Impact of PSA nadir, PSA response and time to PSA nadir on overall survival in real-world setting of metastatic hormone-sensitive prostate cancer patients.

BACKGROUND: To evaluate the impact of prostate-specific antigen (PSA) nadir, PSA response and time to PSA nadir (TTN) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies. METHODS: Different PSA nadir cut-offs (including ultra-low PSA) were tested for OS analyses. Additionally, PSA response ≥99% was evaluated, as well as TTN categorized as <3 versus 3-6 versus 6-12 versus >12 months. Multivariable Cox regression models predicted the value of PSA nadir cut-offs, PSA response and TTN on OS. Sensitivity analyses were performed in de novo and high volume mHSPC patients. RESULTS: Of 238 eligible patients, PSA cut-offs of <0.2 versus 0.2-4.0 versus >4.0 ng/mL differed significantly regarding median OS (96 vs. 56 vs. 44 months, p < 0.01), as well as in subgroup analyses of de novo mHSPC patients and multivariable Cox regression models. A more stringent PSA cut-off of <0.02 versus 0.02-0.2 versus >0.2 ng/mL also yielded significant median OS differences (not reached vs. 96 vs. 50 months, p < 0.01), even after additional multivariable adjustment. A PSA response ≥99% was also significantly associated with better OS than counterparty with <99% response, even after multivariable adjustment (both p < 0.02). When TTN groups were compared, patients with longer TTN harbored more extended OS than those with short TTN (<3 vs. 3-6 vs. 6-12 vs. >12 months: 34 vs. 50 vs. 67 vs. 96 months, p < 0.01). Virtually similar results were observed in sensitivity analyses for high volume mHSPC patients. CONCLUSIONS: In times of combination therapies for mHSPC, a PSA nadir of respectively, <0.2 and <0.02 ng/mL are associated with best OS rates. Moreover, a relative PSA response ≥99% and a longer TTN are clinical important proxies for favorable OS estimates.

Real-world evidence of tumor and patient characteristics and survival with avelumab maintenance after chemotherapy for advanced and metastatic urothelial carcinoma.

PURPOSE: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AE) and survival of avelumab maintenance (AVM) treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). METHODS: We relied on our institutional database to identify mUC patients who received AVM between 01/2021-12/2023. The main outcomes consisted of overall (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to PD-L1 status. RESULTS: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years of which 67% were males. Of these, 63%, 21% and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients, however, were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (CI: 3.2-18.2). Median OS was 13.4 (CI: 6.9-not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1 positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively. CONCLUSION: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in in real-world setting.

Cardiovascular Disease and Chronic Pulmonary Disease Increase the Risk of Short-Term Major Postoperative Complications after Robotic-Assisted Radical Prostatectomy.

Background and objectives: Certain comorbidities may be associated with a higher risk of complications after robotic-assisted radical prostatectomy. Material and Methods: Relying on a tertiary care database, we identified robotic-assisted radical prostatectomy patients (January 2014-March 2023). Short-term major postoperative complications were defined according to Clavien Dindo as ≥IIIa within 30 days after robotic-assisted radical prostatectomy. Results: Of 1148 patients, the rates of postoperative Clavien Dindo IIIa, Clavien Dindo IIIb, Clavien Dindo IVa, and Clavien Dindo IVb complications were 3.3%, 1.4%, 0.3%, and 0.2%, respectively. Of those, 28 (47%) had lymphoceles, and 8 (13%) had bleeding-associated complications. Patients with cardiovascular disease (8 vs. 4%) or chronic pulmonary disease (13 vs. 5%) were more likely to have complications. In multivariable logistic regression models, cardiovascular disease (odds ratio: 1.78; p = 0.046) and chronic pulmonary disease (odds ratio: 3.29; p = 0.007) remained associated with an increased risk of postoperative complications. Conclusions: Complications after robotic-assisted radical prostatectomy are predominantly manageable without anesthesia. Concomitant cardiovascular disease and chronic pulmonary disease were both associated with a higher risk of postoperative complications.

Real-world evidence of outcomes of oligometastatic hormone-sensitive prostate cancer patients treated with metastasis-directed therapy.

