Long-Term Follow-Up in Patients Undergoing Renal Mass Biopsy: Seeding is not Anecdotal.

INTRODUCTION: Renal biopsy is recommended if the outcome might alter therapeutic decisions for patients who present with renal masses of unclear etiology. However, little is known about long-term risks related to this procedure. PATIENTS AND METHODS: We performed a retrospective analysis of an institutional database maintained by a tertiary referral center that included patients who underwent renal biopsies between 2003 and 2005 with a follow-up of at least 15 years. Renal biopsies were taken percutaneously with a coaxial technique according to guideline recommendations and included off-line ultrasound guidance. RESULTS: We identified 106 patients who underwent biopsies for a renal mass of unclear etiology. The median age was 58.7 years (43.7-66.2). A median of 4.2 (3-6) biopsies were collected from each patient. Tumor seeding leading to local growth was identified in 6 patients (5,7%) after a median follow-up of 8.2 years. Four of these lesions that were resected exhibited the same histology as the original biopsy result; these patients experienced no further recurrence. In 45 patients (42%), the biopsy results led to a therapy other than surgery (n = 28 lymphoma, n = 6 metastasis from other malignancies, n = 11 oncocytoma). The remaining 61 patients (58%) were diagnosed with renal cell carcinoma treated either surgically or with ablation. None of the patients developed metastatic spread related to tumor seeding. CONCLUSION: Tumor seeding after renal mass biopsy is a rare, but relevant risk associated with this procedure. As indications for renal mass biopsy increase, longer-term follow-up and improved biopsy techniques should be considered to address this complication.

Long-term Prostate Cancer-specific Mortality After Prostatectomy, Brachytherapy, External Beam Radiation Therapy, Hormonal Therapy, or Monitoring for Localized Prostate Cancer.

BACKGROUND: The optimal treatment of localized prostate cancer (PCa) remains controversial. OBJECTIVE: To compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa. DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1-3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram. RESULTS AND LIMITATIONS: Among 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8-13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24-1.98; p < 0.001) for BT, 1.55 (95% CI 1.26-1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94-2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30-2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient. CONCLUSIONS: In a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited. PATIENT SUMMARY: We evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring.

Current perceptions and working time models of female urologists in Germany: results of a large-scale survey.

PURPOSE: Female urologists are distinctly underrepresented in leading positions. The reasons behind this inequity remain unclear, with some suggesting factors such as family responsibilities, part-time work and insufficient mentorship. This study aimed to explore and characterize the working conditions of female urologists in Germany, with a focus on factors influencing the working time model. METHODS: A questionnaire was developed and distributed to 1343 female members of the German Society of Urology between February and March 2022. The survey consisted of 43 questions covering the categories demographics, occupation situation, satisfaction at work, family situation, career aspects and research activity. RESULTS: Of the 487 female German urologists who participated in the survey, 167 (34.3%) worked part-time. Doctors in training were significantly less likely to work part-time than colleagues who had completed their specialist training (p < 0.001). Only 10% of female doctors in training reported working part-time. Similarly, having children (p < 0.001) and engaging in scientific activities (p = 0.03) were independent factors influencing part-time work, with children increasing the likelihood of working part-time as expected, while scientifically active female urologists were more likely to work full-time. CONCLUSION: This study provides the largest survey on the situation of female urologists in German-speaking countries to date. Part-time work during specialist training is rare, while more than 50% of female urologists with children work part-time. With the projected decline in the number of practicing physicians and the increasing demand for medical attention, it is crucial to find ways to retain and support healthcare professionals, particularly female urologists.

[Factors influencing job satisfaction of female urologists-results of a survey by the German Society of Urology (DGU)]. / Einflussfaktoren für die Berufszufriedenheit von Urologinnen ­ Ergebnisse einer Befragung der Deutschen Gesellschaft für Urologie e. V. (DGU).

