Bimodal imaging: Detection rate of clinically significant prostate cancer is higher in MRI lesions visible to transrectal ultrasound.

BACKGROUND: To explore the detection rates of clinically significant prostate cancer (csPCa; ISUP ≥2) in patients with a single MRI lesion that is visible or invisible on transrectal ultrasound (TRUS) during biopsy. METHODS: Retrospective analyses of patients who underwent targeted and systematic biopsy of the prostate for one MRI-visible lesion (PI-RADS score ≥ 3) between 2017 and 2022. TRUS-visibility, PI-RADS score, and clinical parameters were recorded prospectively. Univariable and multivariable logistic regression models were used to identify predictors of csPCa. RESULTS: 277 consecutive patients with one MRI-visible lesion were identified. A correlating lesion on TRUS was present in 147/277 (53%). The median age, PSA level, and prostate volume were 68.0 years (IQR: 62.0-73.0), 7.3 ng/ml (IQR: 5.4-10.8) and 45.0 cc (IQR: 32.0-68.0), respectively. Baseline parameters were not significantly different between the two groups. CsPCa was detected in 59/130 (45%) without and in 102/147 (69%) patients with a corresponding TRUS lesion. In multivariable logistic regression analysis predicting csPCa, TRUS-visibility (OR: 2.13, CI: 1.14-4.03, p = 0.02) and PI-RADS score (PI-RADS 4: OR: 7.28, CI: 3.33-17.19; PI-RADS 5: OR: 13.39, CI: 5.27-36.83, p < 0.001) achieved independent predictor status. CONCLUSIONS: Bimodal-visible lesions more often harbored csPCa and were easier to target. TRUS-visibility of MRI lesions is an independent predictor of csPCa. Therefore, education in both modalities is essential. Despite MRI, the ultrasound should still be diligently examined.

PSA-density, DRE, and PI-RADS 5: potential surrogates for omitting biopsy?

OBJECTIVE: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, "PI-RADS 5 patients"). MATERIALS AND METHODS: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated. RESULTS: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63-74) and 8.9 ng/ml (IQR 6.0-13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74-0.83). CONCLUSION: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present.

Size of lymph-node metastases in prostate cancer patients undergoing radical prostatectomy: implication for imaging and oncologic follow-up of 2705 lymph-node positive patients.

BACKGROUND: Despite modern imaging modalities, lymph-node staging before radical prostatectomy (RP) remains challenging in patients with prostate cancer (PCa). The visibility of lymph-node metastases (LNMs) is critically influenced by their size. OBJECTIVE: This study aims to describe the distribution of maximal tumor diameters (i.e., size) in LNMs of pN1-PCa at RP and its consequences on visibility in preoperative imaging and oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: A total of 2705 consecutive patients with pN1-PCa at RP, harboring a cumulative 7510 LNMs, were analyzed. Descriptive and multivariable analyses addressed the risk of micrometastases (MM)-only disease and the visibility of LNMs. Kaplan-Meier curves and Cox analyses were used for biochemical recurrence-free survival (BCRFS) stratified for MM-only disease. RESULTS: The median LNM size was 4.5mm (interquartile range (IQR): 2.0-9.0 mm). Of 7510 LNMs, 1966 (26%) were MM (≤ 2mm). On preoperative imaging, 526 patients (19%) showed suspicious findings (PSMA-PET/CT: 169/344, 49%). In multivariable analysis, prostate-specific antigen (PSA) (OR 0.98), age (OR 1.01), a Gleason score greater than 7 at biopsy (OR 0.73), percentage of positive cores at biopsy (OR 0.36), and neoadjuvant treatment (OR 0.51) emerged as independent predictors for less MM-only disease (p < 0.05). Patients with MM-only disease compared to those harboring larger LNMs had a longer BCRFS (median 60 versus 29 months, p < 0.0001). CONCLUSION: Overall, 26% of LNMs were MM (≤ 2mm). Adverse clinical parameters were inversely associated with MM at RP. Consequently, PSMA-PET/CT did not detect a substantial proportion of LNMs. LNM size and count are relevant for prognosis.

Outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy.

