP Gleason grade groups (GGG) for prediction of prostate cancer specific mortality (PCSM) after radical prostatectomy (RP), brachytherapy (BT), external beam radiation (EBRT) or no local treatment (NLT) relative to traditional Gleason grading (TGG). METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-database (2004-2009), 2,42,531 non-metastatic prostate cancer (PCa) patients were identified, who underwent local treatment (RP, BT, EBRT only) or NLT. Follow-up endpoint was PCSM. Biopsy and/or pathological Gleason score (GS) were categorized as TGG ≤6, 7, 8-10 or GGG: I (≤6), II (3 + 4), III (4 + 3), IV (8), and V (9-10). Kaplan-Meier plots, multivariable Cox regression analyses and receiver operating characteristics (ROC) area under the curve analyses (AUC) were used. RESULTS: Median follow-up was 76 months (IQR: 59-94). For the four examined treatment modalities, all five GGG strata and all three TGG strata independently predicted PCSM. GGG yielded 1.5-fold or greater HR differences between GGG II and GGG III, and twofold or greater HR differences between GGG IV and GGG V. Relative to TGG, GGG added 0.4-1.1% to AUC. CONCLUSIONS: This large population-based cohort study confirms the added discriminant properties of the novel GGG strata and confirms a modest gain in predictive accuracy. Prostate 77: 686-693, 2017. © 2017 Wiley Periodicals, Inc.

North American Population-Based Validation of the National Comprehensive Cancer Network Practice Guideline Recommendation of Pelvic Lymphadenectomy in Contemporary Prostate Cancer.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend a pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) if a nomogram predicted risk of lymph node invasion (LNI) is ≥2%. We examined this and other thresholds, including nomogram validation. METHODS: We examined records of 26,713 patients treated with RP and PLND between 2010 and 2013, within the Surveillance, Epidemiology, and End Results database. Nomogram thresholds of 2-5% were tested and external validation was performed. RESULTS: LNI was recorded in 4.7% of patients. Nomogram accuracy was 80.4% and maintained minimum accuracy of 75.6% in subgroup analyses, according to age, race, and nodal yield >10. With the NCCN recommended 2% nomogram threshold, PLND could be avoided in 22.3% of patients at the expense of missing 3.0% of individuals with LNI. Alternative thresholds of 3%, 4%, and 5% yielded respective PLND avoidance rates of 60.4%, 71.0%, and 79.8% at the expense of missing 17.8%, 27.2%, and 36.6% of patients with LNI. NCCN cut-off recommendation was best satisfied with a threshold of <2.6%, at which PLND could be avoided in 13,234 patients (49.5%) versus missing 141 patients with LNI (11.2%). CONCLUSION: NCCN LNI nomogram remains accurate in contemporary patients. However, the 2% threshold appears to be too strict, since only 22.3% of PLNDs can be avoided, instead of the stipulated 47.7%. The optimal 2.6% threshold allows a higher rate of PLND avoidance (49.5%), at the cost of 11.2% missed instances of LNI, as recommended by NCCN guidelines. PATIENT SUMMARY. External validation in contemporary SEER prostate cancer patients showed that the NCCN nomogram remains accurate for predicting lymph node invasion and seems to be optimal at an alternative 2.6% threshold, with best ratio of avoided pelvic lymph node dissections (49.5%) and missed LNIs (11.2%), as recommended by NCCN guideline. Prostate 77:542-548, 2017. © 2017 Wiley Periodicals, Inc.

Defining biochemical recurrence after radical prostatectomy and timing of early salvage radiotherapy : Informing the debate.

BACKGROUND: The optimal prostate-specific antigen (PSA) level after radical prostatectomy (RP) for defining biochemical recurrence and initiating salvage radiation therapy (SRT) is still debatable. Whereas adjuvant or extremely early SRT irrespective of PSA progression might be overtreatment for some patients, SRT at PSA >0.2 ng/ml might be undertreatment for others. The current study addresses the optimal timing of radiation therapy after RP. PATIENTS AND METHODS: Cohort 1 comprised 293 men with PSA 0.1-0.19 ng/ml after RP. Cohort 2 comprised 198 men with SRT. PSA progression and metastases were assessed in cohort 1. In cohort 2, we compared freedom from progression according to pre-SRT PSA (0.03-0.19 vs. 0.2-0.499 ng/ml). Multivariable Cox regression analyses predicted progression after SRT. RESULTS: In cohort 1, 281 (95.9%) men had further PSA progression ≥0.2 ng/ml and 27 (9.2%) men developed metastases within a median follow-up of 74.3 months. In cohort 2, we recorded improved freedom from progression according to lower pre-SRT PSA (0.03-0.19 vs. 0.2-0.499 ng/ml: 69 vs. 53%; log-rank p = 0.051). Patients with higher pre-SRT PSA ≥0.2 ng/ml were at a higher risk of progression after SRT (hazard ratio: 1.8; p < 0.05). CONCLUSION: The vast majority of patients with PSA ≥0.1 ng/ml after RP will progress to PSA ≥0.2 ng/ml. Additionally, early administration of SRT at post-RP PSA level <0.2 ng/ml might improve freedom from progression. Consequently, we suggest a PSA threshold of 0.1 ng/ml to define biochemical recurrence after RP.