OBJECTIVE: To investigate characteristics and outcomes of oligometastatic hormone-sensitive prostate cancer (mHSPC) patients undergoing metastases-directed therapy (MDT) with external beam radiation therapy (EBRT). MATERIALS AND METHODS: We relied on an institutional tertiary-care database to identify mHSPC patients who underwent EBRT as MDT between 12/2019 and 12/2022. Main outcomes consisted of progression to metastatic castration-resistant prostate cancer (mCRPC) and overall mortality (OM). Oligometastatic was defined as ≤3 metastases and bone and/or lymph node deposits were treated with conventional doses up to 54 Gy or with hypofractionated stereotactic regimes of median 24 Gy (20-27 Gy). RESULTS: Overall, 37 patients treated with EBRT as MDT were identified. The median follow-up was 13 months. Median age at MDT was 71 years and 84% exhibited ECOG performance status 0. The median baseline PSA at diagnosis was 10 ng/mL. Overall, primary local therapy consisted of radical prostatectomy (65%), followed by external beam radiation therapy to the prostate (11%), focal therapy (8%), and palliative transurethral resection of the prostate (5%). Overall, 32% exhibited de novo oligometastatic mHSPC. Bone metastases were present in 78% versus 19% lymph node metastases versus 3% both. The distribution of targeted oligo-metastases was 62% versus 38% for respectively one metastasis versus more than one metastasis. Androgen deprivation therapy (ADT) was combined with MDT in 84%. Moreover, 19% received combination therapy with apalutamide/enzalutamide and 12% with abiraterone or docetaxel. The median time to mCRPC was 50 months. In incidence analyses, 13% developed mCRPC after 24 months. OM after 24 months was 15% in mHSPC patients receiving MDT. Significant OM differences were observed after stratification into targeted metastatic burden (<0.05). No high-grade adverse events were recorded during MDT. CONCLUSION: Our real-world data suggest that MDT represents a safe treatment option for well-selected oligometastatic mHSPC patients.

Impact of Age on Long-Term Urinary Continence after Robotic-Assisted Radical Prostatectomy.

Aim and Objectives: We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials: We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results: Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three (p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion: Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

[First clinical and oncological experiences with triplet therapy for high-volume metastatic hormone-sensitive prostate cancer]. / Erste klinische und onkologische Erfahrungen mit der Triplet-Therapie beim "high-volume" metastasierten hormonsensiblen Prostatakarzinom.

BACKGROUND: Treatment with androgen deprivation therapy (ADT) plus extended hormone therapy (ARTA) is the standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). Recent data of triplet combination therapies of ADT + ARTA (abiraterone/darolutamide) + docetaxel chemotherapy showed a survival advantage for specific mHSPC patient subgroups. PURPOSE: What treatment response is observed in real-world mHSPC setting using triplet combination therapy and what are the expected side effects? RESULTS: All patients receiving triplet combination therapy of ADT + ARTA (abiraterone/darolutamide) + docetaxel were included in the current study. A total of 14 patients with a median age of 62 years and 10/14 abiraterone or 4/14 darolutamide therapy could be included. The median PSA before initiation of therapy was 77 ng/ml (IQR 44-150). Overall, 86% of patients had a PSA response > 90% and the median PSA nadir was 0.3 ng/ml. Severe adverse events (grade III) during triplet therapy occurred in two patients (35,7%) with respectively febrile neutropenia 7.1% (1/14) and diarrhea with infection 7.1%. Other low grade adverse events (grade I/II) consisted of polyneuropathy (1/14), mucositis (1/14), xerostomia (1/14), weight loss (1/14) and fatigue (3/14) were detected. Chemotherapy was interrupted in one patient due to adverse events. After a median follow-up of ten months (IQR: 7-17), two patients (14.2%) showed progression to castration resistance. CONCLUSION: Triplet therapy shows a very good PSA response in clinical practice. Adverse events during therapy are mainly triggered by classical chemotherapy-known side effects.

Transition from Transrectal to Transperineal MRI-Fusion Prostate Biopsy Does Not Comprise Detection Rates of Clinically Significant Prostate Cancer at a Tertiary Care Center.