PURPOSE: Excessive vesicourethral anastomotic leak (EVAL) is a rare but severe complication after radical prostatectomy (RP). Epithelialized vesicourethral cavity formation (EVCF) usually develops during prolonged catheterization. To our knowledge, there is no description of postoperative outcomes, complications, or functional assessment of these patients who received conservative therapy after EVAL. METHODS: We identified 70 patients (0.56%) with radiographic evidence of EVCF out of 12,434 patients who received RP in 2016-2020 at our tertiary care center. Postoperative radiographic cystograms (CG) were retrospectively re-examined by two urologists individually. We assessed urinary continence (UC), the need for intervention due to anastomotic stricture formation, urinary tract infection (UTI), and symphysitis during the first year of follow-up post-RP. RESULTS: The median age was 66 years [interquartile range (IQR) 61-70 years], the median body mass index was 27.8 kg/m2 (IQR 25.5-30.3 kg/m2), and the median prostate specific antigen before RP was 7.1 ng/ml (IQR 4.7-11.8 ng/ml). The median catheter insertion time was 44.5 days (IQR 35.2-54 days). One-year continence follow-up was available for 27 patients (38.6%), of which 22 (81.5%) reported the use of ≤ one pad, two patients reported the use of two (7.4%) pads/24 h, and three (11.1%) patients reported use > two pads/24 h. Overall, four (5.7%) patients needed surgical reintervention for anastomotic stricture, eight (11.5%) patients presented with symphysitis, and 55 (77.1%) presented with UTI. CONCLUSION: UC in 81.5% 1-year post-RP suggests that conservative treatment in EVAL is a treatment option with an acceptable outcome on UC and should be considered before reintervention for anastomotic insufficiency.

Targeted Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion Biopsy for Quantitative Gleason 4 Grading Prediction in Radical Prostatectomy Specimens: Implications for Active Surveillance Candidate Selection.

BACKGROUND: Quantitative Gleason grading appears to be a reliable prognostic parameter and provides broader risk stratification then the traditional Gleason grading in patients with prostate cancer (PCa) treated with radical prostatectomy (RP). OBJECTIVE: To determine if quantification of Gleason pattern (GP) 4 for targeted and systematic biopsy (TBx + SBx) cores together with further clinical variables can identify the lowest quantitative GP 4 fraction on RP. DESIGN, SETTING, AND PARTICIPANTS: A total of 548 patients underwent TBx + SBx of the prostate and then RP, with pathology revealing Gleason score 3 + 4, 4 + 3, or 4 + 4 disease. INTERVENTION: TBx + SBx of the prostate followed by RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: GP 4 fraction thresholds of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% were compared between the TBx + SBx and RP specimens. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy for predicting the GP 4 fraction in the RP specimen were determined. Logistic regression models were used to establish a probabilistic relationship between various combinations of clinical and biopsy variables and the GP 4 fraction in the RP specimen. RESULTS AND LIMITATIONS: GP 4 fractions of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% was observed in 33%, 49%, 58%, 65%, and 70% of patients on TBx, and 18%, 41%, 53%, 63%, and 70% of patients on RP, respectively. The sensitivity, specificity, NPV, PPV, and accuracy were 75%, 67%, 91%, 39%, and 74% for a TBx GP 4 fraction of ≤5%, and 65%, 85%, 65%, 85%, and 79% for a TBx GP 4 fraction of ≤25%, respectively. A model combining quantified TBx + SBx GP 4 with clinical parameters demonstrated the highest diagnostic accuracy. Limitations include the retrospective study design. CONCLUSIONS: Our results demonstrate that the combination of MRI-TBx + SBx and GP 4 quantification allowed precise detection of a low fraction of GP 4 when using RP specimens as the reference standard. Moreover, we found that clinical variables including Prostate Imaging-Reporting and Data System score without biopsy are limited in detection of low GP 4 fractions. PATIENT SUMMARY: Combination of targeted biopsy alone as well as combined with systematic biopsy and quantitative Gleason grading of biopsy specimen showed high agreement with pathology findings after surgical removal of the prostate. This could help in identifying patients who are suitable for active surveillance.

Suitability of conventional systematic vs. MRI-guided targeted biopsy approaches to assess surgical treatment delay for radical prostatectomy.