INTRODUCTION: Job satisfaction is a valuable good. However, literature on job satisfaction of female and male physicians, especially in the field of urology, is scarce. Therefore, the aim of this study was to evaluate job satisfaction among female members of the German Society of Urology (DGU). MATERIALS AND METHODS: An online questionnaire was sent to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 female physicians were statistically analyzed regarding baseline characteristics and in relation to job satisfaction and satisfaction with the choice of specialty. RESULTS: The median age of the participants was 37 (IQR 33; 45) years. While 91% of the respondents were rather or very satisfied with their choice of specialty-urology-only about 54% of the female urologists were satisfied with their job situation. Of the female urologists satisfied (vs. not satisfied) with their professional situation, 95% (vs. 87%) were also satisfied with their choice of urology as their specialty. Satisfaction with the working time model (odds ratio [OR] 9.61) and feeling unequal treatment (OR: 0.18) were independent predictors of satisfaction with the professional situation. CONCLUSION: Considering the increasing proportion of women in the health sector, it is important to identify factors influencing decisions on career and choice of specialty as well as career progression. Achieving career goals, increasing satisfaction with the working time model, and reducing unequal treatment or discrimination are central arguments for sustainably increasing the job satisfaction of female urologists.

Explainable ML models for a deeper insight on treatment decision for localized prostate cancer.

Although there are several decision aids for the treatment of localized prostate cancer (PCa), there are limitations in the consistency and certainty of the information provided. We aimed to better understand the treatment decision process and develop a decision-predicting model considering oncologic, demographic, socioeconomic, and geographic factors. Men newly diagnosed with localized PCa between 2010 and 2015 from the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database were included (n = 255,837). We designed two prediction models: (1) Active surveillance/watchful waiting (AS/WW), radical prostatectomy (RP), and radiation therapy (RT) decision prediction in the entire cohort. (2) Prediction of AS/WW decisions in the low-risk cohort. The discrimination of the model was evaluated using the multiclass area under the curve (AUC). A plausible Shapley additive explanations value was used to explain the model's prediction results. Oncological variables affected the RP decisions most, whereas RT was highly affected by geographic factors. The dependence plot depicted the feature interactions in reaching a treatment decision. The decision predicting model achieved an overall multiclass AUC of 0.77, whereas 0.74 was confirmed for the low-risk model. Using a large population-based real-world database, we unraveled the complex decision-making process and visualized nonlinear feature interactions in localized PCa.

Characterization of Human Papilloma Virus in Prostate Cancer Patients Undergoing Radical Prostatectomy-A Prospective Study of 140 Patients.

INTRODUCTION: The association between human papilloma virus (HPV) and the pathogenesis of prostate cancer (PCa) is still controversial. Existing studies often lack information about clinical risk factors, are limited by their retrospective design or only use a single detection method for HPV. MATERIAL AND METHODS: A total of 140 patients undergoing radical prostatectomy (RP) for PCa at the Department of Urology, Ludwig Maximilian University of Munich, Germany, were prospectively enrolled. Knowledge of HPV and sociodemographic parameters were assessed with questionnaires. The following methods were used for HPV detection: RP specimens were tested for HPV DNA by PCR. If HPV DNA was detected, an LCD-Array hybridization technique was used for HPV subtyping, and immunohistochemical staining for p16 was performed as a surrogate marker for HPV infection. Serological titers of HPV-16 L1 antibodies were measured using an HPV-16-specific immunoassay. RESULTS: HPV DNA was detected in 9.3% (13/140) of RP specimens, with HPV-16 being the most predominantly detected subtype (5/13 = 39%). HPV-16 L1 antibody levels were below the limit of detection in 98% of patients (137/140). We found no significant difference between HPV PCR-positive (HPV+) and -negative (HPV-) patients in terms of HPV-16 antibody levels, history of HPV-associated diseases, level of education or marital status. Seventy-five percent of all PCa patients had never heard of HPV before. An acinar adenocarcinoma of the prostate was the most frequently detected histologic type in both HPV+ (100%) and HPV- (98%) patients (p = 0.86). HPV+ patients had fewer positive biopsy cores (3.5 vs. 5.8; p = 0.01) and a lower maximal tumor infiltration rate per core (37% vs. 57%; p = 0.03) compared to HPV- patients. However, when analyzing the whole prostate and the lymph nodes after RP, there were no significant differences in TNM stage, Gleason score or tumor volume between both groups. In a subgroup analysis of all high-risk HPV patients (n = 6), we found no significant differences in sociodemographic, clinical or histopathological parameters compared to HPV- or low-risk HPV+ patients. CONCLUSION: In our prospective study, we were not able to prove a clinically significant impact of HPV status on tumor characteristics in RP specimens. Most men with PCa had never heard of HPV, despite its proven causal association with other tumor entities.

