Cordula Annette Jilg

Introduction: Quantitative evaluation of prostate-specific membrane antigen (PSMA)- targeting positron emission tomography/computer tomography (PSMA PET/CT) remains challenging but is urgently needed for the use of standardized PET-based response criteria, such as the PSMA PET/CT consensus statement or RECIP 1.0. A recent study evaluated the prognostic value of whole-body tumor volume using a semiautomatical method relying on a 50% threshold of maximum lesion standardized uptake value (PSMA_TV50). In the present study, we analyzed the suitability of this approach comparing ¹⁸F-PSMA-1007 to ⁶⁸Ga-PSMA-11 PET/CT scans and the potential of PSMA_TV50 for the prediction of overall survival (OS) in patients before ¹⁷⁷Lu-PSMA-radioligand therapy (PSMA RLT). Moreover, PSMA_TV50 was integrated into the PSMA PET/CT consensus statement as well as RECIP 1.0 and the prognostic value of these response classification systems was compared. Methods: This retrospective study included 70 patients with metastatic castration-resistant prostate cancer undergoing PSMA RLT. 33 patients were monitored by ⁶⁸Ga-PSMA-11 PET/CT and 37 patients by ¹⁸F-PSMA-1007 PET/CT. PET/CT scans before (baseline) and at the end of PSMA RLT after 2-4 cycles (follow-up) were separately analyzed by two readers. PSMA_TV50 at baseline and its change to follow-up (ΔPSMA_TV50; expressed as a ratio) were correlated with OS using Cox proportional hazard regression. The results of both subgroups were compared. The integration of ΔPSMA_TV50 in existing response classification systems was evaluated. To assess and compare the discriminatory strength of these classification systems, Gönen & Heller concordance probability estimates (CPE) were calculated. Results: PSMA_TV50-determination was technically feasible in all examinations. A higher PSMA_TV50 at baseline and a higher ΔPSMA_TV50 were strongly associated with a shorter OS for both ⁶⁸Ga-PSMA-11 (PSMA_TV50: HR 1.29 [1.05 – 1.55], p=0.009; ΔPSMA_TV50: HR 1.83 [1.08 – 3.09], p=0.024) and ¹⁸F-PSMA-1007 (PSMA_TV50: HR 1.84 [1.13 – 2.99], p=0.014; ΔPSMA_TV50: HR 1.23 [1.04 – 1.51], p=0.03). Response assessment provided high discriminatory power for OS for the PSMA PET/CT consensus statement (CPE 0.73) as well as RECIP 1.0 (CPE 0.74). Conclusion: PSMA_TV50 and ΔPSMA_TV50 proved to be predictive of OS not only for ⁶⁸Ga-PSMA-11 but also for ¹⁸F-PSMA-1007 PET/CT scans. Subsequent integration of ΔPSMA_TV50 into the PSMA PET/CT consensus statement and RECIP 1.0 provided equally high prognostic value for both classification systems.

Introduction: Robot-assisted radical prostatectomy (RARP) is a surgical treatment option for prostate cancer (PC). Quality in RARP depends on the surgeon´s operative volume and expertise. When implementing RARP, it is standard practice to hire a pre-trained surgeon. The aim of our study was to investigate the transferability of quality in RARP. Patients and Methods: We analyzed two consecutive retrospective cohorts of 100 and 108 men, respectively, who underwent RARP at two different centers and on whom surgery was performed by the same surgeon. Results: There were more men with high-grade PC in Cohort 1: 25/100 (25.0%) vs. 9/108 (8.3%), p < 0.01, and infiltration of the seminal vesicles was more frequent (23/100 (23.0%) vs. 10/108 (9.2%), p < 0.01). In Cohort 2, the duration of surgery was shorter and blood loss was lower: 149 (134–174) vs. 172 min (150–196), p < 0.01 and 300 (200–400) vs. 131 (99–188) mL, p < 0.01. No difference was found in the proportion of positive surgical margins in the T2 cohort (8.8% vs. 8.2%, p = 1.00). Conclusion: The procedural and oncological outcome parameters of Cohort 2 do not appear to be inferior to the results obtained for the first cohort. The quality of RARP is transferable if a pre-trained surgeon is hired.

