Development and external validation of a multivariable [68Ga]Ga-PSMA-11 PET-based prediction model for lymph node involvement in men with intermediate or high-risk prostate cancer.

PURPOSE: To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [68Ga]Ga-PSMA-11 PET. METHODS: A consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [68Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). RESULTS: A combined model including prostate-specific antigen, biopsy Gleason grade group, [68Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [68Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of ≥ 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA. CONCLUSIONS: Our results indicate that information from [68Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.

Safety and efficiency of repeat salvage lymph node dissection for recurrence of prostate cancer using PSMA-radioguided surgery (RGS) after prior salvage lymph node dissection with or without initial RGS support.

BACKGROUND AND OBJECTIVE: Metastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND). MATERIALS AND METHODS: We identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan-Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery. RESULTS AND LIMITATIONS: Complete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3-22). On multivariable regression, only age (HR 1.09, 95% CI 1.01-1.17) and preoperative PSA (HR 1.23, 95% CI 1.01-1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99-1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien-Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size. CONCLUSION: In this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery.

Hospital rating websites play a minor role for uro-oncologic patients when choosing a hospital for major surgery: results of the German multicenter NAVIGATOR-study.

PURPOSE: Hospital rating websites (HRW) offer decision support in hospital choice for patients. To investigate the impact of HRWs of uro-oncological patients undergoing elective surgery in Germany. METHODS: From 01/2020 to 04/2021, patients admitted for radical prostatectomy, radical cystectomy, or renal tumor surgery received a questionnaire on decision-making in hospital choice and the use of HRWs at 10 German urologic clinics. RESULTS: Our study includes n = 812 completed questionnaires (response rate 81.2%). The mean age was 65.2 ± 10.2 years; 16.5% were women. Patients were scheduled for prostatectomy in 49.1%, renal tumor surgery in 20.3%, and cystectomy in 13.5% (other 17.1%). Following sources of information influenced the decision process of hospital choice: urologists' recommendation (52.6%), previous experience in the hospital (20.3%), recommendations from social environment (17.6%), the hospital's website (10.8%) and 8.2% used other sources. Only 4.3% (n = 35) used a HRW for decision making. However, 29% changed their hospital choice due to the information provided HRW. The most frequently used platforms were Weisse-Liste.de (32%), the AOK-Krankenhausnavigator (13%) and Qualitaetskliniken.de (8%). On average, patients rated positively concerning satisfaction with the respective HRW on the Acceptability E-Scale (mean values of the individual items: 1.8-2.1). CONCLUSION: In Germany, HRWs play a minor role for uro-oncologic patients undergoing elective surgery. Instead, personal consultation of the treating urologist seems to be far more important. Although patients predominantly rated the provided information of the HRW as positive, only a quarter of users changed the initial choice of hospital.

Ultrasound-based "CEUS-Bosniak"classification for cystic renal lesions: an 8-year clinical experience.

PURPOSE: Renal cysts comprise benign and malignant entities. Risk assessment profits from CT/MRI imaging using the Bosniak classification. While Bosniak-IIF, -III, and -IV cover complex cyst variants, Bosniak-IIF and -III stand out due to notorious overestimation. Contrast-enhanced ultrasound (CEUS) is promising to overcome this deficit but warrants standardization. This study addresses the benefits of a combined CEUS and CT/MRI evaluation of renal cysts. The study provides a realistic account of kidney tumor boards' intricacies in trying to validate renal cysts. METHODS: 247 patients were examined over 8 years. CEUS lesions were graded according to CEUS-Bosniak (IIF, III, IV). 55 lesions were resected, CEUS-Bosniak- and CT/MRI-Bosniak-classification were correlated with histopathological diagnosis. Interobserver agreement between the classifications was evaluated statistically. 105 lesions were followed by ultrasound, and change in CEUS-Bosniak-types and lesion size were documented. RESULTS: 146 patients (156 lesions) were included. CEUS classified 67 lesions as CEUS-Bosniak-IIF, 44 as CEUS-Bosniak-III, and 45 as CEUS-Bosniak-IV. Histopathology of 55 resected lesions revealed benign cysts in all CEUS-Bosniak-IIF lesions (2/2), 40% of CEUS-Bosniak-III and 8% of CEUS-Bosniak-IV, whereas malignancy was uncovered in 60% of CEUS-Bosniak-III and 92% of CEUS-Bosniak-IV. Overall, CEUS-Bosniak-types matched CT/MRI-Bosniak types in 58% (fair agreement, κ = 0.28). CEUS-Bosniak resulted in higher stages than CT/MRI-Bosniak (40%). Ultrasound follow-up of 105 lesions detected no relevant differences between CEUS-Bosniak-types concerning cysts size. 99% of lesions showed the same CEUS-Bosniak-type. CONCLUSION: The CEUS-Bosniak classification is an essential tool in clinical practice to differentiate and monitor renal cystic lesions and empowers diagnostic work-up and patient care.