Primary Gleason pattern upgrading in contemporary patients with D'Amico low-risk prostate cancer: implications for future biomarkers and imaging modalities.

OBJECTIVE: To retrospectively assess the rate of high-grade primary Gleason upgrading (HGPGU) to primary Gleason pattern 4 or 5 in a contemporary cohort of patients with D'Amico low-risk prostate cancer including those who fulfilled Prostate Cancer Research International Active Surveillance (PRIAS) criteria, and to develop a tool for HGPGU prediction. HGPGU is a contraindication in most active surveillance (AS) and focal therapy protocols. PATIENTS AND METHODS: In all, 10 616 patients with localised prostate cancer were treated at a high-volume European tertiary care centre from 2010 to 2015 with radical prostatectomy. Analyses were restricted to 1 819 patients with D'Amico low-risk prostate cancer (17.1%) with prostate-specific antigen (PSA) levels of <10.0 ng/mL, cT1c-cT2a and Gleason score ≤6, and were repeated within 772 of the men (7.3%) who fulfilled the PRIAS criteria for AS (PSA level of ≤10 ng/mL, T1c-T2, Gleason score ≤6, PSA density (PSAD) of <0.2 ng/mL2 , ≤2 positive cores). Uni- and multivariable logistic regression models were fitted, testing predictors of HGPGU. The final logistic regression model was based on the most informative variables. RESULTS: There was HGPGU in 88 (4.8%) patients with D'Amico low-risk prostate cancer and in 32 (4.1%) of the subgroup who were PRIAS eligible. Multivariable analysis predicting HGPGU for the patients with D'Amico low-risk yielded three independent predictors: age, PSAD, and clinical tumour stage (P = 0.008, P = 0.005 and P = 0.021, respectively). Within the same patients, the model using all vs the most informative variables resulted in area under the curves (AUCs) of 69.2% and 68.3%, respectively. Multivariable analysis of those who were PRIAS eligible, yielded age and number of positive cores as independent predictors of HGPGU (P = 0.002 and P = 0.049, respectively; AUC 64.9%). CONCLUSIONS: The low accuracy (invariably <70%) for HGPGU prediction in both patients with D'Amico low-risk prostate cancer and PRIAS eligibility indicates that these variables have poor predictive ability in contemporary patients. Despite HGPGU being a rare phenomenon, it may have life threatening implications and consequently alternatives such as biomarkers, genetic markers, or imaging modalities at re-biopsy are needed.

External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer.

BACKGROUND: Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported. AIM: To examine testosterone kinetics in a large series of contemporary patients after EBRT. METHODS: The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses. OUTCOMES: Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence. RESULTS: Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone < 8 nmol/L). Of all patients with testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence. CLINICAL IMPLICATIONS: EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism. STRENGTHS AND LIMITATIONS: We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study lacked information on health-related quality-of-life data. CONCLUSION: Our findings indicate that up to 75% of patients will have a profound testosterone decrease, with up to a 40% increase in rates of biochemical hypogonadism, although the latter events will leave biochemical recurrence unaffected. Pompe RS, Karakrewicz PI, Zaffuto E, et al. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer. J Sex Med 2017;14:876-882.

A proposal of a new nomogram for predicting upstaging in contemporary D'Amico low-risk prostate cancer patients.