BACKGROUND: A remarkable paradigm shift has emerged regarding the preferred prostate biopsy approach, favoring the transperineal (TP) over the transrectal (TR) approach due to the reduced risk of severe urinary tract infections. However, its impact on the detection of clinically significant prostate cancer (csPCa) remains unclear. MATERIALS AND METHODS: We relied on a prospectively maintained tertiary care database to identify patients who underwent either TP or TR prostate biopsy between 01/2014 and 12/2023. Of those, only patients with suspicious magnetic resonance imaging (MRI) PIRADS lesions (Likert-scale: 3,4,5) received MRI-targeted and systematic biopsies. Detection rates of csPCa (International Society of Urological Pathology [ISUP] ≥ 2) were compared between biopsy approach (TP vs. TR) according to index lesion. Subsequently, uni- and multivariable logistic regression models were applied to investigate the predictive status of the biopsy approach within each subcohort. RESULTS: Of 2063 patients, 1118 (54%) underwent combined MRI-guided and systematic prostate biopsy and were included in the final cohort. Of those, 127 (11%) and 991 (89%) underwent TP vs. TR. CsPCa rates, regardless of differences in patients' demographics and distribution of index PIRDAS lesions, did not differ statistically significantly and were 51 vs. 52%, respectively (p = 0.8). CsPCa detection rates for PIRDAS-3, PIRADS-4 and PIRADS-5 did not differ and were 24 vs. 23%, 48 vs. 51% and 72 vs. 76% for PIRADS-3, PIRADS-4 and PIRADS-5 subgroups for TP vs. TR, respectively (all p ≥ 0.9) Conclusions: The current results support the available data indicating that TP biopsy approach is comparable to transrectal biopsy approach regarding csPCa detection rates.

Treatment patterns and oncological outcomes of older adults with metastatic prostate cancer in real-world setting.

BACKGROUND: The landscape of systemic therapies for metastatic hormone-sensitive (mHSPC) and castration resistant prostate cancer (mCRPC) extensively improved within the last decades resulting in a significantly prolonged overall survival. However, subgroup analyses of phase III trials suggest potentially different overall survival outcomes for older adults. METHODS: We relied on our institutional metastatic prostate cancer database to identify mHSPC and subsequently mCRPC patients. Older adults were stratified according to age groups 70-74 versus ≥75-79 versus ≥80 years at metastatic occurrence. Subsequently, uni- and multivariable time to mCRPC and overall survival analyses were performed. RESULTS: Of 494 older adults, 217 (44%) were 70-74 versus 180 (36%) 75-79 versus 97 (20%) ≥80 years old. Rates of local prostate cancer treatment differed significantly between all three groups (p < 0.01). Regarding mHSPC treatment, androgen receptor signaling inhibitors (ARSI) were administered in 30-39% of patients and docetaxel with 9% in age group 70-74 years and 6% and 3% in age groups 75-79 years and ≥80 years. Regarding mCRPC treatment, significant differences between treatment proportions were observed (p < 0.01). Most common treatment was ARSI for all three groups. Conversely, chemotherapy was more frequently administered in patients aged 70-74 (16%), relative to 4% and 3% in 75-79 year and ≥80 year aged patients. In univariable and multivariable time to mCRPC analyses, overall survival in mHSPC and OS in mCRPC analyses, no significant differences between all three age groups were observed (all p ≥ 0.3). CONCLUSIONS: Treatment patterns differ significantly between older adults with metastatic prostate cancer. However, these differences may not result in differences of overall life expectancy.

Feasibility of Next-generation Sequencing of Liquid Biopsy (Circulating Tumor DNA) Samples and Tumor Tissue from Patients with Metastatic Prostate Cancer in a Real-world Clinical Setting in Germany.