Regional Lymph Node Metastasis on Prostate Specific Membrane Antigen Positron Emission Tomography Correlates with Decreased Biochemical Recurrence-Free and Therapy-Free Survival after Radical Prostatectomy: A Retrospective Single-Center Single-Arm Observational Study.

PURPOSE: We sought to address the impact of preoperative prostate specific membrane antigen (PSMA) positron emission tomography (PET) findings prior to radical prostatectomy and pelvic lymph node dissection on biochemical recurrence and time to adjuvant or salvage treatment. MATERIALS AND METHODS: Between 2013 and 2017, 64 intermediate and 166 high risk (230) prostate cancer patients received 68Ga-PSMA-11 PET followed by radical prostatectomy and pelvic lymph node dissection. Biochemical recurrence-free and therapy-free survivalwere determined. For all time-to-event analyses, univariable and multivariable Cox proportional hazards models and univariable Kaplan-Meier analyses were applied, with a significance threshold of p <0.05. RESULTS: The overall sensitivity, specificity, positive predictive value and negative predictive value of PSMA PET for pN1 disease was 48.5%, 95.7%, 82.1% and 82.2%, respectively. Median followup was 30.2 months. Biochemical recurrence occurred in 50.4% (116) of patients and adjuvant or salvage treatment was performed in 46.5% (107). Worst biochemical recurrence-free and therapy-free survival was observed in pN1 patients who also exhibited PSMA PET positive lymph node, followed by pN1 patients without PSMA PET positive lymph node and patients without evidence of lymph node metastasis on histology and PSMA PET (median biochemical recurrence-free survival 1.7 vs. 7.5 vs. >36 months, median therapy-free survival 2.6 vs. 8.9 vs. >36 months). CONCLUSIONS: Patients with positive lymph node on PSMA PET prior to radical prostatectomy have to expect early biochemical recurrence and adjuvant/salvage therapy, despite thorough pelvic lymph node dissection. Therefore, results from PSMA PET can be used for patients' consultation and more stringent followup as well as for planning of neoadjuvant/adjuvant therapy.

One-Pot Synthesis of Alternating (Ultra-High Molecular Weight) Multiblock Copolymers via a Combination of Anionic Polymerization and Polycondensation.

This article presents a fast, straightforward synthesis approach to polymerize alternating multiblock copolymers, ultra-high molecular weight (UHMW) (homo)polymers as well as precursors for complex macromolecular topologies such as comb or barbwire architectures. The one-pot synthesis strategy proposed in this work is based on anionic polymerization via a bifunctional initiator and the subsequent linking of macro dianions with a bifunctional linker, additionally overcoming the limitations associated with the monomer reactivity. Thus, the synthetic route guarantees the repeating size of polymer blocks and an equal distribution of functional groups in precursors for complex topologies. Dianions of polystyrene (PS), polyisoprene-b-polystyrene-b-polyisoprene, and poly-2-vinylpyridine-b-polystyrene-b-poly-2-vinylpyridine are linked with α , α ' -dibromo-para-xylene to UHMW and multiblock copolymers. Multiblock copolymers with on average up to 50 well-defined alternating A and B blocks are accessible within 15 min.

Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy.

