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.

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.

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.

Diagnostic Accuracy of Magnetometer-Guided Sentinel Lymphadenectomy After Intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles in Intermediate- and High-Risk Prostate Cancer Using the Magnetic Activity of Sentinel Nodes.

Due to the high morbidity of extended lymph node dissection (eLND) and the low detection rate of limited lymph node dissection (LND), targeted sentinel lymph node dissection (sLND) was implemented in prostate cancer (PCa). Subsequently, nonradioactive sentinel lymph node (SLN) detection using magnetic resonance imaging (MRI) and a magnetometer after intraprostatic injection of superparamagnetic iron oxide nanoparticles (SPIONs) was successfully applied in PCa. To validate the reliability of this approach, considering the magnetic activity of SLNs or whether it is sufficient to dissect only the most active SLNs as shown in other tumor entities for radio-guided sLND, we analyzed magnetometer-guided sLND results in 218 high- and intermediate-risk PCa patients undergoing eLND as a reference standard. Using a sentinel nomogram to predict lymph node invasion (LNI), a risk range was determined up to which LND could be dispensed with or sLND only would be adequate. In total, 3,711 LNs were dissected, and 1,779 SLNs (median, 8) were identified. Among 78 LN-positive patients, there were 264 LN metastases (median, 2). sLND had a 96.79% diagnostic rate, 88.16% sensitivity, 98.59% specificity, 97.1% positive predictive value (PPV), 93.96% negative predictive value (NPV), 4.13% false-negative rate, and 0.92% additional diagnostic value (LN metastases only outside the eLND template). For intermediate-risk patients only, the sensitivity, specificity, PPV, and NPV were 100%. Magnetic activities of SLNs were heterogeneous regardless of metastasis. The accuracy of predicting the presence of metastases for each LN from the proportion of activity was only 57.3% in high- and 65% in intermediate-risk patients. Patients with LNI risk of less than 5% could have been spared LND, as no positive LNs were found in this group. For patients with an LNI risk between 5% and 20%, sLND-only would have been sufficient to detect almost all LN metastases; thus, eLND could be dispensed with in 36% of patients. In conclusion, SPION-guided sLND is a reliable alternative to eLND in intermediate-/high-risk PCa. No conclusions can be drawn from magnetic SLN activity regarding the presence of metastases. LND could be dispensed with according to a nomogram of predicted probability for LNI of 5% without losing any LN-positive patient. Patients with LNI risk between 5% and 20% could be spared eLND by performing sLND.

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.

Assessment of Oncological Outcomes After Radical Prostatectomy According to Preoperative and Postoperative Cancer of the Prostate Risk Assessment Scores: Results from a Large, Two-center Experience.

BACKGROUND: Among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) and with virtually identical unfavorable pathological characteristics, those deemed at low risk (LR) preoperatively had better oncological outcomes than those with intermediate (IR) or high risk (HR) preoperatively. OBJECTIVE: To examine if this phenomenon still applies when preoperative Cancer of the Prostate Risk Assessment (CAPRA) scores are compared to postoperative scores (CAPRA-S) in RP patients. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 10 290 PCa patients who underwent RP at tertiary care centers in Hamburg (Germany) and Milan (Italy) during 1991-2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All patients were classified as CAPRA/CAPRA-S LR, IR, or HR (≤2, 3-5, and ≥6 points, respectively). Kaplan-Meier and Cox regression analyses were performed to assess the risk of biochemical recurrence (BCR) and metastatic disease (metD). RESULTS AND LIMITATIONS: Overall, 59.6%, 29.3%, and 11.1% patients were CAPRA-S LR, IR, and HR respectively. For CAPRA-S LR patients, 5-yr BCR-free and metD-free rates for preoperative CAPRA LR versus IR/HR patients were 93.1% versus 85.7% (p<0.001) and 99.7% versus 98.9% (p=0.017), respectively. For CAPRA-S IR/HR patients, the corresponding rates were 69.9% versus 57.2% and 98.2 versus 93.7% (both p<0.001). On multivariable Cox regression analyses, a combination of CAPRA-S and preoperative CAPRA resulted in increases in predictive accuracy for BCR (from 76.0% to 78.3%) and metD (from 82.0% to 84.0%). Specifically, biopsy Gleason patterns and the percentage of positive cores added information to the CAPRA-S score. Long-term follow-up is needed to discern clinical metD differences between preoperative CAPRA risk groups. CONCLUSIONS: CAPRA-S LR patients in the CAPRA IR/HR group had higher BCR/metD risk. Conversely, CAPRA-S IR/HR patients in the CAPRA LR group had lower BCR/metD risk. Future tools should incorporate better tumor and Gleason quantification to optimize prediction. PATIENT SUMMARY: We demonstrated that among 10290 European patients with prostate cancer who underwent radical prostatectomy, those deemed at low risk preoperatively had better oncological outcomes than their peers with intermediate or high risk, despite virtually identical unfavorable pathological characteristics.