BACKGROUND AND OBJECTIVE: With European Medicines Agency approval of PARP inhibitors in metastatic castration-resistant prostate cancer and ongoing trials in metastatic hormone-sensitive prostate cancer, detection of genetic alterations in BRCA1/2 and other homologous recombination repair genes has gained an important role. Our aim was to investigate the feasibility and comparability of comprehensive next-generation sequencing (NGS) of liquid biopsy (LB; circulating tumor DNA) and tumor tissue (TT) samples in a real-world clinical setting. METHODS: The study cohort consisted of 50 patients with metastatic prostate cancer (mPC) who had TT NGS performed for BRCA1/2 alterations and consent for additional LB NGS. The Oncomine Comprehensive Assay v3 (Thermo Fisher Scientific, Waltham, MA, USA) was used for TT NGS. The Guardant360 83-gene assay (Guardant Health, Palo Alto, CA, USA) was used for LB NGS, including all types of somatic alterations, microsatellite instability, and blood tumor mutational burden. We calculated BRCA1/2 alteration rates and the negative percentage agreement (NPA) and positive percentage agreement (PPA) between TT and LB results. KEY FINDINGS AND LIMITATIONS: TT NGS was successful in 44/50 patients (88%), with pathogenic BRCA1/2 alterations detected in four (9%). LB NGS was successful in all 50 patients (100%), with BRCA1/2 alterations detected in ten (20%). In a subgroup analysis for the 44 patients with successful TT NGS, NPA was 85% and PPA was 50%. The median time between TT sample collection and blood sampling for NGS was 132 wk (IQR 94-186). The limited sample size and differences in the time of NGS assessment are limitations. CONCLUSIONS AND CLINICAL IMPLICATIONS: LB NGS resulted in a higher detection rate for BRCA1/2 alterations in comparison to conventional TT NGS (20% vs 9%). Ideally, BRCA1/2 testing should be based on both approaches to identify all patients with mPC eligible for PARP inhibitor therapy. PATIENT SUMMARY: Our study shows that genetic tests for both tumor tissue and blood samples results in higher rates of detection of BRCA1/2 gene alterations in patients with metastatic prostate cancer.

Full functional-length urethral sphincter- and neurovascular bundle preservation improves long-term continence rates after robotic-assisted radical prostatectomy.

The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (≥ 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1-2, 4% 3-5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51-27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%.

External Tertiary-Care-Hospital Validation of the Epidemiological SEER-Based Nomogram Predicting Downgrading in High-Risk Prostate Cancer Patients Treated with Radical Prostatectomy.

We aimed to externally validate the SEER-based nomogram used to predict downgrading in biopsied high-risk prostate cancer patients treated with radical prostatectomy (RP) in a contemporary European tertiary-care-hospital cohort. We relied on an institutional tertiary-care database to identify biopsied high-risk prostate cancer patients in the National Comprehensive Cancer Network (NCCN) who underwent RP between January 2014 and December 2022. The model's downgrading performance was evaluated using accuracy and calibration. The net benefit of the nomogram was tested with decision-curve analyses. Overall, 241 biopsied high-risk prostate cancer patients were identified. In total, 51% were downgraded at RP. Moreover, of the 99 patients with a biopsy Gleason pattern of 5, 43% were significantly downgraded to RP Gleason pattern ≤ 4 + 4. The nomogram predicted the downgrading with 72% accuracy. A high level of agreement between the predicted and observed downgrading rates was observed. In the prediction of significant downgrading from a biopsy Gleason pattern of 5 to a RP Gleason pattern ≤ 4 + 4, the accuracy was 71%. Deviations from the ideal predictions were noted for predicted probabilities between 30% and 50%, where the nomogram overestimated the observed rate of significant downgrading. This external validation of the SEER-based nomogram confirmed its ability to predict the downgrading of biopsy high-risk prostate cancer patients and its accurate use for patient counseling in high-volume RP centers.

Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer.

BACKGROUND: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). METHODS: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. RESULTS: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). CONCLUSION: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.

Feasibility and outcome of radical prostatectomy following inductive neoadjuvant therapy in patients with suspicion of rectal infiltration.