PURPOSE: Unfavorable prostate cancer (PCa) disease at final pathology affects at least 10 % of D'Amico low-risk patients. Thus, conservative therapies including active surveillance may be wrongfully applied. The purposes were to assess the rate of upstaging in a contemporary cohort of D'Amico low-risk PCa patients and to develop and externally validate a nomogram as upstaging prediction tool in two European cohorts. METHODS: Analyses were restricted to 2007 patients who harbored low-risk PCa at ≥10-cores initial biopsy according to D'Amico classification (PSA <10.0 ng/ml, Gleason score <7 and clinical stage ≤T2a). Patients underwent radical prostatectomy at a high-volume center in Hamburg, Germany, from 2010 to 2015. The Hamburg cohort was randomly divided into development (n = 1338) and validation cohorts (n = 669). The development cohort was used to devise a nomogram predicting upstaging, defined as presence of ≥pT3 and/or lymph node invasion. The nomogram was externally validated in two European validation cohorts (Hamburg, n = 669; Milan, n = 465). RESULTS: Upstaging was observed in 187/1338 (14.0 %) of low-risk patients. In multivariable models, four of ten tested variables achieved independent predictor status: age (OR 1.07, 95 % CI 1.04-1.09), PSA (OR 1.21, 95 % CI 1.12-1.31), prostate volume (OR 0.97, 95 % CI 0.96-0.98) and percentage of positive cores (OR 1.02, 95 % CI 1.01-1.03). In external validation, the nomogram demonstrated 70.8 % (Hamburg) and 70.0 % (Milan) accuracy, respectively, with excellent concordance between predicted and observed values. CONCLUSIONS: Our proposed nomogram is capable to accurately identify D'Amico low-risk patients at risk of upstaging, utilizing four routinely available clinical variables, age, PSA, prostate volume and percentage of positive biopsy cores. Unfavorable prostate cancer disease at final pathology affects at least 10 % of D'Amico low-risk patients. Thus, we developed and externally validated a new nomogram based on contemporary low-risk prostate cancer patients to accurately identify D'Amico low-risk patients at risk of upstaging. It utilizes four routine variables, age, PSA, prostate volume and percentage of positive biopsy cores.

Differences in Patient Characteristics among Men Choosing Open or Robot-Assisted Radical Prostatectomy in Contemporary Practice - Analysis of Surveillance, Epidemiology, and End Results Database.

OBJECTIVE: To examine characteristics of robot-assisted (RARP) and open radical prostatectomy (ORP) patients. PATIENTS AND METHODS: We relied on the Surveillance, Epidemiology, and End Results-Medicare-linked database and focused on prostate cancer patients between 2008 and 2009. In multivariable logistic regression analyses, we predicted RARP. RESULTS: Of 5,915 patients, 3,476 (58.8%) underwent RARP and 2,439 (41.2%) ORP. Patients within intermediate (OR 1.4, p = 0.01) or highest (OR 1.5, p = 0.02) education strata and those treated by surgeons with a high volume (OR 2.2, p < 0.001) were more likely to undergo RARP. Conversely, those residing in rural areas (OR 0.7, p = 0.005) and those with clinical stage T2 or higher (OR 0.7, p = 0.006) were less likely to undergo RARP. Additionally, patients from the Southwest were less likely to undergo RARP (OR 0.4, p < 0.001), but those from the Northern Plains were more likely to undergo RARP (OR 1.4, p = 0.02) than their counterparts from the East. Finally, RARP patients were neither younger nor healthier than ORP patients. CONCLUSIONS: Several patient characteristics such as education, region of residence and population density affect the likelihood of RARP vs. ORP treatment. Similarly, clinical stage and surgeon characteristics also affect the assignment to one or other treatment modality.

Low Other Cause Mortality Rates Reflect Good Patient Selection in Patients with Prostate Cancer Treated with Radical Prostatectomy.

PURPOSE: Treatment decisions in patients with prostate cancer are affected by patient age regardless of higher life expectancy compared to the baseline population. Our aim was to quantify cancer specific and other cause mortality rates after radical prostatectomy. MATERIALS AND METHODS: A total of 8,741 patients with prostate cancer underwent radical prostatectomy between 1992 and 2009 at a European center. Ten-year other cause and cancer specific mortality rates were determined by age and comorbidities, and age and Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) risk groups. Competing risk regression was used for risk factor analyses including clinical and pathological variables. RESULTS: Ten-year other cause mortality rates increased with patient age, including 4.8%, 9.8%, 13.6% and 16.5% in men younger than 60, 60 to 64, 65 to 69 and 70 years or older, respectively. Cancer specific mortality was the leading cause of death in CAPRA-S high risk cases regardless of age. On multivariate analyses age groups achieved independent predictor status for other cause mortality (ages 60 to 64 years HR 1.81, 95% CI 1.26-2.62, 65 to 69 years HR 2.48, 95% CI 1.73-3.56 and 70 years or greater HR 3.02, 95% CI 1.97-4.62) as well as Charlson comorbidity indexes 1 (HR 1.45, 95% CI 1.00-2.09) and 3 or greater (HR 3.99, 95% CI 1.57-10.1). Gleason score 3 + 4 and 4 + 3 or greater, pT3b stage, lymph node invasion and positive margin status achieved independent predictor status when the end point was cancer specific mortality. The CAPRA-S high risk constellation increased cancer specific mortality risk in multifold fashion (HR 26, 95% CI 16-56). CONCLUSIONS: In patients with the CAPRA-S high risk constellation the rate of cancer specific mortality increased in multifold fashion and contributed to most deaths regardless of patient age. Low other cause mortality rates in all age groups showed reasonable patient selection.