Magnetic resonance sentinel lymph node imaging and magnetometer-guided intraoperative detection in prostate cancer using superparamagnetic iron oxide nanoparticles.

PURPOSE: Sentinel lymph node (LN) dissection (sLND) using a magnetometer and superpara-magnetic iron oxide nanoparticles (SPION) as a tracer was successfully applied in prostate cancer (PCa). The feasibility of sentinel LN (SLN) visualization on MRI after intraprostatic SPION injection has been reported. In the present study, results of preoperative MRI identification of SLNs and the outcome of subsequent intraoperative magnetometer-guided sLND following intraprostatic SPION injection were studied in intermediate- and high-risk PCa. PATIENTS AND METHODS: A total of 50 intermediate- and high-risk PCa patients (prostate-specific antigen >10 ng/mL and/or Gleason score ≥7) scheduled for radical prostatectomy with magnetometer-guided sLND and extended pelvic LND (eLND), were included. Patients underwent MRI before and one day after intraprostatic SPION injection using T1-, T2-, and T2*-weighted sequences. Diagnostic rate per patient was established. Distribution of SLNs per anatomic region was registered. Diagnostic accuracy of sLND was assessed by using eLND as a reference standard. RESULTS: SPION-MRI identified a total of 890 SLNs (median 17.5; IQR 12-22.5). SLNs could be successfully detected using MRI in all patients (diagnostic rate 100%). Anatomic SLN distribution: external iliac 19.2%, common iliac 16.6%, fossa obturatoria 15.8%, internal iliac 13.8%, presacral 12.1%, perirectal 12.0%, periprostatic 3.7%, perivesical 2.3%, and other regions 4.4%. LN metastases were intraoperatively found in 15 of 50 patients (30%). sLND had a 100% diagnostic rate, 85.7% sensitivity, 97.2% specificity, 92.3% positive predictive value, 94.9% negative predictive value, false negative rate 14.3%, and 2.8% additional diagnostic value (LN metastases only outside the eLND template). CONCLUSION: MR scintigraphy after intraprostatic SPION injection provides a roadmap for intraoperative magnetometer-guided SLN detection and can be useful to characterize a reliable lymphadenectomy template. Draining LN from the prostate can be identified in an unexpectedly high number, especially outside the established eLND template. Further studies are required to analyze discordance between the number of pre- and intraoperatively identified SLNs.

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.

Tumor characteristics, treatments, and oncological outcomes of prostate cancer in men aged ≤50 years: a population-based study.

BACKGROUND: To examine clinical characteristics, treatment modalities and oncological outcomes of prostate cancer (PCa) according to young (≤50) vs. old age. METHODS: Of 407,599 men with primary adenocarcinoma of the prostate within the Surveillance, Epidemiology and End Results (SEER)-database (2004 to 2013), 18,387 were aged ≤50 years (4.5%). Time trends, cumulative incidence, and competing risks regression (CRR) analyses tested for differences between young and old patients. Multi-variable analyses were adjusted for year of diagnosis, race, marital status, Gleason Score, clinical tumor stage, and lymph node status. RESULTS: Younger men had more favorable tumor characteristics: lower Gleason Score, lower median PSA, and lower rates of metastases at diagnosis compared to their older counterparts. Over time, no local treatment (NLT) rates increased, radical prostatectomy (RP), and brachytherapy (BT) rates decreased and external beam radiation (EBRT) rates remained unchanged. Moreover, the rate of de novo metastatic prostate cancer increased in young patients from 2% (2004) to 3.2% (2013) (p = 0.004). CRR models showed no difference in prostate cancer-specific mortality (PCSM) between young and old, across all local treatment types. CONCLUSIONS: Young PCa patients have more favorable disease characteristics at presentation, are less frequently treated with RP or BT and more frequently benefit of NLT. PCSM did not differ between young and old patients. However, it is worrisome that recently more young PCa patients are diagnosed at a metastatic stage.

Adherence to pelvic lymph node dissection recommendations according to the National Comprehensive Cancer Network pelvic lymph node dissection guideline and the D'Amico lymph node invasion risk stratification.