OBJECTIVE: To determine the feasibility and outcome of radical prostatectomy (RP) following neoadjuvant therapy (NAT) in patients with initial inoperable, rectum-infiltrating cT4 prostate cancer (PCa). METHODS: From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating PCa at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database. Two patients were still inoperable after NAT. Downsizing was administered for at least 20 weeks and RP was performed after excluding ongoing rectal infiltration. RESULTS: At diagnosis, median PSA was 42.5 ng/ml (IQR: 23.0-66.1). Inductive NAT consisted of androgen deprivation therapy (ADT) in combination with chemotherapy (n = 9) or without chemotherapy (n = 14). Median preoperative PSA was 0.93 ng/ml (IQR: 0.24-0.40). Median time from NAT to RP was 6 months (IQR: 5-7). Two patients were still inoperable after NAT. Of 24 patients undergoing RP, abortion of surgery due to inoperability was observed in 2 patients (8.4%), demonstrating a total failure rate of NAT in 4 out of 26 patients (15.4%). One patient suffered a rectal injury with consecutive colostomy (4.2%). No Clavien-Dindo complication Grade IV or V were observed. Urinary continence was achieved in 16 patients (84.2%). Sufficient erection for sexual intercourse was present in 2 patients (10.5%). All patients received adjuvant ADT with or without radiation therapy. Median PSA at 13 months was 0.08 ng/ml (IQR: 0.01-0.74). CONCLUSION: RP of initially rectum infiltrating PCa is feasible and safe after inductive NAT, however complications rates tend to be higher compared to standard RP.

Diabetes mellitus lowers the chance of short-term urinary continence recovery in prostate cancer patients undergoing radical prostatectomy.

Introduction: The aim of this article was to test the impact of diabetes mellitus (DM) on short-term urinary continence in patients undergoing radical prostatectomy (RP). Material and methods: We relied on an institutional tertiary-care database to identify patients who underwent RP between 11/2018 and 02/2021 with data available on short-term urinary continence status (30-90 days post-surgery). Continence was defined as the usage of no or one safety-pad within 24 hours. Univariable and multivariable logistic regression models tested the correlation between DM and short-term continence. Covariates consisted of pathological T-stage, body mass index, prostate volume, surgical approach and nerve-sparing. Results: Of 142 eligible patients, 15 (11%) patients exhibited concomitant DM. Patients diagnosed with DM exhibited lower continence rates at short-term follow-up compared to patients without DM (33 vs 63%, p = 0.03). In univariable and multivariable logistic regression models, DM was strongly associated with reduced chances of short-term urinary continence recovery (multivariable odds ratio [OR]: 0.26, 95%-CI: 0.07-0.86; p = 0.03). Furthermore, pathological T-stage (pT3/pT4) was additionally associated with reduced chance of urinary continence in logistic regression models (multivariable OR: 0.43, 95%-CI: 0.19-0.94; p = 0.04). Other covariables failed to reach statistical significance in multivariable logistic regression analyses predicting urinary continence. Conclusions: DM was associated with lower chances of short-term urinary continence recovery in a contemporary cohort of patients undergoing radical prostatectomy. Patients with DM should be preoperatively informed and intensified, postoperative pelvic floor training should be considered in this subgroup of RP patients.

Performance of Combined Magnetic Resonance Imaging/Ultrasound Fusion-guided and Systematic Biopsy of the Prostate in Biopsy-naïve Patients and Patients with Prior Biopsies.