Observation, Radiotherapy, or Radical Prostatectomy for Localized Prostate Cancer: Survival Analysis in the United States.

PURPOSE: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010-2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50-79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D'Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. RESULTS: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81-0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41-0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. CONCLUSIONS: Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation-especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group.

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer poses a therapeutic challenge with poor prognosis. The VISION trial showed prolonged progression-free and overall survival in patients treated with lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) radioligand therapy compared with using the standard of care (SoC) alone. The objective of this study was to determine the cost-effectiveness of 177Lu-PSMA-617 treatment compared with SoC therapy. METHODS: A partitioned survival model was developed using data from the VISION trial, which included overall and progression-free survival and treatment regimens for 177Lu-PSMA-617 and SoC. Treatment costs, utilities for health states, and adverse events were derived from public databases and the literature. Because 177Lu-PSMA-617 was only recently approved, costs for treatment were extrapolated from 177Lu-DOTATATE. Outcome measurements included the incremental cost, effectiveness, and cost-effectiveness ratio. The analysis was performed in a US setting from a healthcare system perspective over the lifetime horizon of 60 months. The willingness-to-pay threshold was set to $50,000, $100,000, and $200,000 per quality-adjusted life years (QALYs). RESULTS: The 177Lu-PSMA-617 group was estimated to gain 0.42 incremental QALYs. Treatment using 177Lu-PSMA-617 led to an increase in costs compared with SoC ($169,110 vs $85,398). The incremental cost, effectiveness, and cost-effectiveness ratio for 177Lu-PSMA-617 therapy was $200,708/QALYs. Sensitivity analysis showed robustness of the model regarding various parameters, which remained cost-effective at all lower and upper parameter bounds. In probabilistic sensitivity analysis using Monte Carlo simulation with 10,000 iterations, therapy using 177Lu-PSMA-617 was determined as the cost-effective strategy in 37.14% of all iterations at a willingness-to-pay threshold of $200,000/QALYs. CONCLUSIONS: Treatment using 177Lu-PSMA-617 was estimated to add a notable clinical benefit over SoC alone. Based on the model results, radioligand therapy represents a treatment strategy for patients with metastatic castration-resistant prostate cancer with cost-effectiveness in certain scenarios.

Technical Outcome, Clinical Success, and Complications of Low-Milliampere Computed Tomography Fluoroscopy-Guided Drainage of Lymphoceles Following Radical Prostatectomy with Pelvic Lymph Node Dissection.

To evaluate the technical outcome, clinical success, and safety of low-milliampere CT fluoroscopy (CTF)-guided percutaneous drain (PD) placement in patients with lymphoceles following radical prostatectomy (RP) with pelvic lymph node dissection (LND). This retrospective analysis comprised 65 patients with PD placement in lymphoceles following RP under low-milliampere CTF guidance. Technical and clinical success were evaluated. Complications within a 30-day time interval associated with CTF-guided PD placement were classified according to SIR. Patient radiation exposure was quantified using dose-length products (DLP) of the pre-interventional planning CT scan (DLPpre), of the sum of intra-interventional CT fluoroscopic acquisitions (DLPintra) and of the post-interventional control CT scan (DLPpost). Eighty-nine lymphoceles were detected. Seventy-seven CT-guided interventions were performed, with a total of 92 inserted drains. CTF-guided lymphocele drainage was technically successful in 100% of cases. For all symptomatic patients, improvement in symptoms was reported within 48 h after intervention. Time course of C-reactive protein and Leucocytes within 30 days revealed a statistically significant (p < 0.0001) decrease. Median DLPpre, DLPintra and DLPpost were 431 mGy*cm, 45 mGy*cm and 303 mGy*cm, respectively. Only one minor complication (self-resolving haematoma over the bladder dome; SIR Grade 2) was observed. Low-milliampere CTF-guided drainage is a safe treatment option in patients with lymphoceles following RP with pelvic LND characterized by high technical and good clinical success rates, which provides rapid symptom relief and serves as definite treatment or as a bridging therapy prior to laparoscopic marsupialisation.