PURPOSE: To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy. METHODS: 68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets. Changes in 68Ga-PSMA uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the PERCIST scoring system with slight modification. Treatment response was defined as absence of any PSMA uptake in all target lesions on posttreatment PET (complete response, CR) or a decrease in summed SUVmean of ≥30% (partial response, PR). The appearance of a new PET-positive lesion or an increase in summed SUVmean of ≥30% (progressive disease, PD) indicated nonresponse. A moderate change in summed SUVmean (between -30% and +30%) without a change in the number of target lesions was defined as stable disease (SD). For treatment response assessment on CT, RECIST1.1 criteria were used. Radiographic responses on 68Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with biochemical response (BR). A decrease in serum PSA level of ≥50% was defined as biochemical PR. RESULTS: Biochemical PR was found in six of seven patients with mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients. 68Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%). Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target lesions on CT. 68Ga-PSMA PET and CT results corresponded in seven of 12 patients (58%, 28% to 85%). CONCLUSION: Our preliminary results suggest that 68Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance of 68Ga-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of 68Ga-PSMA PET as an imaging biomarker for response assessment.

Chromogranin A and neurone-specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration-resistant prostate cancer undergoing abiraterone therapy.

OBJECTIVE: To determine the impact of elevated neuroendocrine serum markers on treatment outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with abiraterone in a post-chemotherapy setting. PATIENTS AND METHOD: Chromogranin A (CGa) and neurone-specific enolase (NSE) were determined in serum drawn before treatment with abiraterone from 45 patients with mCRPC. Outcome measures were overall survival (OS), prostate-specific antigen (PSA) response defined by a PSA level decline of ≥50%, PSA progression-free survival (PSA-PFS), and clinical or radiographic PFS. RESULTS: The CGa and NSE serum levels did not correlate (P = 0.6). Patients were stratified in to low- (nine patients), intermediate- (18) or high-risk (18) groups according to elevation of none, one, or both neuroendocrine markers, respectively. The risk groups correlated with decreasing median OS (median OS not reached vs 15.3 vs 6.6 months; P < 0.001), decreasing median clinical or radiographic PFS (8.3 vs 4.4 vs 2.7 months; P = 0.001) and decreasing median PSA-PFS (12.0 vs 3.2 vs 2.7 months; P = 0.012). In multivariate Cox regression analysis the combination of CGa and NSE (≥1 marker positive vs both markers negative) remained significant predictors of OS, clinical or radiographic PFS, and PSA-PFS. We did not observe a correlation with PSA response (63% vs 35% vs 31%; P = 0.2). CONCLUSION: Chromogranin A and NSE did not predict PSA response in patients with mCRPC treated with abiraterone. However, we observed a correlation with shorter PSA-PFS, clinical or radiographic PFS, and OS. This might be due to an elevated risk of developing resistance under abiraterone treatment related to neuroendocrine differentiation.

A 2-Gene Panel Derived From Prostate Cancer-Enhanced Transcripts in Whole Blood Is Prognostic for Survival and Predicts Treatment Benefit in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: To determine a prognostic model derived from prostate cancer-enhanced transcripts in whole blood of castration-resistant prostate cancer (CRPC) patients and explore its applicability as a surrogate of treatment response. METHODS: Six out of twenty-three selected transcripts were identified as specific for detection of metastatic prostate cancer cells in peripheral blood using quantitative polymerase chain reaction (qPCR). Their prognostic value was explored in whole blood samples of a training cohort (n = 22 CRPC patients, New York, USA). A resulting 2-gene panel (2GP) including KLK2 and TMPRSS2 was validated in an independent cohort with pre- and post-treatment blood draws after 9-16 weeks of systemic treament (n = 86 CRPC patients, Munich, Germany). Overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and clinical PFS were analyzed. Kaplan-Meier and cox regression analyses were performed. RESULTS: An unfavorable 2GP (≥1 marker positive) identified patients with poor survival (median OS 10.0 months [95%CI 5.7-14.2] vs. not reached; P = 0.023). This was validated in an independent cohort at pre-treatment (median OS 7.8 [95%CI 6.5-9.2] vs. 17.3 months [95%CI 10.7-23.8]; P = 0.004) and post-treatment blood draw (median OS 5.0 [95%CI 0.0-10.0] vs. 18.0 months [95%CI 9.5-26.6]; P = 0.003). The 2GP independently predicted OS on multivariate analysis (hazard ratio 2.1 [95%CI 1.1-4.0]; P = 0.034) and performed better than PSA decline at correlation with OS. Conversion to favorable 2GP during treatment correlated with improved OS (7.8 to 20.9 months), PSA-PFS (2.8 to 12.0 months), and clinical PFS (4.6 to 8.0 months). CONCLUSIONS: The established 2GP is prognostic for survival at pre- and post-treatment blood draw in CRPC patients and conversion to favorable 2GP predicts treatment benefit. Prostate 76:1160-1168, 2016. © 2016 Wiley Periodicals, Inc.

Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer.

PURPOSE: Current standard imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Recently ligands of PSMA (prostate specific membrane antigen) were introduced in PET (positron emission tomography) of prostate cancer. Thus the aims of this retrospective analysis were to 1) investigate the diagnostic efficacy of (68)Ga-PSMA-PET imaging for lymph node staging in patients with prostate cancer scheduled for radical prostatectomy and 2) compare it to morphological imaging (computerized tomography and magnetic resonance tomography) with histopathological evaluation as the standard of reference. MATERIALS AND METHODS: A total of 130 patients with intermediate to high risk prostate cancer were staged with (68)Ga-PSMA-PET/magnetic resonance tomography or PET/computerized tomography from December 2012 to November 2014 before radical prostatectomy and template pelvic lymph node dissection. Histopathological findings of resected tissue were statistically correlated with the results of (68)Ga-PSMA-PET and morphological imaging in a patient and template based manner. RESULTS: Lymph node metastases were found in 41 of 130 patients (31.5%). On patient based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 65.9%, 98.9% and 88.5%, and those of morphological imaging were 43.9%, 85.4% and 72.3%, respectively. Of 734 dissected lymph node templates 117 (15.9%) showed metastases. On template based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 68.3%, 99.1% and 95.2%, and those of morphological imaging were 27.3%, 97.1% and 87.6%, respectively. On ROC analysis (68)Ga-PSMA-PET performed significantly better than morphological imaging alone on patient and template based analyses (p = 0.002 and <0.001, respectively). CONCLUSIONS: In patients with intermediate to high risk prostate cancer preoperative lymph node staging with (68)Ga-PSMA-PET proved to be superior to standard routine imaging. Thus it has the potential to replace current standard imaging for this indication if confirmed by prospective studies.

Systemic Radioligand Therapy with (177)Lu Labeled Prostate Specific Membrane Antigen Ligand for Imaging and Therapy in Patients with Metastatic Castration Resistant Prostate Cancer.

PURPOSE: We report our initial clinical experience with ß -emitting (177)Lu-PSMA-I&T ((177)Lu labeled prostate specific membrane antigen ligand for imaging and therapy) for systemic treatment of metastatic castration resistant prostate cancer. MATERIALS AND METHODS: Patients with metastatic castration resistant prostate cancer who experienced treatment failure with chemotherapy and novel androgen receptor targeted therapy were treated for 8 weeks with up to 4 cycles of (177)Lu-PSMA-I&T. We report safety data, the antitumor response with prostate specific antigen decreases and the radiographic tumor response as well as the clinical outcome with changes in ECOG (Eastern Cooperative Oncology Group) performance status and pain severity. RESULTS: The first 3 patients were treated with a lower activity of 3.7 GBq in cycle 1. Due to a favorable safety profile the activity was increased to 7.4 GBq in 19 subsequent patients who completed a total of 40 cycles. With the higher activity no grade 3/4 toxicities were observed. The main nonhematological and hematological grade 1/2 toxicities were dry mouth in 7 patients (37%), anemia in 6 (32%) and thrombopenia in 5 (25%). The proportion of patients who achieved a maximum prostate specific antigen decrease of 30% or greater, 50% or greater and 90% or greater was 56%, 33% and 11%, respectively. Combined assessment of bone and soft tissue metastases showed complete remission in 5% of patients, stable disease in 63% and progressive disease in 32%. ECOG performance status improved or was stable in 74% of patients. Of men with bone pain 58% achieved complete resolution or reduced pain. CONCLUSIONS: Radioligand therapy with (177)Lu-PSMA-I&T appears to be safe and active in heavily pretreated patients with metastatic castration resistant prostate cancer.

Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer.

