Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS: Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. These included the development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS: The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS: The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

Clinical impact of Prostate-Specific Membrane Antigen Positron Emission Tomography (PET) on intensification or deintensification of advanced renal cell carcinoma management.

PURPOSE: There is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment.

Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?

OBJECTIVE: To provide a summary and discussion of international guidelines, position statements and consensus statements in relation to focal therapy (FT) for prostate cancer (PCa). METHODS: The European Association of Urology-European Association of Nuclear Medicine-European Society for Radiotherapy and Oncology-European Society of Urogential Radiology-International Society of Urological Pathology-International Society of Geriatric Oncology and American Urological Association-American Society for Radiation Oncology-Society of Urologic Oncology guidelines were interrogated for recommendations for FT. PubMed and Ovid Medline were searched for consensus statements. Only studies in English since 2015 were included. Reference lists of the included articles were also interrogated and a manual search for studies was also performed. RESULTS: Our results showed a lack of long-term randomised data for FT. International Urological guidelines emphasised the need for more high-quality clinical trials with robust oncological and toxicity outcomes. Consensus and positions statements were heterogenous. CONCLUSION: A globally accepted guideline for FT planning, technique and follow-up are still yet to be determined. Well-designed studies with long-term follow-up and robust clinical and toxicity endpoints are needed to improve our understanding of FT and create uniform guidelines to streamline management and follow-up.

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin.

BACKGROUND: Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized. OBJECTIVE: To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers. DESIGN, SETTING, AND PARTICIPANTS: In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis. RESULTS: In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2-ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549-BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden. CONCLUSIONS: Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.

Primary tumour PSMA intensity is an independent prognostic biomarker for biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: The prognostic value of PSMA intensity on PSMA PET/CT due to underlying biology and subsequent clinical implications is an emerging topic of interest. We sought to investigate whether primary tumour PSMA PET intensity contributes to pre- and post-operative prediction of oncological outcomes following radical prostatectomy. METHODS: We performed a retrospective cohort study of 848 men who underwent all of multiparametric MRI (mpMRI), transperineal prostate biopsy, and 68 Ga-PSMA PET/CT prior to radical prostatectomy. PSMA intensity, quantified as maximum standard uptake value (SUVmax), and other clinical variables were considered relative to post-operative biochemical recurrence-free survival (BRFS) using Cox regression and Kaplan-Meier analysis. RESULTS: After a median follow-up of 41 months, 219 events occurred; the estimated 3-year BRFS was 79% and the 5-year BRFS was 70%. Increasing PSMA intensity was associated with less favourable BRFS overall (Log rank p < 0.001), and within subgroups of Gleason score category (Log rank p < 0.03). PSMA intensity was significantly associated with shorter time to biochemical recurrence, after adjusting for pre-operative (HR per 5-unit SUVmax increase = 1.15) and post-operative (HR per 5-unit SUVmax increase = 1.10) parameters. CONCLUSION: These results in a large series of patients confirm PSMA intensity to be a novel, independent prognostic factor for BRFS.

Oncological and urinary outcomes following low-dose-rate brachytherapy with a median follow-up of 11.8 years.

OBJECTIVES: To examine the long-term oncological outcomes and urological morbidity of low-dose-rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate-risk prostate cancer. PATIENTS AND METHODS: A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side-effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate-specific antigen (PSA) level of ≥0.2 µg/L. RESULTS: Minimum patient follow-up was 5.5 years. The median follow-up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9-17) µg/L and the median Gleason score was 3 + 4. The biochemical relapse-free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a 'surgical' definition of a PSA level of <0.2 µg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer-specific survival (PCSS) was 98% (291/297). Post-LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow-up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT. CONCLUSION: LDRBT is associated with excellent PCSS, with a median follow-up of 11.8 years. The risk of post-implantation urethral stricture and UI is low and a pre-implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture.

68Ga-PSMA PET/CT tumour intensity pre-operatively predicts adverse pathological outcomes and progression-free survival in localised prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy. METHODS: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis. RESULTS: 68Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4-48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity. CONCLUSION: Intraprostatic 68Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.

Histological comparison between predictive value of preoperative 3-T multiparametric MRI and 68 Ga-PSMA PET/CT scan for pathological outcomes at radical prostatectomy and pelvic lymph node dissection for prostate cancer.