PURPOSE: To assess adherence rates to pelvic lymph node dissection (PLND) according to National Comprehensive Cancer Network (NCCN) PLND guideline (2% or higher risk) and D'Amico lymph node invasion (LNI) risk stratification (intermediate/high risk) in contemporary North American patients with prostate cancer treated with radical prostatectomy (RP). MATERIAL AND METHODS: We relied on 49,358 patients treated with RP and PLND (2010-2013) in SEER database. Adherence rates were quantified and multivariable (MVA) logistic regression analyses tested for independent predictors. RESULTS: According to NCCN PLND guideline and D'Amico LNI classification, PLND was recommended in 63.3% and 64.9% of patients, respectively. Corresponding adherence rates were 68.8% and 69.1%. Adherence rates improved from 67.3% to 71.6% and from 67.6% to 72.0%, respectively, over time. In MVA, more advanced clinical stage, higher biopsy Gleason score and higher number of positive biopsy cores predicted PLNDs that were performed below NCCN LNI nomogram risk threshold. Conversely, lower clinical stage, lower PSA and lower biopsy Gleason score predicted PLND omission in individuals with risk level above NCCN LNI nomogram risk threshold. MVA results for D'Amico classification were virtually identical. CONCLUSIONS: Adherence to NCCN PLND guideline and D'Amico LNI classification for purpose of PLND is suboptimal in SEER population-based patients treated with RP. However, adherence rates have improved over time. Patients, who did not undergo PLND despite elevated LNI risk, had more favorable PCa characteristics than the average. Conversely, patients, who underwent PLND despite low-risk, had worse PCa characteristics than the average.

Comparison of 11 Active Surveillance Protocols in Contemporary European Men Treated With Radical Prostatectomy.

BACKGROUND: The aim of this study was to compare 11 active surveillance (AS) protocols in contemporary European men treated with radical prostatectomy (RP) at the Martini-Clinic Prostate Cancer Center. PATIENTS AND METHODS: Analyzed were 3498 RP patients, from 2005 to 2016, who underwent ≥ 10 core biopsies and fulfilled at least 1 of 11 examined AS entry definitions. We tested proportions of AS eligibility, ineligibility, presence of primary Gleason 4/5, upstage, and combinations thereof at RP, as well as 5-year biochemical recurrence-free survival (BFS). RESULTS: The most and least stringent criteria were very low risk National Comprehensive Cancer Network and Royal Marsden with 18.8% and 96.1% of AS-eligible patients, respectively. Rates of primary Gleason 4/5 at RP, upstaging, or both features, respectively, ranged from 2.3% to 6.7%, 6.1% to 18.2%, and 7.1% to 21.0% for those 2 AS entry definitions. The range of individuals deemed AS-ineligible between the same 2 AS entry definitions, despite not harboring unfavorable pathology (primary Gleason pattern 4/5, upstage, or both), was 80.3% to 3.7%, 78.3% to 3.4%, and 77.8% to 3.4%, respectively. BFS rates showed narrow variability, with a range of 85.9% to 91.8%. CONCLUSION: Use of stringent AS entry definitions reduces the number of AS-eligible patients, which is related to a select range in individual entry parameters. Moreover, rates of unfavorable pathology at RP as much as tripled between most and least stringent AS entry definitions. However, less stringent AS entry definitions result in the lowest AS-ineligibility rates, in men without unfavorable pathology. BFS rates were virtually invariably high. Clinicians should know differences in key parameters underlying each AS entry definition, associated effect on rates of eligibility, and potential misclassification of individuals.

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.

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.

Local Therapy Improves Survival in Metastatic Prostate Cancer.

BACKGROUND: Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT). OBJECTIVE: To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results database (2004-2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses. RESULTS AND LIMITATIONS: Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n=474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32-0.50) versus NLT (n=1896). In MVA CRR after PSM, RP (n=161) results in lower CSM (SHR 0.59, 95% CI 0.35-0.99) versus RT (n=161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR=5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective. CONCLUSIONS: In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits. PATIENT SUMMARY: Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy.

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.

Radical prostatectomy neutralizes obesity-driven risk of prostate cancer progression.

INTRODUCTION: Obesity negatively affects several prostate cancer (PCa) outcomes, including mortality to PCa. However, the validity of several such associations is still under debate, including its effect on pathological stage at radical prostatectomy (RP) and subsequent biochemical recurrence (BCR), which represents the focus of this study. METHODS: We relied on patients with PCa treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable logistic regression analyses tested for association between obesity and non-organ-confined disease (≥pT3 or pN1). Second, multivariable Cox regression analyses examined obesity effect on BCR. Last, in a propensity score-matched cohort, Kaplan-Meier analyses assessed BCR-free survival according to body mass index (kg/m2) (BMI) strata (≥30 vs.<25). RESULTS: Of 16,014 individuals, 2,403 (15%) men were obese (BMI≥30). Median follow-up was 36.4 months (interquartile range: 13.3-60.8). Obese patients were more likely to harbor non-organ-confined disease at final pathology (odds ratio = 1.27; 95% CI: 1.13-1.43; P<0.001) but did not have higher BCR rates (hazard ratio = 0.98; 95% CI: 0.86-1.11; P = 0.7). Similarly, BCR-free survival was not different between obese and nonobese men, after propensity score matching (log rank P = 0.9). CONCLUSION: Obesity (BMI ≥30) might predispose to higher rates of non-organ-confined disease at RP. However, obesity was not an independent predictor of BCR after surgery. Consequently, the unfavorable effect of obesity on PCa might be limited to local spread of the disease and might be neutralized after RP.

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.

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.

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.