OBJECTIVES: To assess if systematic (SBx) vs. transrectal or transperineal mpMRI-ultrasound targeted combined with systematic (TBx + SBx) biopsy confer different effects on treatment delay to radical prostatectomy measured as Gleason grade group (GGG) upgrade of prostate cancer (PCa). MATERIALS AND METHODS: We relied on a multi-institutional cohort of localized PCa patients who underwent RP in Martini-Klinik, Hamburg, or Prostate Center Northwest, Gronau, between 2014 and 2022. Analyses were restricted to PCa GGG 1-3 diagnosed at SBx (n = 4475) or TBx + SBx (n = 1282). Multivariable logistic regression modeling (MVA) predicting RP GGG upgrade of ≥ 1 was performed separately for SBx and TBx + SBx. RESULTS: Treatment delay to RP of < 90, 90-180 and 180-365 days was reported in 59%, 35% and 6.2% of SBx and in 60%, 34% and 5.9% of the TBx + SBx patients, respectively. Upgrade to GGG ≥ 4 at RP was detected in 15% of SBx patients and 0.86% of TBx patients. In MVA performed for SBx, treatment delay yielded independent predictor status (OR 1.17 95% CI 1.02-1.39, p = 0.028), whereas for TBx + SBx MVA, statistical significance was not achieved. CONCLUSION: Treatment delay remained independently associated with radical prostatectomy GGG upgrade after adjustment for clinical variables in the patients diagnosed with SBx alone, but not in those who received combined TBx + SBx. These findings can be explained through inherent misclassification rates of SBx, potentially obfuscating historical observations of natural PCa progression and potential dangers of treatment delay. Thus, mpMRI-guided combined TBx + SBx appears mandatory for prospective delay-based examinations of PCa.

Precision-guidance vs Systematic Sampling: Optimizing Biopsy Assessment of Secondary Prostate Cancer Suspicious Multiparametric Magnetic Resonance Imaging Lesions.

PURPOSE: We assessed the diagnostic yield of consecutive transperineal targeted biopsy of multiparametric magnetic resonance imaging index lesion and secondary lesion and additive systematic biopsy in patients who received combined targeted biopsy+systematic biopsy of prostate. MATERIALS AND METHODS: Of 1,467 patients with targeted biopsy+systematic biopsy, analyses were restricted to 571 patients with index lesion+secondary lesion, Prostate Imaging-Reporting and Data System score ≥3. Index lesion was defined as having the greatest Prostate Imaging-Reporting and Data System score and/or lesion volume as opposed to secondary lesion. We retrospectively compared clinically significant prostate cancer rates (ie, Gleason Grade Group ≥2) between index lesion+secondary lesion and index lesion+secondary lesion+systematic biopsy. Subgroup analyses in men with ipsilateral index lesion+secondary lesion focused on contralateral systematic biopsy. Multivariable logistic regression analyses to predict any clinically significant prostate cancer included age, previous biopsies, prostate specific antigen density, respective index lesion/secondary lesion volumes, side relation, Prostate Imaging-Reporting and Data System strata, and number of targeted biopsy and systematic biopsy cores. RESULTS: Clinically significant prostate cancer rates for index lesion+secondary lesion vs index lesion+secondary lesion+systematic biopsy were 38% vs 42% (P = .2) at expense of significantly higher median number of biopsy cores (9 vs 25, P < .001). In the subgroup with ipsilateral index lesion+secondary lesion (n = 236), contralateral systematic biopsy detected clinically significant prostate cancer in 17%. In the narrower subgroup with ipsilateral index lesion+secondary lesion (n = 131) without any clinically significant prostate cancer, contralateral systematic biopsy detected clinically significant prostate cancer in 3.8%. Multivariable logistic regression analyses confirmed contralateral systematic biopsy as independent predictor, but performed similarly without systematic biopsy information (area under the curve 87.1% vs 86.6%). CONCLUSIONS: Targeted biopsy of secondary lesion should be included in targeted biopsy protocols due to added diagnostic information. However, for targeted biopsy of index lesion+secondary lesion additional systematic biopsy is of limited informative value in terms of overall clinically significant prostate cancer detection. However, when index lesion+secondary lesion are ipsilateral, contralateral systematic biopsy should be recommended for purpose of prostate lobe information. Our results indicate great potential to reduce systematic biopsy cores and associated potential morbidity, and warrant prospective evaluation.