OBJECTIVE: To evaluate the ability of preoperative multiparametric magnetic resonance imaging (mpMRI) and a gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) scan to predict pathological outcomes and also identify a group of men with a <5% risk of histological pelvic lymph node metastasis (LNM) at pelvic lymph node dissection (PLND) performed during a robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer. We then aimed to compare these results to known risk calculators for LNM, including the Cancer of the Prostate Risk Assessment (CAPRA) score, Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti nomograms. PATIENTS AND METHODS: Between July 2014 and September 2019 only men who had both a preoperative mpMRI and staging 68 Ga-PSMA PET/CT at our institution followed by a RALP with PLND referred to a single specialist uropathology laboratory were considered for inclusion. The data were collected retrospectively prior to February 2019 and in a prospective manner thereafter. A model was built to allocate probabilities of the men with a negative 68 Ga-PSMA PET/CT scan having a <5% risk of histologically LNM at RALP based on the preoperative radiological staging. RESULTS: A total of 233 consecutive men met the inclusion criteria of which 58 men (24.9%) had a LNM identified on PLND histology. The median (range) International Society of Urological Pathology (ISUP) Grade was 5 (1-5) and the median (range) prostate-specific antigen level was 7.4 (1.5-72) ng/mL. The median (range) number of resected lymph nodes was 16 (1-53) and the median (range) number of positive nodes identified on histology was 2 (1-22). Seminal vesicle invasion on mpMRI was more common in node-positive men than in the absence of LNM (31% vs 12%). The maximum standardised uptake value of the primary tumour on 68 Ga-PSMA PET/CT was higher in men with LNM (median 9.2 vs 7.2, P = 0.02). Suspected LNM were identified in 42/233 (18.0%) men with 68 Ga-PSMA PET/CT compared with 22/233 (9.4%) men with mpMRI (P = 0.023). The positive and negative predictive value for 68 Ga-PSMA PET/CT was 66.7% and 84.3% respectively, compared to 59.1% and 78.7% for mpMRI. A predictive model showed only two men (4.2%) with a negative preoperative 68 Ga-PSMA PET/CT would be positive for a histological LNM if they are ISUP Grade < 5 and Prostate Imaging-Reporting and Data System (PI-RADS) <5; or ISUP Grade 5 with PI-RADS < 4. An inspection of three additional variables: CAPRA score, MSKCC and Briganti nomograms did not improve the predictive probability for this group. However, of the 61 men with ISUP Grade 4-5 malignancy and also a PI-RADS 5 mpMRI, 20 (32.8%) men had a microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT. CONCLUSION: Preoperative 68 Ga-PSMA/PET CT was more sensitive in identifying histological pelvic LNM than 3-T mpMRI. Men with a negative 68 Ga-PSMA PET/CT have a lower risk of LNM than predicted with CAPRA scores or MSKCC and Briganti nomograms. We identified that the combination of a negative preoperative 68 Ga-PSMA PET/CT, ISUP biopsy Grade <5 and PI-RADS <5 prostate mpMRI, or an ISUP Grade 5 with PI-RADS <4 on mpMRI was associated with a <5% risk of a LNM. The addition of CAPRA scores, MSKCC and Briganti nomograms did not improve the predictive probability within this model. Conversely, men with ISUP Grade 4-5 malignancy associated with a PI-RADS 5 prostate mpMRI had a >30% risk of microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT and this high-risk group would appear suitable for an extended PLND at the time of a radical prostatectomy.

68Ga-PSMA PET/CT better characterises localised prostate cancer after MRI and transperineal prostate biopsy: Is 68Ga-PSMA PET/CT guided biopsy the future?

BACKGROUND: 68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear. METHODS: Retrospective analysis of patients undergoing mpMRI, prostate biopsy and 68Ga-PSMA PET/CT over a 3-year period. Diagnostic performance of 68Ga-PSMA PET/CT and mpMRI were assessed using biopsy histopathology for the entire cohort and radical prostatectomy specimen in a subset of patients. Lesion concordance and additional detection of each modality were determined, including in a dedicated cohort of patients with mpMRI PIRADS 2 scans. RESULTS: A total of 144 patients were included in the study. Index lesion/foci detection was similar between 68Ga-PSMA PET/CT and mpMRI (sensitivity 83.1% vs 90.1%; p = 0.267), however lesions missed by mpMRI were larger (1.66 cm3 vs 0.72 cm3; p = 0.034). Lesion detection rates were similar across the biopsy histopathology and radical prostatectomy specimen subset, with a high concordance for index (80.1%) and a moderate concordance for total (67%) lesions between the 2 imaging modalities. The additional detection yield favoured 68Ga-PSMA PET/CT over mpMRI for index (13.5% vs 4.3%) and total (18.2% vs 5.4%) lesions; both modalities missed 2.1% and 12.3% of index and total lesions, respectively. 68Ga-PSMA PET/CT identified 9 of 11 patients with PIRADS 2 mpMRI but subsequently diagnosed with Gleason ≥ 3 + 4 disease. CONCLUSIONS: Despite high concordance rates, 68Ga-PSMA PET/CT incrementally improved tumour localisation compared with mpMRI. These results suggest that 68Ga-PSMA PET/CT may have an incremental value to that of mpMRI in the diagnostic process for prostate.

Use of a trizonal schema to assess targeting accuracy in prostatic fusion biopsy.