Background: In prostate cancer (PC) diagnosis, additional systematic biopsy (SB) is recommended to complement MRI-targeted biopsy (TB) to address the limited sensitivity of TB alone. The combination of TB+SB is beneficial for diagnosing additional significant PC (sPC) but harmful in terms of the additional diagnosis of indolent PC (iPC), morbidity, and resource expenditures. We aimed to investigate the benefit of additional SB and to identify predictors for this outcome. Methods: We analyzed the frequency of upgrading to sPC by additional SB in a retrospective single-center cohort of 1043 men. Regression analysis (RA) was performed to identify predictors for this outcome. Reclassification rates of ISUP grade groups between prostate biopsy and a subsequent radical prostatectomy were assessed. Results: Additional SB led to upgrading to sPC in 98/1043 men (9.4%) and to the additional diagnosis of iPC in 71/1043 (6.8%). In RA, men harboring a PI-RADS 2-4 lesion were more likely to have TB results upgraded by SB (p < 0.01) compared to PI-RADS 5 men. When analyzing reclassification rates, additional SB reduced the upgrading to sPC from 43/214 (20.1%) to 8/214 (3.7%). In the PI-RADS 5 subgroup, this difference decreased: 4/87 (4.7%) with TB only vs. 1/87 (1.2%) with TB+SB. Conclusion: Men with a PI-RADS 5 lesion may obviate additional SB.

Von Hippel–Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m², which decreased to 76.6 ± 8.0 mL/min/1.73 m² after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.

Background: Systematic biopsy (SB) according to the Ginsburg scheme (GBS) is widely used to complement MRI-targeted biopsy (MR-TB) for optimizing the diagnosis of clinically significant prostate cancer (sPCa). Knowledge of the GBS’s blind sectors where sPCa is missed is crucial to improve biopsy strategies. Methods: We analyzed cancer detection rates in 1084 patients that underwent MR-TB and SB. Cancerous lesions that were missed or underestimated by GBS were re-localized onto a prostate map encompassing Ginsburg sectors and blind-sectors (anterior, central, basodorsal and basoventral). Logistic regression analysis (LRA) and prostatic configuration analysis were applied to identify predictors for missing sPCa with the GBS. Results: GBS missed sPCa in 39 patients (39/1084, 3.6%). In 27 cases (27/39, 69.2%), sPCa was missed within a blind sector, with 17/39 lesions localized in the anterior region (43.6%). Neither LRA nor prostatic configuration analysis identified predictors for missing sPCa with the GBS. Conclusions: This is the first study to analyze the distribution of sPCa missed by the GBS. GBS misses sPCa in few men only, with the majority localized in the anterior region. Adding blind sectors to GBS defined a new sector map of the prostate suited for reporting histopathological biopsy results.