Pan-segmental intraprostatic lesions involving mid-gland and apex of prostate (mid-apical lesions): assessing the true value of extreme apical biopsy cores.

OBJECTIVE: When considering increased morbidity of apical biopsies, the added diagnostic value of separate targeting of mid-gland and apical segment of the pan-segmental mid-apical mpMRI prostate cancer (PCa) suspicious lesions was assessed. MATERIALS AND METHODS: A total of 420 patients with a single mpMRI PCa-suspicious PI-RADS ≥ 3 intraprostatic lesion extending from the mid-gland to the apical segment of the gland underwent transrectal MRI-targeted (TBx) and systematic prostate biopsy. Clinically significant PCa (CsPCa) was defined as Gleason Score (GS) ≥ 3 + 4. PCa detection rates of TBx cores were assessed according to targeted anatomical segments. Finally, the diagnostic values of two theoretical TBx protocols utilizing 1-core (A) vs. 2-cores (B) per anatomical segment were compared. RESULTS: TBx within the pan-segmental mid-apical lesions yielded 44% of csPCa. After stratification into mid- vs. apical segment of the lesion, csPCa was detected in 36% (mid-gland) and 32% (apex), respectively. Within the patients who had no csPCa detection by mid-gland sampling (64%, n = 270), extreme apical TBx yielded additional 8.1% of csPCa. Comparison of extreme apical TBx strategy B vs. overall PCa detection in our cohort revealed corresponding similar rates of 49 vs.50% and 31 vs.32%, respectively. CONCLUSION: Separate analyses of both segments, mid-gland and apex, clearly revealed the diagnostic contribution of apical TBx. Our findings strongly suggest to perform extreme apical TBx even within pan-segmental lesions. Moreover, our results indicate that a higher number of cores sampled from the mid-gland segment might be avoided if complemented with a two-core extreme apical TBx.

Impact of obesity on perioperative, functional and oncological outcomes after robotic-assisted radical prostatectomy in a high-volume center.

OBJECTIVE: To compare surgical, oncological and functional outcomes between obese vs. normal-weight prostate cancer (PCa) patients treated with robotic-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We assessed 4555 consecutive RARP patients from a high-volume center 2008-2018. Analyses were restricted to normal-weight vs. obese patients (≥ 30 kg/m2). Multivariable cox regression analyses (MVA) assessed the effect of obesity on biochemical recurrence (BCR), metastatic progression (MP), erectile function and urinary continence recovery. Analyses were repeated after propensity score matching. RESULTS: Before matching, higher rates of pathological Gleason Grade group ≥ 4 (14 vs. 18%; p = 0.004) and pT3 stage (33 vs. 35%; p = 0.016) were observed in obese patients, with similar observations for surgery time, blood loss and 30-day wound- and surgical complication rates. For normal-weight vs. obese patients, BCR- and MP-free rates were 86 vs. 85% (p = 0.97) and 97.5 vs.97.8% (p = 0.8) at 48 months. Similarly, rates of erectile function at 36 months and urinary continence at 12 months were 56 vs. 49% (p = 0.012) and 88 vs. 85% (p = 0.003), respectively. Before and after propensity score matching, obesity had no effect on BCR or MP, but a negative effect on erectile function (matched HR 0.87, 95%CI 0.76-0.99; p = 0.029) and urinary continence recovery (matched HR 0.91, 95%CI 0.84-0.98; p = 0.014). CONCLUSIONS: Obesity did not represent a risk factor of BCR or MP after RARP despite higher rates of adverse pathological features. However, obesity was associated with higher risk of perioperative morbidity and impaired functional outcomes. Such information is integral for patient counselling. Thus, weight loss before RARP should be encouraged.

Oncologic impact of concomitant prostate cancer characteristics at the time of radical cystoprostatectomy for bladder cancer: a population-based analysis.