[Promoting women in urology using the example of habilitation]. / Frauenförderung in der Urologie am Beispiel der Habilitation.

BACKGROUND: The proportion of female urologists is steadily increasing, yet they continue to be underrepresented in academic leadership positions. A postdoctoral lecture qualification (habilitation), which is mandatory for a successful scientific career, is achieved significantly less often by female urologists in Germany than by their male colleagues. OBJECTIVE: To identify factors to effectively promote female urologists into academic leadership positions, the current situation, as well as factors influencing successful habilitation of women who are members of the German Society of Urology (Deutsche Gesellschaft für Urologie [DGU]) were investigated. METHODS: An online questionnaire was distributed to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 women were statistically analyzed with respect to baseline characteristics and in relation to research funding. The primary endpoint of our study was the habilitation rate. RESULTS: The average age of the 521 participating female urologists who completed the questionnaire was 37 years (range 21-67 years). Of these, most female physicians were in postgraduate training (n = 168, 32%), worked full-time (n = 324, 62%), and had children (n = 277, 53%). Overall, 359 (69%) of the participants had a PhD and 63 (12%) were still working on their PhD. Thirty (5.8%) female urologists had a habilitation. In univariable logistic regression models, age (odds ratio [OR] 1.06), working time model (part-time OR 0.19), a research fellowship (OR 21.4), release from clinical work for research purposes (OR 13.7), and participation in a funding program (OR 6.9) or mentoring program (OR 7.0) were independent predictors of achieving habilitation. Whether a urologist had children was not an independent predictor of achieving habilitation. In multivariable logistic regression models, age (OR 1.08), and a research fellowship (OR 9.04) were independent predictors of achieving habilitation. CONCLUSIONS: Promoting habilitation among female urologists is required in order to increase the proportion of women in leading academic positions. The results of the data analysis show that the promotion of research fellowships explicitly for women could be a promising approach.

Total Tumor Volume on 18F-PSMA-1007 PET as Additional Imaging Biomarker in mCRPC Patients Undergoing PSMA-Targeted Alpha Therapy with 225Ac-PSMA-I&T.

Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, <10 months OS) and long-term survivors (LTS, ≥10 months OS), TTV and PSA were comparable (p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions.

RAS-NOTECHS: validity and reliability of a tool for measuring non-technical skills in robotic-assisted surgery settings.

BACKGROUND: Non-technical skills (NTS) are essential for safe surgical practice as they impact workflow and patient outcomes. Observational tools to measure operating room (OR) teams' NTS have been introduced. However, there are none that account for the specific teamwork challenges introduced by robotic-assisted surgery (RAS). We set out to develop and content-validate a tool to assess multidisciplinary NTS in RAS. METHODOLOGY: Stepwise, multi-method procedure. Observations in different surgical departments and a scoping literature review were first used to compile a set of RAS-specific teamwork behaviours. This list was refined and expert validated using a Delphi consensus approach consisting of qualitative interviews and a quantitative survey. Then, RAS-specific behaviours were merged with a well-established assessment tool on OR teamwork (NOTECHS II). Finally, the new tool-RAS-NOTECHS-was applied in standardized observations of real-world procedures to test its reliability (inter-rater agreement via intra-class correlations). RESULTS: Our scoping review revealed 5242 articles, of which 21 were included based on pre-established inclusion criteria. We elicited 16 RAS-specific behaviours from the literature base. These were synthesized with further 18 behavioural markers (obtained from 12 OR-observations) into a list of 26 behavioural markers. This list was reviewed by seven RAS experts and condensed to 15 expert-validated RAS-specific behavioural markers which were then merged into NOTECHS II. For five observations of urologic RAS procedures (duration: 13 h and 41 min), inter-rater agreement for identification of behavioural markers was strong. Agreement of RAS-NOTECHS scores indicated moderate to strong agreement. CONCLUSIONS: RAS-NOTECHS is the first observational tool for multidisciplinary NTS in RAS. In preliminary application, it has been shown to be reliable. Since RAS is rapidly increasing and challenges for effective and safe teamwork remain at the forefront of quality and safety of surgical care, RAS-NOTECHS may contribute to training and improvement efforts in technology-facilitated surgeries.