PURPOSE: The aim of our study was to compare the diagnostic performance of 68Ga-PSMA PET and 99mTc bone scintigraphy (BS) for the detection of bone metastases in prostate cancer (PC) patients. METHODS: One hundred twenty-six patients who received planar BS and PSMA PET within three months and without change of therapy were extracted from our database. Bone lesions were categorized into benign, metastatic, or equivocal by two experienced observers. A best valuable comparator (BVC) was defined based on BS, PET, additional imaging, and follow-up data. The cohort was further divided into clinical subgroups (primary staging, biochemical recurrence, and metastatic castration-resistant prostate cancer [mCRPC]). Additionally, subgroups of patients with less than 30 days delay between the two imaging procedures and with additional single-photon emission computed tomography (SPECT) were analyzed. RESULTS: A total of 75 of 126 patients were diagnosed with bone metastases. Sensitivities and specificities regarding overall bone involvement were 98.7-100 % and 88.2-100 % for PET, and 86.7-89.3 % and 60.8-96.1 % (p < 0.001) for BS, with ranges representing results for 'optimistic' or 'pessimistic' classification of equivocal lesions. Out of 1115 examined bone regions, 410 showed metastases. Region-based analysis revealed a sensitivity and specificity of 98.8-99.0 % and 98.9-100 % for PET, and 82.4-86.6 % and 91.6-97.9 % (p < 0.001) for BS, respectively. PSMA PET also performed better in all subgroups, except patient-based analysis in mCRPC. CONCLUSION: Ga-PSMA PET outperforms planar BS for the detection of affected bone regions as well as determination of overall bone involvement in PC patients. Our results indicate that BS in patients who have received PSMA PET for staging only rarely offers additional information; however, prospective studies, including a standardized integrated x-ray computed tomography (SPECT/CT) protocol, should be performed in order to confirm the presented results.

Intraoperative frozen section monitoring during nerve-sparing radical prostatectomy: evaluation of partial secondary resection of neurovascular bundles and its effect on oncologic and functional outcome.

PURPOSE: Intraoperative frozen sections (IFS) of the prostate have demonstrated to be effective in reducing positive surgical margins (PSM) and biochemical recurrence (BCR). The aim of this study was to assess partial secondary resection of neurovascular bundles (NVB) and report for the first time corresponding functional results. METHODS: A total of 500 consecutive patients were included in this prospective series. All patients underwent open nerve-sparing radical prostatectomy. Intraoperatively, both posterolateral aspects of the prostate were sent for IFS. In case of PSM, additional tissue was partly resected from the prostatic bed along the NVB. BCR was the oncologic endpoint (PSA ≥ 0.2 ng/ml). The impact of IFS on PSM and BCR-free survival, and the effect of secondary partial resection of NVB on continence and erectile function (EF) recovery were analyzed by Kaplan-Meier analyses. RESULTS: Twenty-nine patients were excluded because of neoadjuvant treatment/lymph node positive disease. PSM were detected in 137/471 patients (29.1%). After secondary resection, 127/137 patients (92.7%) converted to definitive negative surgical margins (NSM). Out of 137 patients, ten (7.3%) showed persistent PSM. False-negative rate was 3.3% (11/334). Out of 471 patients, two (0.4%) showed PSM outside the IFS area. Overall, final PSM rate was 4.9% (23/471). Five-year BCR-free survival did not differ significantly in patients with primarily and converted NSM. Continence and EF recovery after 12 months were 95.8 versus 94.3%, and 65.7 versus 56.1%, respectively (all p > 0.05). CONCLUSION: IFS are highly effective in reducing PSM and avoiding compromised oncologic outcome. Partial secondary resection of the NVB ensures ns status and consequently preserves continence and EF.

Evaluation of Computed Tomography for Lymph Node Staging in Bladder Cancer Prior to Radical Cystectomy.