Limitations of Elastography Based Prostate Biopsy.

PURPOSE: The role of elastography in patients initially and at repeat prostate biopsy is still indeterminate. The existing literature is sparse and controversial. MATERIALS AND METHODS: We studied patients who underwent elastography based and systematic biopsy between October 2009 and February 2015 at Braunschweig Prostate Cancer Center. Patients were separated according to first vs repeat biopsy setting. Each prostate sextant was considered an individual case. The sensitivity, specificity, positive and negative predictive values, and accuracy of elastography to predict biopsy results were analyzed. The 95% CIs were determined by bootstrapping analysis of 2,000 samples. RESULTS: Overall 679 men and a total of 4,074 sextants were identified. Of the 679 men 160 (23.6%) underwent first biopsy and 519 (76.4%) underwent repeat biopsy. In the 160 men at first biopsy sensitivity was 18.0% (95% CI 14.5-21.3), specificity was 87.7% (95% CI 85.3-89.9), positive predictive value was 36.6% (95% CI 28.4-45.4), negative predictive value was 73.0% (95% CI 67.5-77.9) and accuracy was 67.9% (95% CI 63.4-72.2). Results in 519 men (76.4%) at repeat biopsy were 19.8% (95% CI 16.0-23.7), 90.9% (95% CI 89.9-91.9), 20.1% (95% CI 15.8-24.8), 90.7% (95% CI 89.0-92.3) and 83.5% (95% CI 81.6-85.2), respectively. CONCLUSIONS: We found limited reliability of elastography prediction at prostate biopsy in patients at first and repeat biopsies. Based on our analyses we cannot recommend a variation of well established systematic biopsy patterns or a decrease in biopsy cores based on elastography.

Salvage radical prostatectomy for recurrent prostate cancer: verification of European Association of Urology guideline criteria.

OBJECTIVE: To analyse oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer and to compare outcomes of patients within and outside the European Association of Urology (EAU) guideline criteria (organ-confined prostate cancer ≤T2b, Gleason score ≤7 and preoperative PSA level <10 ng/mL) for SRP. PATIENTS AND METHODS: In all, 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analysed. Kaplan-Meier curves assessed time to biochemical recurrence (BCR), metastasis-free survival (MFS) and cancer-specific survival. Cox regressions addressed factors influencing BCR and MFS. BCR was defined as a PSA level of >0.2 ng/mL and rising, continence as the use of 0-1 safety pad/day, and potency as a five-item version of the International Index of Erectile Function score of ≥18. RESULTS: The median follow-up was 36 months. After SRP, 42.0% of the patients experienced BCR, 15.9% developed metastasis, and 5.5% died from prostate cancer. Patients fulfilling the EAU guideline criteria were less likely to have positive lymph nodes (LNs) and had significantly better BCR-free survival (5-year BCR-free survival 73.9% vs 11.6%; P = 0.001). In multivariate analysis, low-dose-rate brachytherapy as primary treatment (P = 0.03) and presence of positive LNs at SRP (P = 0.02) were significantly associated with worse BCR-free survival. The presence of positive LNs or Gleason score >7 at SRP were independently associated with metastasis. The urinary continence rate at 1 year after SRP was 74%. Seven patients (12.7%) had complications ≥III (Clavien grade). CONCLUSION: SRP is a safe procedure providing good cancer control and reasonable urinary continence. Oncological outcomes are significantly better in patients who met the EAU guideline recommendations.

True targeting-derived prostate biopsy: HistoScanning™ remained inadequate despite advanced technical efforts.