Active surveillance in intermediate-risk prostate cancer with PSA 10-20 ng/mL: pathological outcome analysis of a population-level database.

BACKGROUND: Active surveillance (AS) is generally recognized as the preferred option for men with low-risk prostate cancer. Current guidelines use prostate-specific antigen (PSA) of 10-20 ng/mL or low-volume biopsy Gleason grade group (GG) 2 as features that, in part, define the favorable intermediate-risk disease and suggest that AS may be considered for some men in this risk category. METHODS: We identified 26,548 men initially managed with AS aged <80 years, with clinically localized prostate cancer (cT1-2cN0M0), PSA ≤ 20 ng/mL, biopsy GG ≤ 2 with percent positive cores ≤33% and who converted to treatment with radical prostatectomy from the surveillance, epidemiology, and end results prostate with the watchful waiting database. Multivariable logistic regression was performed to determine predictors of adverse pathology at RP according to PSA level (<10 vs 10-20 ng/mL) and GG (1 vs 2). RESULTS: Of 1731 men with GG 1 disease and PSA 10-20 ng/mL, 382 (22.1%) harbored adverse pathology compared to 2340 (28%) of 8,367 men with GG 2 and a PSA < 10 ng/mL who had adverse pathology at RP. On multivariable analysis, the odds of harboring adverse pathology with a PSA 10-20 ng/mL (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.71-2.05, p < 0.001) was less than that of GG 2 (OR 2.56, 95%CI 2.40-2.73, p < 0.001) after adjustment. CONCLUSIONS: Our results support extending AS criteria more permissively to carefully selected men with PSA 10-20 ng/mL and GG 1 disease.

Feasibility of Different Tumor Delineation Approaches for 18F-PSMA-1007 PET/CT Imaging in Prostate Cancer Patients.

BACKGROUND: Delineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68Ga-labeled ligands; nonetheless, 18F-labeled PET ligands are gaining increasing importance due to advantages over 68Ga-labeled compounds. However, standardized tumor delineation methods for 18F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18F-PSMA-1007 PET. METHODS: Fifty patients with metastatic prostate cancer, 18F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to III) liver (SUVliver), IV) parotis (SUVparotis) and V) spleen (SUVspleen). RESULTS: A fixed SUV of 4.0 (r=0.807, r2 = 0.651, p<0.001) showed the best overall association with the volumetric reference. 55% SUVmax (r=0.627, r2 = 0.393, p<0.001) showed highest association using an isocontour-based threshold. Best background-based approaches were 60% SUVliver (r=0.715, r2 = 0.511, p<0.001), 80% SUVparotis (r=0.762, r2 = 0.581, p<0.001) and 60% SUVspleen (r=0.645, r2 = 0.416, p<0.001). Background tissues SUVliver, SUVparotis & SUVspleen did not correlate (p>0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUVmax, 42% SUVmax and 20% SUVmax) revealed inferior association for LNM delineation. CONCLUSIONS: A threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated.

Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer.

18F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus 18F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1-4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. PATIENT SUMMARY: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.

How Often Does Magnetic Resonance Imaging Detect Prostate Cancer Missed by Transrectal Ultrasound?