Purpose: Identification of suspicious PSMA-PET/CT-positive lymph node (LN) metastases (LNM) from prostate cancer (PCa) during lymphadenectomy (LA) is challenging. We evaluated an ¹¹¹In-labelled PSMA ligand (DKFZ-617, referred to as [¹¹¹In]PSMA-617) as a γ-emitting tracer for intraoperative γ-probe application for resected tissue samples in PCa patients. Forty-eight hours prior to LA, [¹¹¹In]PSMA-617 was administered intravenously in 23 patients with suspected LNM on PSMA-PET/CT (n = 21 with biochemical relapse, n = 2 at primary therapy). Resected tissue samples (LN, LNM and fibrofatty tissue) were measured ex situ by a γ-probe expressed as counts per second (CPS_norm). [¹¹¹In]PSMA-617 tissue sample uptake was measured by a germanium detector for verification and calculated as %IA_lbm (percent injected activity per kilogram lean body mass at time of surgery). Based on a clinical requirement for a specificity > 95%, thresholds for both ex situ measurements were chosen accordingly. Correlation of the results from PET/CT, γ-probe and germanium detector with histopathology was done. Results: Eight hundred sixty-four LNs (197 LNM) were removed from 275 subregions in 23 patients, on average 8.6 ± 14.9 LNM per patient. One hundred four of 275 tissue samples showed cancer. Median γ-probe and germanium detector results were significantly different between tumour-affected (33.5 CPS_norm, 0.71 %IA_lbm) and tumour-free subregions (3.0 CPS_norm, 0.03 %IA_lbm) (each p value < 0.0001). For the chosen γ-probe cut-off (CPS_norm > 23) and germanium detector cut-off (%IA_lbm > 0.27), 64 and 74 true-positive and 158 true-negative samples for both measurements were identified. Thirty-nine and 30 false-negative and 6 and 5 false-positive tissue samples were identified by γ-probe and germanium detector measurements. Conclusion: [¹¹¹In]PSMA-617 application for LA is feasible in terms of an intraoperative real-time measurement with a γ-probe for detection of tumour-affected tissue samples. γ-probe results can be confirmed by precise germanium detector measurements and were significantly different between tumour-affected and tumour-free samples.

Introduction: Accurate detection of prostate cancer lymph node (LN) metastases (LNM) through PET/CT prior to lymphadenectomy (LA) is crucial for successful therapy. PET/CT with choline-derivatives used to be the standard tool for imaging metastases, whereas ⁶⁸Ga-PSMA-(prostate-specific membrane antigen)-PET/CT was introduced recently. Both PET-techniques were investigated with respect to what extent the detection rate of LNM depends on the size of tumor deposits (TD) within LNM. Methods: Documenting the switch from the use of ¹⁸F-choline to ⁶⁸Ga-PSMA in 2014, we used two patient cohorts undergoing a template LA because of a PET/CT indicating LNM. 44 and 40 patients had PET/CT with ¹⁸F-choline or ⁶⁸Ga-PSMA-ligand. 226 LNM (125 ¹⁸F-choline, 101 ⁶⁸Ga-PSMA) originated from 73 salvage LAs at biochemical recurrence and from 11 primary LAs at radical prostatectomy. LNM eligible for direct correlation of PET/CT to histopathology were identified from LAs conducted in small anatomical subregions with 1 LNM (condition 1) or 1-2 LNM (condition 2). Longitudinal and short diameter of TD within LNM were determined by histopathology allowing to link the size of TD in LNM to the detection threshold of PET/CT. Diameters associated with a detection rate of 50% and 90% (d50%, d90%) were calculated based on logistic growth curve models fitted. Results: Gleason-score, number of removed LN and subregions for LA per patient did not differ significantly between the ¹⁸F-choline-and ⁶⁸Ga-PSMA-group. Median PSA-level at imaging and number of LNM per patient was significantly higher in the ¹⁸F-choline-group (3.4 ng/ml, n = 34) compared to the ⁶⁸Ga-PSMA-group (2.2 ng/ml, n = 28; both p18F-choline-PET/CT and 6.3 mm respectively 4.9 mm for ⁶⁸Ga-PSMA-PET/CT. Corresponding diameters to reach d50% were 5.5 mm and 3.3 mm for ¹⁸F-choline-PET/CT and 3.7 mm and 2.3 mm for ⁶⁸Ga-PSMA-PET/CT, respectively. Detection rates were significantly higher under ⁶⁸Ga-PSMA (P = 0.005 and P = 0.04 for longitudinal and short diameter). Conclusion: ⁶⁸Ga-PSMA-PET/CT is superior in the detection of LNM compared to ¹⁸F-choline-PET/CT. Whether those results will lead to an improved patient outcome after ⁶⁸Ga-PSMA-PET-guided therapy needs to be investigated by further studies.