OBJECTIVE: The aim of this study was to evaluate the prognostic impact of concomitant prostate cancer (PCa) of the cancer-specific mortality (CSM) in the aging patient's papulation with bladder cancer (BCa) treated with radical cystoprostatectomy (RCP). MATERIALS AND METHODS: Within the SEER database (2004-2015), 1468 patients were treated with RCP for BCa harboring histopathological PCa findings. To account for other cause mortality (OCM), multivariable competing risk regression (CRR) tested for potential BCa-CSM differences according to PCa characteristics risk factors predicting CSM. RESULTS: CRR analysis revealed that only following BCa characteristics, as high pathological tumor stages(Ta/Tis/T1 [REF.] vs. T2; HR 2.03, 95% CI: 1.16-3.57, p = 0.014 vs. T3; HR 4.32, 95% CI: 2.45-7.61, p < 0.001 vs. T4; HR 5.06, 95% CI: 2.77-9.22, p < 0.001), as well unfavorable BCa grade IV (Grade I-II [REF.] vs. Grade IV; HR 0.58, 95% CI: 0.35-0.98, p < 0.041) achieved independent predictor status of CSM. With regard to PCa characteristics, none of the covariates yielded independent predictor status of CSM. CONCLUSIONS: Our study, based on the largest population cohort, demonstrates that even in organ-confined BCa patients, concomitant PCa as second malignancy does not represent a risk factor for survival.

Two-year quality of life after robot-assisted radical prostatectomy according to pentafecta criteria and cancer of the prostate risk assessment (CAPRA-S).

The quality of life (QoL) of men with optimal outcomes after robot-assisted radical prostatectomy (RARP) is largely unexplored. Thus we assessed meaningful changes of QoL measured with the EORTC QLQ-C30 24 months after RARP according to postsurgical Cancer of the Prostate Risk Assessment score (CAPRA-S) and pentafecta criteria. 2871 prostate cancer (PCa) patients with completed EORTC QLQ-C30 were stratified according to CAPRA-S, pentafecta (erectile function recovery, urinary continence recovery, biochemical-recurrence-free survival (BFS), negative surgical margins) and 90-day Clavien-Dindo-complications (CDC) ≤ 3a. Multivariable logistic regression analyses (LRM) aimed to predict improvement of EORTC QoL. Mean preoperative QoL values did not significantly differ between CAPRA-S low- (LR) vs. high-risk (HR, 75.7 vs. 75.2; p = 0.7) and pentafecta vs. non-pentafecta groups (75.6 vs. 75.2; p = 0.6). After RARP, stable QoL rates for CAPRA-S LR vs. HR and pentafecta were 30, 26 and 30%, respectively. Corresponding improved QoL rates were 44, 32 and 47%. In LRM, CAPRA-S and pentafecta criteria were independent predictors of improved QoL. We conclude that most favourable combined outcomes after RARP might confer stable or even improved QoL but up to one third of patients might experience deterioration. This warrants further investigation how to capture the underlying cause and to address and potentially solve these perceived negative effects despite successful RARP.

Optimizing Combined Magnetic Resonance Imaging (MRI)-Targeted and Systematic Biopsy Strategies: Sparing the Multiparametric MRI-Negative Transitional Zone in Presence of Exclusively Peripheral Multiparametric MRI-Suspect Lesions.

PURPOSE: We assessed whether sampling of the transitional zone can be spared in patients with exclusively peripheral prostate cancer (PCa)-suspicious multiparametric magnetic resonance imaging (mpMRI) lesions who undergo combined mpMRI targeted (TBx) and systematic prostate biopsies (SBx). MATERIALS AND METHODS: Of 1,685 patients who underwent extended SBx including transitional zone sampling and had TBx of ≥1 lesion in the peripheral and/or transitional zone, we selected 863 patients with exclusively peripheral PCa-suspicious lesions and negative transitional zone mpMRI. Clinically significant PCa (csPCa) was defined as Gleason score (GS) ≥3+4. Within the selected cohort we performed a retrospective head-to-head comparison of csPCa detection rates between biopsy protocols: A) combination of peripheral TBx plus extended SBx including transitional zone sampling vs B) peripheral TBx plus SBx without any transitional zone sampling. Analyses were complemented with multivariable logistic regression models (LRMs) in the total cohort for predicting csPCa in SBx transitional zone sampling. RESULTS: Compared to the extended protocol (A), omission of systematic transitional zone sampling (B) yielded similar PCa detection for csPCa (48% vs 47%) and GS 3+3 (21% vs 20%). Only 2.0% csPCa was additionally detected with transitional zone SBx sampling (A). LRM confirmed that intraprostatic zonal distribution of mpMRI lesions independently influences csPCa detection rates of transitional zone SBx sampling. CONCLUSIONS: A peripheral TBx plus SBx without any transitional zone sampling protocol (B) yields similar csPCa detection rates as the standard extended protocol (A) but may reduce biopsy-related morbidity. This zone-dependent biopsy strategy warrants prospective evaluation to optimize the extent of systematic biopsies in presence of suspicious mpMRI lesions.