BACKGROUND: Lesion-targeted prostate biopsy based on multiparametric magnetic resonance imaging (mpMRI) has been shown to be superior to systematic transrectal ultrasound (TRUS) biopsy (SBx) alone in men at risk for prostate cancer (PCa). However, the incremental benefit of MRI-targeted biopsy (MBx) beyond SBx with ultrasound-targeted biopsy (UBx) is less clear. OBJECTIVE: We performed a three-way comparison of UBx versus MBx versus SBx for PCa detection. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center cohort study was conducted on consecutive patients with PCa suspicion or low-risk PCa on active surveillance (AS). All men had at least one lesion (Prostate Imaging Reporting and Data System [PI-RADS] ≥3) on pre-biopsy mpMRI. UBx, MBx, and SBx were performed during the same encounter, and the urologists were blinded to MRI results and targeting until both SBx and UBx were completed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The ability of each biopsy type to identify the highest grade group (GG) was determined, and UBx and MBx were compared using a paired t test. RESULTS AND LIMITATIONS: We prospectively enrolled 201 consecutive men undergoing targeted prostate biopsy: 72 (36%) were biopsy-naïve, 34 (17%) had a prior negative SBx, and 95 (47%) were on AS. Median age and prostate-specific antigen were 66 yr (interquartile range [IQR] 62-71) and 6.8 ng/ml (IQR 4.9-9.8), respectively. Suspicious hypoechoic lesions were reported on TRUS in 69%. Among the 169 men with PCa, SBx detected the highest GG or was equivalent to UBx/MBx in 136 (80%) men. UBx detected the highest GG or was equivalent to MBx in 19 (11%) men, and MBx alone detected the highest GG in 14 (8%) men. There was no significant difference between UBx and MBx in direct comparison (p = 0.08). Limitations include that patients were not randomized, our population was heterogeneous, and TRUS expertise at a tertiary care academic center might not reflect routine practice. CONCLUSIONS: In the setting of high expertise and experience with both ultrasound and MRI, MBx offers only a modest benefit over SBx and UBx. PATIENT SUMMARY: At a highly experienced academic medical center, we examined the detection rates of prostate cancer among men undergoing prostate biopsy using three techniques: transrectal ultrasound lesion-targeted biopsy, magnetic resonance imaging-targeted biopsy, and systematic biopsy. We identified a few more cases of aggressive prostate cancer with magnetic resonance imaging-targeted biopsy, but a large majority was found by ultrasound alone.

Influence of pelvic lymph node dissection and node-positive disease on biochemical recurrence, secondary treatment, and survival after radical prostatectomy in men with prostate cancer.

BACKGROUND: The benefit of pelvic lymph node dissection (PLND) at radical prostatectomy (RP) remains unclear given the low prevalence of known nodal disease (pN1) and concerns about its therapeutic utility. OBJECTIVE: To characterize the impact of PLND and secondary treatment on oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of men who underwent primary RP with PLND for prostate cancer (PCa) at our institution since 2003. Men stratified by nodal status. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Outcomes include biochemical recurrence-free survival (bRFS), overall survival, and PCa-specific mortality (PCSM). Multivariable Cox regression models used for each outcome. RESULTS AND LIMITATIONS: Of 1,543 men who underwent primary RP, 174 (11%) had pN1 disease. Median follow-up was 34 months (interquartile range, 15-62). Seven-year outcomes were similar whether less than or ≥14 LNs dissected. Among node-positive patients, 29% had undetectable (UDT) prostate-specific antigen (PSA), 11% had UDT PSA + adjuvant therapy, and 60% had detectable PSA, and 7-year bRFS differed (75% for UDT PSA, 90% for UDT + adjuvant therapy, 38% for detectable PSA, p < .01). Survival outcomes did not differ. In multivariable analysis, detectable PSA (vs. UDT, HR 5.2, 95% CI 2.0-13.3) associated with worse bRFS. After salvage treatment, 7-year outcomes did not differ between groups. Study limited by retrospective review.