PURPOSE: To verify the reliability of HistoScanning™-based, true targeting (TT)-derived prostate biopsy. METHODS: We relied on 40 patients suspicious for prostate cancer who underwent standard and TT-derived prostate biopsy. Sensitivity, specificity, positive predictive value, negative predictive value and the area under the curve (AUC) were assessed for the prediction of biopsy results per octant by HistoScanning™, using different HistoScanning™ signal volume cutoffs (>0, >0.2 and >0.5 ml). RESULTS: Overall, 319 octants were analyzed. Of those, 64 (20.1 %) harbored prostate cancer. According to different HistoScanning™ signal volume cutoffs (>0, >0.2 and >0.5 ml), the AUCs for predicting biopsy results were: 0.51, 0.51 and 0.53, respectively. Similarly, the sensitivity, specificity, positive predictive and negative predictive values were: 20.7, 78.2, 17.4 and 81.6 %; 20.7, 82.0, 20.3 and 82.3 %; and 12.1, 94.6, 33.3 and 82.9 %, respectively. CONCLUSIONS: Prediction of biopsy results based on HistoScanning™ signals and TT-derived biopsies was unreliable. Moreover, the AUC of TT-derived biopsies was low and did not improve when additional signal volume cutoffs were applied (>0.2 and >0.5 ml). We cannot recommend a variation of well-established biopsy standards or reduction in biopsy cores based on HistoScanning™ signals.

Prostatitis, other genitourinary infections and prostate cancer: results from a population-based case-control study.

PURPOSE: We relied on a population-based case-control study (PROtEuS) to examine a potential association between the presence of histologically confirmed prostate cancer (PCa) and history of genitourinary infections, e.g., prostatitis, urethritis, orchitis and epididymitis. PATIENTS AND METHODS: Cases were 1933 men with incident PCa, diagnosed across Montreal hospitals between 2005 and 2009. Population controls were 1994 men from the same residential area and age distribution. In-person interviews collected information about socio-demographic characteristics, lifestyle and medical history, e.g., self-reported history of several genitourinary infections, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. RESULTS: After multivariable adjustment, prostatitis was associated with an increased risk of any PCa (OR 1.81 [1.44-2.27]), but not urethritis (OR 1.05 [0.84-1.30]), orchitis (OR 1.28 [0.92-1.78]) or epididymitis (OR 0.98 [0.57-1.68]). The association between prostatitis and PCa was more pronounced for low-grade PCa (Gleason ≤ 6: OR 2.11 [1.61-2.77]; Gleason ≥ 7: OR 1.59 [1.22-2.07]). Adjusting for frequency of physician visits, PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. CONCLUSION: Prostatitis was associated with an increased probability for detecting PCa even after adjustment for frequency of PSA testing and physician visits, but not urethritis, orchitis or epididymitis. These considerations may be helpful in clinical risk stratification of individuals in whom the risk of PCa is pertinent.

Additional elastography-targeted biopsy improves the agreement between biopsy Gleason grade and Gleason grade at radical prostatectomy.

PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) may help to correctly assign Gleason grade at radical prostatectomy (RP) and to compare discriminant properties of systematic biopsy alone (sbx) versus combination with RTE-bx (comb-bx) to distinguish between postoperatively favorable (Gleason 3 + 3, pT2, Nx/0) and postoperatively unfavorable (Gleason ≥4 + 4) prostate cancer (PCa) at RP. PATIENTS AND METHODS: Overall, 259 patients diagnosed with PCa at systematic biopsy in combination with RTE-bx underwent RP between 2008 and 2011. Gleason Score derived from sbx versus comb-bx was compared to the gold-standard RP, and discriminant properties were assessed. Specificity gains were examined for sbx versus comb-bx when the endpoint consisted of postoperatively favorable PCa at RP. Sensitivity gains were examined, when analyses focused on postoperatively unfavorable PCa. RESULTS: Comb-bx resulted in higher correct overall Gleason assignment (68.3 vs. 56.7 %, p = 0.008) than sbx. Similarly, lower rates of undergrading (21.2 vs. 36.3 %, p < 0.001) were recorded. Specificity gains with comb-bx were 10 % (92 vs. 82 %, p = 0.004) for postoperatively favorable PCa. Comb-bx resulted in 31 % sensitivity gains relative to sbx (94 vs. 63 %, p = 0.03), when postoperatively unfavorable PCa was the endpoint. CONCLUSION: The agreement between biopsy and pathology Gleason Score was significantly higher for comb-bx than sbx. Additionally, comb-bx reduced the rate of false positives in the diagnosis of favorable PCa. Rates of correctly classified unfavorable PCa at RP were also higher for comb-bx. Those data indicate that comb-bx is useful in clinical practice.