Twenty-year trends in prostate cancer stage and grade migration in a large contemporary german radical prostatectomy cohort.

BACKGROUND: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports. MATERIAL AND METHODS: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy. RESULTS: Absolute rates of D'Amico low risk decreased (-30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (-50.0%), while GGG II-V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were -1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between -0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001). CONCLUSION: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.

Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study.

Objective: Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. Methods: Overall, 275 patients from 8 European neurological centers were examined. We included ALS with <6 and >6 months from symptom onset, other motoneuron diseases (oMND), ALS mimics (DCon) and non-neurodegenerative controls (Con). CSF CHIT1 levels were analyzed for diagnostic power and association with progression and survival in comparison to the benchmark neurofilament. The 24-bp duplication polymorphism of CHIT1 was analyzed in a subset of patients (N = 65). Results: Homozygous CHIT1 duplication mutation carriers (9%) invariably had undetectable CSF CHIT1 levels, while heterozygous carriers had similar levels as patients with wildtype CHIT1 (p = 0.414). In both early and late symptomatic ALS CHIT1 levels was increased, did not correlate with patients' progression rates, and was higher in patients diagnosed with higher diagnostic certainty. Neurofilament levels correlated with CHIT1 levels and prevailed over CHIT1 regarding diagnostic performance. Both CHIT1 and neurofilaments were identified as independent predictors of survival in late but not early symptomatic ALS. Evidence is provided that CHIT1 predicts progression in El Escorial diagnostic category in the group of ALS cases with a short duration. Conclusions: CSF CHIT1 level may have additional value in the prognostication of ALS patients with a short history of symptoms classified in diagnostic categories of lower clinical certainty. To fully interpret apparently low CHIT1 levels knowledge of CHIT1 genotype is needed.

Combined systematic versus stand-alone multiparametric MRI-guided targeted fusion biopsy: nomogram prediction of non-organ-confined prostate cancer.

OBJECTIVE: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx). MATERIALS AND METHODS: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3). RESULTS: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3. CONCLUSION: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.

Minimum Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy Cores Needed for Prostate Cancer Detection: Multivariable Retrospective, Lesion Based Analyses of Patients Treated with Radical Prostatectomy.

PURPOSE: We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer. RESULTS: In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer. CONCLUSIONS: Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.

Rectal Swabs for Detecting Multidrug Resistant Bacteria Prior to Transrectal Prostate Fusion Biopsy: A Prospective Evaluation of Risk Factor Screening and Microbiologic Findings.

OBJECTIVE: To assess the prevalence of fluoroquinolone resistant (QR) bacteria, multidrug resistant (MDR) bacteria and Enterococcus faecalis (E. faecalis) in rectal swabs of patients undergoing transrectal prostate biopsy and for evaluating if risk factor assessment is reliable for prediction of QR bacteria, MDR bacteria, or E. faecalis. PATIENTS AND METHODS: Two hundred consecutive patients received a rectal swab examination prior to transrectal magnetic resonance imaging-guided fusion biopsy, for evaluating the prevalence of QR bacteria, MDR bacteria, and E. faecalis. The results of a standardized risk factor questionnaire, assessing known prognosticators for higher prevalence of resistant bacteria in rectal flora were correlated with the occurrence of QR bacteria, MDR bacteria, and E. faecalis in rectal swabs. RESULTS: QR E. coli was detected in 12 patients (6%). Regarding MDR bacteria, extended spectrum ß- lactamase- producing E. coli occurred in 8 patients (4%). E. faecalis was found in 15 patients (7.5%). A total of 193 patients completed the risk factor questionnaire. Of those, 107 (53.2%) patients harbored no risk factors, while 86 (42.8%) had at least 1 risk factor, of which the most common was repeat biopsy. No association was found between any risk factor and occurrence of QR bacteria, MDR bacteria, or E. faecalis (P >.05). CONCLUSION: The prevalence of resistant germs in our cohort was lower compared to other series. Moreover, the rate of QR bacteria, MDR bacteria, or E. faecalis in rectal swabs was not reliably associated with risk factor assessment.