BACKGROUND: As recent prospective studies showed targeted biopsies (TBs) to be superior to systematic biopsies (SBs), magnetic resonance imaging (MRI) is gaining wider acceptance in the diagnostic setup of prostate cancer (PCa). OBJECTIVE: To examine the performance of MRI/ultrasound fusion-guided TB in combination with SB in the detection of PCa in patients with and without prior biopsy. DESIGN, SETTING, AND PARTICIPANTS: A total of 219 men undergoing combined transrectal TB and 12-core SB from February 2014 to November 2018 were analysed. For all patients showing a suspicion of PCa in multiparametric MRI, TB was performed using fusion imaging with real-time virtual sonography. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer detection rates (CDRs) and significant CDRs for TB, SB, and TB+SB were analysed. Further stratification was performed for a number of previous biopsy sessions and Prostate Imaging Reporting and Data System (PI-RADS) score. Significant PCa was defined as any PCa with Gleason score ≥3+4. RESULTS AND LIMITATIONS: Of all, 141 patients were biopsy naïve, while 78 patients had at least one prior biopsy. Median prostate-specific antigen (PSA) level prior to biopsy was 8.4ng/ml (interquartile range 5.5-11.8ng/ml). The overall CDR was 63.5% (139/219), while the PI-RADS-dependent CDRs for the combination of TB+SB were 29.1%, 67.7%, and 86.2% for patients with PI-RADS 3, 4, and 5, respectively. Looking at TB or SB alone, CDRs were 55.7% and 57.5%. The overall CDR for significant PCa was 51.6%. (18.2%, 50.5%, and 81.5% for PI-RADS 3, 4, and 5, respectively). CDRs were significantly higher for biopsy-naïve patients (65.2% vs 67.4% vs 71.6% for TB vs SB vs TB+SB) than for patients with one previous negative biopsy (38.2% vs 43.6% vs 50.9% for TB vs SB vs TB+SB; all p<0.01). CONCLUSIONS: Multiparametric MRI can raise the CDR in patients with and without biopsies performed earlier. With higher PI-RADS lesions, the risk of harbouring PCa increases. Combining TB with SB further improved the diagnostic accuracy in biopsy-naïve patients and after one previous negative biopsy. PATIENT SUMMARY: Multiparametric magnetic resonance imaging before prostate biopsy increases cancer detection rates in biopsy-naïve patients and patients with a previous negative biopsy. The combination of targeted biopsy with systematic biopsy improved the diagnostic accuracy in biopsy-naïve patients and after one previous negative biopsy.

Influence of Biopsy Gleason Score on the Risk of Lymph Node Invasion in Patients With Intermediate-Risk Prostate Cancer Undergoing Radical Prostatectomy.

Objective: To analyze the influence of biopsy Gleason score on the risk for lymph node invasion (LNI) during pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy (RP) for intermediate-risk prostate cancer (PCa). Materials and Methods: We retrospectively analyzed 684 patients, who underwent RP between 2014 and June 2020 due to PCa. Univariable and multivariable logistic regression, as well as binary regression tree models were used to assess the risk of positive LNI and evaluate the need of PLND in men with intermediate-risk PCa. Results: Of the 672 eligible patients with RP, 80 (11.9%) men harbored low-risk, 32 (4.8%) intermediate-risk with international society of urologic pathologists grade (ISUP) 1 (IR-ISUP1), 215 (32.0%) intermediate-risk with ISUP 2 (IR-ISUP2), 99 (14.7%) intermediate-risk with ISUP 3 (IR-ISUP3), and 246 (36.6%) high-risk PCa. Proportions of LNI were 0, 3.1, 3.7, 5.1, and 24.0% for low-risk, IR-ISUP1, IR-ISUP 2, IR-ISUP-3, and high-risk PCa, respectively (p < 0.001). In multivariable analyses, after adjustment for patient and surgical characteristics, IR-ISUP1 [hazard ratio (HR) 0.10, p = 0.03], IR-ISUP2 (HR 0.09, p < 0.001), and IR-ISUP3 (HR 0.18, p < 0.001) were independent predictors for lower risk of LNI, compared with men with high-risk PCa disease. Conclusions: The international society of urologic pathologists grade significantly influence the risk of LNI in patients with intermediate- risk PCa. The risk of LNI only exceeds 5% in men with IR-ISUP3 PCa. In consequence, the need for PLND in selected patients with IR-ISUP 1 or IR-ISUP2 PCa should be critically discussed.

Inverse Stage Migration in Radical Prostatectomy-A Sustaining Phenomenon.

