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Purpose Accurate definition of the intraprostatic gross tumor volume (GTV) is crucial for diagnostic and therapeutic approaches in patients with primary prostate cancer (PCa). The optimal methodology for contouring of GTV using Prostate specific membrane antigen positron emission tomography (PSMA-PET) information has not yet been defined. Methods and Materials PCa patients who underwent a [68Ga]PSMA-11-PET/CT followed by radical prostatectomy were prospectively enrolled (n = 20). Six observer teams with different levels of experience and using different PET image scaling techniques performed manual contouring of GTV. Additionally, semi-automatic segmentation of GTVs was performed using SUVmax thresholds of 20–50%. Coregistered histopathological gross tumor volume (GTV-Histo) served as reference. Inter-observer agreement was assessed by calculating the Dice similarity coefficient (DSC). Results Most contouring methods provided high sensitivity and specificity. For manual delineation, scaling the PET images from SUVmin-max: 0–5 resulted in high sensitivity (>86%). The highest specificity (100%) was obtained by scaling the PET images from SUVmin-max: 0-SUVmax. High interobserver agreement (median DSC 0.8) was observed when using the same PET image scaling technique (PET images SUVmin-max: 0–5). For semi-automatic segmentation, a low SUVmax threshold of 20% optimized sensitivity (SUVmax threshold 20%, 100% sensitivity, 32% of prostatic volume), whereas a higher threshold optimized specificity (SUVmax threshold 40%–50%, 100% specificity). Conclusions Contouring of regions with high tracer-uptake resulted in very high specificities and should be used for biopsy guidance. Both manual and semi-automatic approaches using validated SUV scaling (SUVmin-max: 0–5) or thresholding (20%) may provide high sensitivity, and should be considered for PSMA-PET-based focal therapy approaches.

Purpose: To evaluate the performance of radiomic features (RF) derived from PSMA PET for intraprostatic tumor discrimination and non-invasive characterization of Gleason score (GS) and pelvic lymph node status. Patients and methods: Patients with prostate cancer (PCa) who underwent [68Ga]-PSMA-11 PET/CT followed by radical prostatectomy and pelvic lymph node dissection were prospectively enrolled (n=20). Coregistered histopathological gross tumor volume (GTV-Histo) in the prostate served as reference. 133 RF were derived from GTV-Histo and from manually created segmentations of the intraprostatic tumor volume (GTV-Exp). Spearman´s correlation coefficients (ρ) were assessed between RF derived from the different GTVs. We additionally analyzed the differences in RF values for PCa and non-PCa tissues. Furthermore, areas under receiver-operating characteristics curves (AUC) were calculated and uni- and multivariate analyses were performed to evaluate the RF based discrimination of GS 7 and ≥8 disease and of patients with nodal spread (pN1) and non-nodal spread (pN0) in surgical specimen. The results found in the latter analyses were validated by a retrospective cohort of 40 patients. Results: Most RF from GTV-Exp showed strong correlations with RF from GTV-Histo (86% with ρ>0.7). 81% and 76% of RF from GTV-Exp and GTV-Histo significantly discriminated between PCa and non-PCa tissue. The texture feature QSZHGE discriminated between GS 7 and ≥8 considering GTV-Histo (AUC=0.93) and GTV-Exp (prospective cohort: AUC=0.91 / validation cohort: AUC=0.84). QSZHGE also discriminated between pN1 and pN0 disease considering GTV-Histo (AUC=0.85) and GTV-Exp (prospective cohort: AUC=0.87 / validation cohort: AUC=0.85). In uni- and multivariate analyses including patients of both cohorts QSZHGE was a statistically significant (p

The introduction of tracers targeting the prostate-specific membrane antigen (PSMA) has revolutionized PET imaging of acinar prostate adenocarcinoma. In general, an increasing PSMA expression is assumed with increasing dedifferentiation. Whereas loss of PSMA expression has been reported in case of neuroendocrine dedifferentiation, we present a patient with acinar prostate adenocarcinoma with a loss of PSMA expression after chemotherapy on PET/CT and in histological and immunohistochemical analyses. All tissue samples indicated the retention of acinar features but no expression of neuroendocrine markers (NSE, synaptophysin, chromogranin, and CD56), corresponding to nonelevated serum NSE.

Implementation of advanced imaging techniques like multiparametric magnetic resonance imaging (mpMRI) or Positron Emission Tomography (PET) in radiation therapy (RT) planning of patients with primary prostate cancer demands several preconditions: accurate staging of the extraprostatic and intraprostatic tumor mass, robust delineation of the intraprostatic gross tumor volume (GTV) and a reproducible characterization of the prostate cancer's biological properties. In the current review we searched for the currently available imaging techniques and we discussed their ability to fulfill these preconditions. We found that current pretreatment imaging was mainly performed with mpMRI and/or Prostate-specific membrane antigen PET imaging. Both techniques offered an accurate detection of the extraprostatic and intraprostatic tumor burden and had a major impact on RT concepts. However, some studies postulated that mpMRI and PSMA PET had complementary information for intraprostatic GTV detection. Moreover, interobserver differences for intraprostatic tumor delineation based on mpMRI were observed. It is currently unclear whether PET based GTV delineation underlies also interobserver heterogeneity. Further research is warranted to answer whether multimodal imaging is able to visualize biological processes related to prostate cancer pathophysiology and radiation resistance.

PURPOSE: Intraoperative identification of lymph node (LN) metastases (LNM) detected on preoperative PSMA PET/CT may be facilitated by PSMA radioguided surgery with the use of a gamma probe. We evaluated the uptake of 111In-labelled PSMA ligand DKFZ-617 (referred to as 111In-PSMA-617) in unaffected LN and LNM at the level of single LN. METHODS: Six patients with prostate cancer (PCa) with suspicion of LNM on preoperative PSMA PET/CT underwent 111In-PSMA-617-guided lymphadenectomy (LA; four salvage LA and two primary LA). 111In-PSMA-617 (109 ± 5 MBq). was injected Intravenously 48 h prior to surgery Template LAs were performed in small subregions: common, external, obturator and internal iliac vessels, and presacral and retroperitoneal subregions (n = 4). Samples from each subregion were isolated aiming at the level of single LN. Uptake was measured ex situ using a germanium detector. Receiver operating characteristic (ROC) analysis was performed based on 111In-PSMA-617 uptake expressed as standardized uptake values normalized to lean body mass (SUL). RESULTS: Overall 310 LN (mean 52 ± 19.7) were removed from 74 subregions (mean 12 ± 3.7). Of the 310 LN, 35 turned out to be LNM on histopathology. Separation of the samples from all subregions resulted in 318 single specimens: 182 PCa-negative LN samples with 275 LN, 35 single LNM samples, 3 non-nodal PCa tissue samples and 98 fibrofatty tissue samples. The median SULs of nonaffected LN (0.16) and affected LN (13.2) were significantly different (p