OBJECTIVES: To retrospectively evaluate the value of CT for lymph node (LN) staging in bladder cancer. METHODS: Two uroradiologists reviewed CT scans of 231 patients who underwent radical cystectomy and pelvic lymphadenectomy according to a predefined 12-field template. A 5-step model was used to grade the radiological likelihood of a LN to represent malignant spread based on size, configuration and structure as well as regional clustering. Statistical analyses were performed both on patient- and field-based levels. RESULTS: LN metastases were found in 59 of 231 patients (25.5%). On a patient-based level, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 52.6, 93.6, 73.2, 85.6 and 83.4%, respectively. Using the field-based approach, a total of 1,649 anatomical fields were evaluable, of which 114 fields showed malignancy (6.9%). On a field basis, sensitivity, specificity, PPV, NPV and accuracy were 30.2, 98, 51.5, 94.5 and 93.3%, respectively. Concerning local staging (pT category), the overall accuracy was 78%; overstaging occurred in 6% and understaging in 16%. CONCLUSIONS: In line with prior studies, the sensitivity of CT imaging for the detection of LN metastases was low, while high values for specificity were achieved. This was further underlined by analyzing standardized anatomical fields. Concerning local staging, postoperative changes after TURB-T rarely led to overstaging.

A robust blood gene expression-based prognostic model for castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is associated with wide variations in survival. Recent studies of whole blood mRNA expression-based biomarkers strongly predicted survival but the genes used in these biomarker models were non-overlapping and their relationship was unknown. We developed a biomarker model for CRPC that is robust, but also captures underlying biological processes that drive prostate cancer lethality. METHODS: Using three independent cohorts of CRPC patients, we developed an integrative genomic approach for understanding the biological processes underlying genes associated with cancer progression, constructed a novel four-gene model that captured these changes, and compared the performance of the new model with existing gene models and other clinical parameters. RESULTS: Our analysis revealed striking patterns of myeloid- and lymphoid-specific distribution of genes that were differentially expressed in whole blood mRNA profiles: up-regulated genes in patients with worse survival were overexpressed in myeloid cells, whereas down-regulated genes were noted in lymphocytes. A resulting novel four-gene model showed significant prognostic power independent of known clinical predictors in two independent datasets totaling 90 patients with CRPC, and was superior to the two existing gene models. CONCLUSIONS: Whole blood mRNA profiling provides clinically relevant information in patients with CRPC. Integrative genomic analysis revealed patterns of differential mRNA expression with changes in gene expression in immune cell components which robustly predicted the survival of CRPC patients. The next step would be validation in a cohort of suitable size to quantify the prognostic improvement by the gene score upon the standard set of clinical parameters.

Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients.

BACKGROUND: Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel. METHODS: CTC-counts were assessed in 122 serial samples, as continuous or categorical (<5 vs. ≥5 CTCs) variables, at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD), by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods. RESULTS: Categorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p=0.02) and 18.0 (p=0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p=0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95% CI 1.1-13.8, p=0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95% CI 0.99-1.05, p=0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95% CI 1.6-15.7, p=0.007) and 1.02 (95% CI 1.0-1.040, p=0.04). CONCLUSIONS: Categorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment.

Prospective comparison of computed tomography, diffusion-weighted magnetic resonance imaging and [11C]choline positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer patients.

PURPOSE: The aim of this study was to prospectively compare diffusion-weighted magnetic resonance imaging (DWI) and [(11)C]choline positron emission tomography/computed tomography (PET/CT) with computed tomography (CT) for preoperative lymph node (LN) staging in prostate cancer (PCa) patients. METHODS: Between June 2010 and May 2012, CT, DWI and [(11)C]choline PET/CT were performed preoperatively in 33 intermediate- and high-risk PCa patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) including obturator fossa and internal, external and common iliac fields. Patient- and field-based performance characteristics for all three imaging techniques based on histopathological results are reported. Imaging techniques were compared by means of the area under the curve (AUC). RESULTS: LN metastases were detected in 92 of 1,012 (9%) LNs from 14 of 33 (42%) patients. On patient-based analysis, sensitivity, specificity and accuracy for CT were 57, 68 and 64%, respectively, for DWI were 57, 79 and 70%, respectively, and for [(11)C]choline PET/CT were 57, 90 and 76%, respectively. On field-based analysis, these numbers for CT were 47, 94 and 88%, respectively, for DWI were 56, 97 and 92%, respectively, and for [(11)C]choline PET/CT were 62, 96 and 92%, respectively. Neither DWI nor [(11)C]choline PET/CT performed significantly better than CT on pairwise comparison of patient- and field-based results. CONCLUSION: All three imaging techniques exhibit a rather low sensitivity with less than two thirds of LN metastases being detected on patient- and field-based analysis. Overall diagnostic efficacy did not differ significantly between imaging techniques, whereas distinct performance characteristics, esp. patient-based specificity, were best for [(11)C]choline PET/CT followed by DWI and CT.