Objective: To investigate temporal trends in prostate cancer (PCa) radical prostatectomy (RP) candidates. Materials and Methods: Patients who underwent RP for PCa between January 2014 and December 2019 were identified form our institutional database. Trend analysis and logistic regression models assessed RP trends after stratification of PCa patients according to D'Amico classification and Gleason score. Patients with neoadjuvant androgen deprivation or radiotherapy prior to RP were excluded from the analysis. Results: Overall, 528 PCa patients that underwent RP were identified. Temporal trend analysis revealed a significant decrease in low-risk PCa patients from 17 to 9% (EAPC: -14.6%, p < 0.05) and GS6 PCa patients from 30 to 14% (EAPC: -17.6%, p < 0.01). This remained significant even after multivariable adjustment [low-risk PCa: (OR): 0.85, p < 0.05 and GS6 PCa: (OR): 0.79, p < 0.001]. Furthermore, a trend toward a higher proportion of intermediate-risk PCa undergoing RP was recorded. Conclusion: Our results confirm that inverse stage migration represents an ongoing phenomenon in a contemporary RP cohort in a European tertiary care PCa center. Our results demonstrate a significant decrease in the proportion of low-risk and GS6 PCa undergoing RP and a trend toward a higher proportion of intermediate-risk PCa patients undergoing RP. This indicates a more precise patient selection when it comes to selecting suitable candidates for definite surgical treatment with RP.

Comparison of Complication Rates with Antibiotic Prophylaxis with Cefpodoxime Versus Fluoroquinolones After Transrectal Prostate Biopsy.

BACKGROUND: After recommended restriction of the use of fluoroquinolones, the optimal antibiotic prophylaxis for transrectal prostate biopsy is still under debate. OBJECTIVE: To test the effectiveness of cefpodoxime as oral antibiotic prophylaxis for transrectal prostate biopsies and the complication rates relative to fluoroquinolones. DESIGN, SETTING, AND PARTICIPANTS: Antibiotic prophylaxis for transrectal prostate biopsies at the Department of Urology at University Hospital Frankfurt was fluoroquinolones for 342 consecutive patients in January 2018 and December 2019 and cefpodoxime for 100 patients from January 2020 to July 2020. Data were prospectively evaluated and retrospectively analyzed. Patients were followed up according to clinical routine at 6 wk after biopsy at the earliest. Patients without follow-up (n = 98) and those receiving antibiotic prophylaxis other than cefpodoxime or fluoroquinolones (n = 15) were excluded. INTERVENTION: Use of cefpodoxime or fluoroquinolones as antibiotic prophylaxis for transrectal prostate biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were used to predict biopsy-related complications according to antibiotic prophylaxis. RESULTS AND LIMITATIONS: Of 442 patients, 100 (22.6%) received cefpodoxime as antibiotic prophylaxis. Patient baseline and biopsy characteristics were comparable between the cefpodoxime and fluoroquinolone groups. Moreover, there were no differences in the number of prior prostate biopsies or the proportions of systematic vs. fusion biopsies (p > 0.05). There were no differences between the groups in infectious complications such as epididymitis and prostatitis after biopsy. Infectious complication rates were very low, at 2.0% in the cefpodoxime and0.9%fluoroquinolone group. Moreover, there were no differences between the groups in patient-reported complications, such as gross hematuria occurring at more than 5 d after biopsy, hematospermia, or rectal bleeding. In multivariable analyses, after adjustment for patient and prostate biopsy characteristics, cefpodoxime was not associated with higher complication rates than fluoroquinolones (p > 0.05). CONCLUSIONS: Complications after transrectal prostate biopsies are rare and cefpodoxime might be a sufficient choice as oral antibiotic prophylaxis and noninferior compared to fluoroquinolones. PATIENT SUMMARY: Cefpodoxime might be a sufficient choice as an easily applicable oral antibiotic prophylaxis for transrectal prostate biopsy. The safety profile of cefpodoxime is comparable to the safety profile of fluoroquinolones.

Influence of Tumor Burden on Serum Prostate-Specific Antigen in Prostate Cancer Patients Undergoing Radical Prostatectomy.

OBJECTIVE: We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP. PATIENTS AND METHODS: From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics. RESULTS: Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41-10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26-46) and median tumor weight was 3.7 g (IQR: 1.8-7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15-0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight. CONCLUSION: Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.

Immunohistochemistry for Prostate Biopsy-Impact on Histological Prostate Cancer Diagnoses and Clinical Decision Making.

BACKGROUND: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making. METHODS: Between January 2017-June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy. RESULTS: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy (p < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7-10. CONCLUSIONS: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.