Prediction of Complications in Radical Prostatectomy Prostate Cancer Patients: Simulated Annealing versus Co-Morbidity Indexes.

BACKGROUND: The Deyo/Charlson co-morbidity index (CCI) and Klabunde co-morbidity index (KCI) co-morbidity indexes represent outdated indexes when the endpoint of complications after radical prostatectomy (RP) is considered. A novel group of co-morbidities derived from International Classification of Diseases-9 diagnostic codes in a contemporary RP database could provide better accuracy. Research Design, Subjects and Measures: We relied on 20,484 patients with clinically localized non-metastatic prostate cancer treated with RP between 2000 and 2009 in the Surveillance, Epidemiology, and End Results-Medicare linked database. We examined 2 endpoints, namely, 90-day medical complication rate and 90-day surgical complication rate after RP. Simulated annealing (SA) was used to develop a novel co-morbidity index. Finally, the newly identified groups of co-morbid conditions were compared with the CCI and Klabunde indexes. RESULTS: Our SA identified 10 and 7 individual co-morbid conditions able to predict 90-day medical and surgical complications respectively. This novel model showed improved predictive accuracy over CCI and KCI for the 2 endpoints considered (respectively: 59.4 vs. 58.1 and 58.0% for medical complications, 58.0 vs. 56.8 and 56.7% for surgical complications). CONCLUSIONS: The newly defined groupings of co-morbid conditions resulted in better ability to predict the 2 endpoints of interest compared to CCI and KCI. However, the gain was marginal. This implies that better tools should be defined to more accurately predict these outcomes.

Anterior Localization of Prostate Cancer Suspicious Lesions in 1,161 Patients Undergoing Magnetic Resonance Imaging/Ultrasound Fusion Guided Targeted Biopsies.

PURPOSE: Based on findings in transrectal ultrasound guided biopsy series standard sampling of the prostate targets the posterior/peripheral zone. However, a substantial proportion of lesions that are prostate cancer suspicious and PI-RADS™ (Prostate Imaging Reporting and Data System) 3 or greater on magnetic resonance imaging is located in the anterior segment of the prostate, requiring deeper placement and targeting of the biopsy needle. MATERIALS AND METHODS: Overall 1,161 patients underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy. Prostate cancer suspicious lesions on magnetic resonance imaging were dichotomized into anterior vs posterior prostate segments. Patients were stratified by the number of prior negative systematic biopsy sessions. Descriptive statistics included the frequency and proportion of multiparametric magnetic resonance imaging findings and corresponding histological results. RESULTS: Targeted biopsy was performed in 513 patients (44%) who were systematic biopsy naïve, 396 (34%) with 1 prior negative systematic biopsy and 252 (22%) with 2 or more prior negative systematic biopsies. When patients were stratified by the number of prior systematic biopsy sessions, the proportion with exclusively anterior, PI-RADS 3 or greater lesions on magnetic resonance imaging increased from 3.5% to 9.1% (p = 0.006). Unfavorable 3 + 4 and 4 + 3 or greater primary Gleason patterns were identified in exclusively anterior vs posterior lesions in 31% vs 21% of the 448 patients, of whom 64 had exclusively anterior and 384 had posterior PI-RADS 3 or greater lesions, respectively, on magnetic resonance imaging. Multivariable logistic regression analyses confirmed these findings. CONCLUSIONS: After multiple previous negative systematic biopsy sessions the proportion of anterior lesions on magnetic resonance imaging increased. Such lesions harbored a greater amount of unfavorable prostate cancer. Therefore, image guidance for precise targeting should be considered, especially after initially negative transrectal ultrasound guided systematic biopsy.