Preoperative lymph node staging in patients with primary prostate cancer: comparison and correlation of quantitative imaging parameters in diffusion-weighted imaging and 11C-choline PET/CT.

PURPOSE: To compare the diagnostic performance of DWI and 11C-choline PET/CT in the assessment of preoperative lymph node status in patients with primary prostate cancer. MATERIAL AND METHODS: Thirty-three patients underwent DWI and 11C-choline PET/CT prior to prostatectomy and extended pelvic lymph node dissection. Mean standardised uptake value (SUV(mean)) and mean apparent diffusion coefficient (ADC) of 76 identified lymph nodes (LN) were measured and correlated with histopathology. ADC values and SUVs were compared using linear regression analysis. RESULTS: A significant difference between benign and malignant LN was observed for ADC values (1.17 vs. 0.96 × 10(-3) mm(2)/s; P < 0.001) and SUV(mean) (1.61 vs. 3.20; P < 0.001). ROC analysis revealed an optimal ADC threshold of 1.01 × 10(-3) mm(2)/s for differentiating benign from malignant LN with corresponding sensitivity/specificity of 69.70%/78.57% and an area under the curve (AUC) of 0.785. The optimal threshold for SUV(mean) was 2.5 with corresponding sensitivity/specificity of 69.72%/90.48% and with an AUC of 0.832. ADC values and SUV(mean) showed a moderate significant inverse correlation (r = -0.63). CONCLUSION: Both modalities reveal similar moderate diagnostic performance for preoperative lymph node staging of prostate cancer, not justifying their application in routine clinical practice at this time. The only moderate inverse correlation between ADC values and SUV(mean) suggests that both imaging parameters might provide complementary information on tumour biology. KEY POINTS: • Conventional imaging shows low performance for lymph node staging in prostate cancer. • DWI and 11C-choline PET/CT both provide additional functional information • Both functional modalities reveal only moderate diagnostic performance.

Prognostic value of 11C-choline PET/CT and CT for predicting survival of bladder cancer patients treated with radical cystectomy.

BACKGROUND: In patients with bladder cancer (BCa) preoperative staging with (11)C-choline positron emission tomography-computed tomography (PET/CT) could be used to derive prognostic information and hence stratify patients preoperatively with respect to disease management. METHODS: From June 2004 to May 2007, 44 patients with localized BCa were staged with (11)C-choline PET/CT before radical cystectomy. The results of imaging were correlated to overall survival (OS) and cumulative incidence of cancer-specific death (CSD). RESULTS: There was no statistically significant difference in OS and CSD between the patient groups when stratified for organ-confined versus non-organ-confined disease or lymph node involvement defined by either (11)C-choline PET/CT (OS: p = 0.262, hazard ratio [HR] = 1.60; p = 0.527, HR = 0.76; CSD: p = 0.144, HR = 2.25; p = 0.976, HR = 0.98) or CT (OS: p = 0.518, HR = 1.34; p = 0.228, HR = 1.67; CSD: p = 0.323, HR = 1.90; p = 0.136, HR = 2.38). The limitation of this study is the small number of included patients. CONCLUSION: In our prospective trial neither CT nor (11)C-choline PET/CT were able to sufficiently predict OS or CSD in BCa patients treated with radical cystectomy albeit trends and moderately increased HRs could be demonstrated without significant differences between CT or (11)C-choline PET/CT. However, these trends might prove statistically significant in bigger patient cohorts. Therefore initial transsectional imaging might be of clinical relevance in respect to prognosis and could play a role in the counseling of BCa patients.

Biochemical Response of <0.1 ng/ml Predicts Therapy-free Survival of Prostate Cancer Patients following Prostate-specific Membrane Antigen-targeted Salvage Surgery.

BACKGROUND: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. OBJECTIVE: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022). INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. RESULTS AND LIMITATIONS: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. PATIENT SUMMARY: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.