Value of 68Ga-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [18F]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study.

OBJECTIVES: The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [68Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [18F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI). METHODS: This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [68Ga]Ga-RM2 and [18F]FCH PET-CT findings were correlated with mpMRI and histopathologic results. RESULTS: Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [68Ga]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [18F]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [68Ga]Ga-RM2 PET-CT was higher compared to that of [18F]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group (p = 0.01) and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [68Ga]Ga-RM2 and [18F]FCH PET-CT in the intraprostatic malignant lesions ([68Ga]Ga-RM2: mean SUVmax: 5.98 ± 4.13, median: 4.75; [18F]FCH: mean SUVmax: 6.08 ± 2.74, median: 5.5; p = 0.13). CONCLUSIONS: [68Ga]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks. KEY POINTS: • [68Ga]Ga-RM2 is a promising PET tracer with a high detection rate for intraprostatic PCa especially in intermediate-risk prostate cancer patients. • GRPr-based imaging seems to play a complementary role to choline-based or PSMA-based PET/CT imaging in selected low- and intermediate-risk PCa patients for better characterization and eventually biopsy guidance of prostate cancer disease.

Radiologists' Contribution to Variation in Detecting Clinically Significant Prostate Cancer in Men With Prostate MRI.

OBJECTIVE: Assess radiologists' contribution to variation in clinically significant prostate cancer (csPCa) detection in patients with elevated prostate-specific antigen (PSA) and multiparametric MRI (mpMRI). METHODS: This institutional review board-approved, retrospective cohort study was performed at a tertiary, academic, National Cancer Institute-designated Comprehensive Cancer Center with a multidisciplinary prostate cancer program. Men undergoing mpMRI examinations from January 1, 2015, to December 31, 2019, with elevated PSA (≥4 ng/mL) and biopsy within 6 months pre- or post-MRI or prostatectomy within 6 months post-mpMRI were included. Univariate and multivariable hierarchical logistic regression assessed impact of patient, provider, mpMRI examination, mpMRI report, and pathology factors on the diagnosis of Grade Group ≥ 2 csPCa. RESULTS: Study cohort included 960 MRIs in 928 men, mean age 64.0 years (SD ± 7.4), and 59.8% (555 of 928) had csPCa. Interpreting radiologist was not significant individually (P > .999) or combined with mpMRI ordering physician and physician performing biopsy or prostatectomy (P = .41). Prostate Imaging Reporting and Data System (PI-RADS) category 2 (odds ratio [OR] 0.18, P = .04), PI-RADS category 4 (OR 2.52, P < .001), and PI-RADS category 5 (OR 4.99, P < .001) assessment compared with no focal lesion; PSA density of 0.1 to 0.15 ng/mL/cc (OR 2.46, P < .001), 0.15 to 0.2 ng/mL/cc (OR 2.77, P < .001), or ≥0.2 ng/mL/cc (OR 4.52, P < .001); private insurance (reference = Medicare, OR 0.52, P = .001), and unambiguous extraprostatic extension on mpMRI (OR 2.94, P = .01) were independently associated with csPCa. PI-RADS 3 assessment (OR 1.18, P = .56), age (OR 0.99, P = .39), and African American race (OR 0.90, P = .75) were not. DISCUSSION: Although there is known in-practice variation in radiologists' interpretation of mpMRI, in our multidisciplinary prostate cancer program we found no significant radiologist-attributable variation in csPCa detection.

Single fraction of HDR brachytherapy for prostate cancer: Results of the SiFEPI phase II prospective trial.

Purpose: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/Methods: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. Results: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. Conclusions: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

Rectal preparation significantly improves prostate imaging quality: Assessment of the PI-QUAL score with visual grading characteristics.

PURPOSE: To investigate the effects of a rectal preparation regimen, that consisted of a rectal cleansing enema and an endorectal gel filling protocol, on prostate imaging quality (PI-QUAL). METHODS: Multiparametric MRI (mpMRI) was performed in 150 consecutive patients divided into two groups of 75 patients. One group received a rectal preparation with a cleansing enema and endorectal gel filling (median age 65.3 years, median PSA level 6 ng/ml). The other patient group did not receive such a preparation (median age 64 years, median PSA level 6 ng/ml). Two uroradiologists independently rated general image quality and lesion visibility on diffusion-weighted imaging (DWI), T2-weighted (T2w), and dynamic contrast-enhanced (DCE) images using a five-point ordinal scale. In addition, two uroradiologists assigned PI-QUAL scores, using the dedicated scoring sheet. Data sets were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/ area under the curve (AUC) analysis. RESULTS: VGC revealed significantly better general image quality for DWI (AUC R1 0.708 (0.628-0.779 CI, p < 0.001; AUC R2 0.687 (0.606-0.760 CI, p < 0.001) and lesion visibility for both readers (AUC R1 0.729 (0.607-0.831 CI, p < 0.001); AUC R2 0.714 (0.590-0.818CI, p < 0.001) in the preparation group. For T2w imaging, rectal preparation resulted in significantly better lesion visibility for both readers (R1 0.663 (0.537-0.774 CI, p = 0.014; R2 0.663 (0.537-0.774 CI, p = 0.014)). Averaged PI-QUAL scores were significantly improved with rectal preparation (AUC R3/R4 0.667, CI 0.581-0.754, p < 0.001). CONCLUSION: Rectal preparation significantly improved prostate imaging quality (PI-QUAL) and lesion visibility. Hence, a rectal preparation regimen consisting of a rectal cleansing enema and an endorectal gel filling could be considered.

