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 [ 68 Ga]-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<0.01) predictor for PCa patients with GS ≥8 tumors and pN1 status. Conclusion: RF derived from PSMA PET discriminated between PCa and non-PCa tissue within the prostate. Additionally, the texture feature QSZHGE discriminated between GS 7 and GS ≥8 tumors and between patients with pN1 and pN0 disease. Our results support the role of RF in PSMA PET as a new tool for non-invasive PCa discrimination and characterization of its biological properties.

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BackgroundFocal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed that multiparametric MRI (mpMRI) or PSMA PET alone could be used for boost volume definition. However, other studies proposed that the combined usage of both has the highest sensitivity in detection of intraprostatic lesions. The aim of this study was to demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of radiation therapy dose painting using 68Ga-HBED-CC PSMA PET/CT, mpMRI or the combination of both in primary PCa.MethodsTen patients underwent PSMA PET/CT and mpMRI followed by prostatectomy. Three gross tumour volumes (GTVs) were created based on PET (GTV-PET), mpMRI (GTV-MRI) and the union of both (GTV-union). Two plans were generated for each GTV. Plan95 consisted of whole-prostate IMRT to 77 Gy in 35 fractions and a simultaneous boost to 95 Gy (Plan95PET/Plan95MRI/Plan95union). Plan80 consisted of whole-prostate IMRT to 76 Gy in 38 fractions and a simultaneous boost to 80 Gy (Plan80PET/Plan80MRI/Plan80union). TCPs were calculated for GTV-histo (TCP-histo), which was delineated based on PCa distribution in co-registered histology slices. NTCPs were assessed for bladder and rectum.ResultsDose constraints of published protocols were reached in every treatment plan. Mean TCP-histo were 99.7% (range: 97%–100%) and 75.5% (range: 33%–95%) for Plan95union and Plan80union, respectively. Plan95union had significantly higher TCP-histo values than Plan95MRI (p = 0.008) and Plan95PET (p = 0.008). Plan80union had significantly higher TCP-histo values than Plan80MRI (p = 0.012), but not than Plan80PET (p = 0.472).Plan95MRI had significantly lower NTCP-rectum than Plan95union (p = 0.012). No significant differences in NTCP-rectum and NTCP-bladder were observed for all other plans (p > 0.05).ConclusionsIMRT dose escalation on GTVs based on mpMRI, PSMA PET/CT and the combination of both was feasible. Boosting GTV-union resulted in significantly higher TCP-histo with no or minimal increase of NTCPs compared to the other plans.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1036-8) contains supplementary material, which is available to authorized users.

Accurate detection of prostate cancer lymph node metastases (LNM) through PET/CT before lymphadenectomy is crucial for successful therapy. PET/CT with choline derivatives used to be the standard tool for imaging metastases, whereas 68 Ga-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 (TDs) within LNM. Methods: Documenting the switch from the use of 18 F-choline to 68 Ga-PSMA in 2014, we used 2 patient cohorts undergoing a template lymphadenectomy because of a PET/CT indicating LNM. Forty-four and 40 patients underwent PET/CT with 18 F-choline or 68 Ga-PSMA ligand, respectively. In total, 226 LNM (125 18 F-choline, 101 68 Ga-PSMA) originated from 73 salvage lymphadenectomies at biochemical recurrence and from 11 primary lymphadenectomies at radical prostatectomy. LNM eligible for direct correlation of PET/CT to histopathology were identified from lymphadenectomies conducted in small anatomic subregions, with 1 LNM (condition 1) or 1-2 LNM (condition 2). Longitudinal and short diameters of TD within LNM were determined by histopathology, allowing linking of the size of TD in LNM to the detection threshold of PET/CT. Diameters associated with a detection rate of 50% and 90% (d 50% , d 90%) were calculated on the basis of logistic growth curve models fitted. Results: Gleason score, number of removed LNs, and subregions for lymphadenectomy per patient did not differ significantly between the 18 F-choline and 68 Ga-PSMA groups. The median prostate-specific antigen level at imaging and number of LNM per patient were significantly higher in the 18 F-choline group (3.4 ng/mL, n 5 34) than in the 68 Ga-PSMA group (2.2 ng/mL, n 5 28; both P , 0.05). Longitudinal and short diameters of TD in LNM to reach d 90% were 11.2 and 7.4 mm, respectively, for 18 F-choline PET/CT and 6.3 and 4.9 mm, respectively, for 68 Ga-PSMA PET/CT. Corresponding diameters to reach d 50% were 5.5 and 3.3 mm, respectively, for 18 F-choline PET/CT and 3.7 and 2.3 mm, respectively, for 68 Ga-PSMA PET/CT. Detection rates were significantly higher under 68 Ga-PSMA (P 5 0.005 and 0.04 for longitudinal and short diameter). Conclusion: 68 Ga-PSMA PET/CT is superior to 18 F-choline PET/CT in the detection of LNM. Whether those results will lead to an improved patient outcome after 68 Ga-PSMA PETguided therapy needs to be investigated by further studies.

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.

Ex situ analysis at the level of single LN showed that In-PSMA-617 had excellent ability to discriminate between affected and nonaffected LN in our patients with PCa. This tracer characteristic is a prerequisite for in vivo real-time measurements during surgery.

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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 111 In-labelled PSMA ligand (DKFZ-617, referred to as [ 111 In]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, [ 111 In]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 ). [ 111 In]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: [ 111 In]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.