Role of mpMRI in Benign Prostatic Hyperplasia Assessment and Treatment.

PURPOSE OF REVIEW: To summarize the role of prostate MRI in the assessment and treatment of benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS). RECENT FINDINGS: BPH/LUTS is a very common source of morbidity in aging men. mpMRI has become an increasingly popular modality for prostate imaging due to its ability to provide exceptional anatomic detail. This has allowed for MRI classification of BPH and detailed assessment of response to various BPH treatment modalities, including simple prostatectomy and transurethral resection of the prostate as well as newer methods like UroLift and prostatic artery embolization. MRI will continue to be a useful tool in the diagnosis and management of BPH/LUTS and provides useful information about the efficacy of a variety of available treatment options. Further studies are needed to fully characterize the effects of newer BPH interventions on mpMRI.

[68Ga-]PSMA-11 PET/CT and multiparametric MRI for gross tumor volume delineation in a slice by slice analysis with whole mount histopathology as a reference standard - Implications for focal radiotherapy planning in primary prostate cancer.

BACKGROUND AND PURPOSE: Focal therapies are a promising approach to treat prostate cancer (PCa) more precisely instead of conventional whole gland treatment. Nowadays, multiparametric MRI (mpMRI) is routinely used for gross tumor volume (GTV) delineation. The aim of our study was to compare PSMA-PET/CT and mpMRI for the delineation of intraprostatic tumor burden by using whole mount histopathology as a reference standard. MATERIAL AND METHODS: 17 prospectively enrolled patients with primary PCa underwent [68Ga-]PSMA-11 PET/CT and mpMRI before radical prostatectomy. PSMA-PET/CT, mpMRI and histopathology of the resected specimens were co-registered. Two teams of experts generated GTV contours for mpMRI and PET, respectively. The imaging was validated on a lesion level and slice by slice in quadrants based on the distribution of PCa in histopathology. Overall, 772 quadrants were analyzed with 414 being true positive for tumor (53.6%). RESULTS: Median tumor volumes were 10.4 ml for GTV-histo, 10.8 ml for PSMA-PET and 4.5 ml for mpMRI. Median tumor volume in mpMRI was significant (p < 0.05) smaller than GTV-PET and GTV-histo, respectively. The sensitivity and specificity were 86% and 87% for PSMA-PET, 58% and 94% for mpMRI and 91% and 84% for their GTV-union. In 133 quadrants PSMA-PET/CT correctly identified tumor where mpMRI found none. MpMRI identified 19 true positive quadrants exclusively. CONCLUSION: Our investigation demonstrates an increased consensus of PSMA-PET with histopathology compared to mpMRI for intraprostatic GTV delineation, especially with a higher sensitivity. Additionally mpMRI contours underestimate tumor volume significantly. Thus PSMA-PET may be a complementary augmentation for GTV delineation in focal therapies.

Multi-disciplinary and shared decision-making approach in the management of organ-confined prostate cancer.

Decision-making in the management of organ-confined prostate cancer is complex as it is based on multi-factorial considerations. It is complicated by a multitude of issues, which are related to the patient, treatment, disease, availability of equipment(s), expertise, and physicians. Combination of all these factors play a major role in the decision-making process and provide for an interactive decision-making preferably in the multi-disciplinary team (MDT) meeting. MDT decisions are comprehensive and are often based on all factors including patients' biological status, disease and its aggressiveness, and physician and centres' expertise. However, one important and often under rated factor is patient-related factors. There is considerable evidence that patients and physicians have different goals for treatment and physicians' understanding of their own patients' preferences is not accurate. Several patient-related key factors have been identified such as age, religious beliefs, sexual health, educational background, and cognitive impairment. We have focused on these areas and highlight some key factors that need to be taken considered whilst counselling a patient and understanding his choice of treatment, which might not always be match with the clinicians' recommendation.

Multiparametric MRI identifies and stratifies prostate cancer lesions: implications for targeting intraprostatic targets.

PURPOSE: To assess the ability of multiparametric (mp) MRI (mp-MRI) to identify, stratify, and localize biopsy-proven prostate cancer lesions in a risk-stratified patient population. METHODS AND MATERIALS: We retrospectively analyzed 57 patients who had mp-MRI and core needle biopsy during diagnostic prostate cancer evaluation. The MRI sequences were scored for suspicion of cancer with a previously described system. Distributions of mp-MRI scores were compared across National Comprehensive Cancer Network prostate cancer risk groups. The mp-MRI-identified lesions were compared with the location of positive core needle biopsies to assess mp-MRI localization of true lesions. RESULTS: The mp-MRI scoring system identified lesions in 84% (48/57) of the patients, including 100% (12/12) in the high-risk group. Scores assigned to lesions in patients in intermediate- and high-risk groups were statistically higher than those in the low-risk group, with a relative risk of 6.72 (95% confidence interval: 2.32-19.51, p<0.001) of having an aggressive score assigned in high-risk patients compared with the low-risk patients. In comparing the localization data from core needle biopsy, 68% of the patients had an MRI-identified lesion in or within one adjacent sextant of the same prostate hemigland, including 85% of aggressive lesions. CONCLUSIONS: Use of mp-MRI at the time of diagnosis can identify intraprostatic lesions and assign suspicion for high-risk disease. These data show that high-risk patients are more likely to have suspicious imaging-identified lesions that correlate to the location of biopsy-proven prostate cancer. At this time, the use of mp-MRI to define focal targets represents a complementary tool to patient evaluation for focal therapy strategies.