OBJECTIVES: To describe the use of a novel 'trizonal' biopsy schema in which 'near-target' biopsies are taken adjacent to the MRI lesion, in addition to target and systematic biopsies, to determine the accuracy of prostate MRI fusion systems. PARTICIPANTS AND METHODS: A trizonal biopsy technique was used to evaluate 75 men with small Prostate Imaging Reporting and Data System (PI-RADS) 3-5 MRI lesions (<15 mm) identified from a prospective cohort of 290 men undergoing multiparametric magnetic resonance imaging (MRI) for suspected prostate cancer at a single high-volume institution between September 2017 and May 2019. In addition to target and systematic biopsies, near-target biopsies were taken 4 mm from the apparent border of the MRI lesion. Comparisons were made between highest International Society of Urological Pathology grade and longest tumour length. RESULTS: Fifty-three men with significant prostate cancer in the same quadrant as the target were included in the final analysis. The percentages of positive cores from target, near-target and MRI-negative zones were 66%, 39% and 17%, respectively. Significant cancer was detected in the near-target zone in 77% of cases when the target zone was positive. A total of 17% of participants were upgraded by a median (range) of 1 (1-3) grades through the addition of near-target cores. Notably, 9% of men were diagnosed with clinically significant prostate cancer solely via the near-target biopsy cores when the target cores were negative. CONCLUSION: The use of near-target biopsies as part of a trizonal biopsy schema provides a novel methodology to optimize clinically significant prostate cancer detection.

Solitary rib lesions showing prostate-specific membrane antigen (PSMA) uptake in pre-treatment staging 68 Ga-PSMA-11 positron emission tomography scans for men with prostate cancer: benign or malignant?

OBJECTIVES: To determine the proportion of solitary rib lesions on pre-treatment 68 Gallium-labelled prostate-specific membrane antigen (PSMA)/computed tomography (CT) scans in men with prostate cancer that are malignant and examine any predictive factors. PATIENTS AND METHODS: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68 Ga-PSMA-11 positron emission tomography (PET)/CT scans performed for primary staging prior to treatment of prostate cancer from July 2014 to September 2019. Men with PSMA uptake outside the prostate in only the rib lesion were included. A solitary rib lesion was considered to be malignant if it increased in size on follow-up imaging. A lesion was considered benign if the prostate-specific antigen (PSA) level remained <0.1 µg/L following a radical prostatectomy (RP), <2 µg/L above nadir following radiotherapy (RT) as per the Phoenix criteria, histology was benign on rib biopsy, or follow-up imaging showed no growth of the rib lesion. If a lesion did not meet these criteria it was considered indeterminate. RESULTS: A total of 62 men had PSMA uptake in a solitary rib lesion; 54 went on to have RPs and eight underwent RT. In all, 61 of the men (98.4%) met the criteria for a benign rib lesion. Only one man had a false-negative malignant lesion. This man had a rib lesion with a low maximum standardised uptake value (SUVmax ) of 2.21 reported as benign, but the postoperative PSA level was 0.67 µg/L and the rib lesion progressed on follow-up imaging, with development of widespread metastases. Of the benign rib lesions, there were four false positives reported as possible metastases. Three had percutaneous rib biopsies, two of which came back with benign histology and one was indeterminate. The indeterminate biopsy patient had a RP and his postoperative PSA level was <0.1 µg/L. A total of 43 (69.4%) men with benign rib lesions had a SUVmax greater than the SUVmax of the malignant lesion. CONCLUSION: To our knowledge, this is the first cohort study of men with PSMA-avid solitary rib lesions on pre-treatment 68 Ga-PSMA PET/CT staging scans for prostate cancer. Our results indicate that the vast majority of these lesions have low-intensity uptake and are benign. Intervention to confirm this is not usually required.

Management of benign prostatic hyperplasia in the 21st century: temporal trends in Australian population-based data.

OBJECTIVE: To examine national trends in the medical and surgical treatment of benign prostatic hyperplasia (BPH) using Australian Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) population data from 2000 to 2018. PATIENTS AND METHODS: Annual data was extracted from the MBS, PBS and Australian Institute of Health and Welfare databases for the years 2000-2018. Population-adjusted rates of BPH procedures and medical therapies were calculated and compared in relation to age. Cost analysis was performed to estimate financial burden due to BPH. RESULTS: Overall national hospital admissions due to BPH declined between 2000 and 2018, despite an increased proportion of admissions due to private procedures (42% vs 77%). Longitudinal trends in the medical management of BPH showed an increased prescription rate of dutasteride/tamsulosin combined therapy (111 vs 7649 per 100 000 men) and dutasteride monotherapy (149 vs 336 per 100 000 men) since their introduction to the PBS in 2011. Trends in BPH surgery showed an overall progressive increase in rate of total procedures between 2000 and 2018 (92 vs 133 per 100 000 men). Transurethral resection of the prostate (TURP) remained the most commonly performed surgical procedure, despite reduced utilisation since 2009 (118 vs 89 per 100 000 men), offset by a higher uptake of photoselective vaporisation of prostate, holmium:YAG laser enucleation of prostate, and later likely due to minimally invasive surgical therapies including prostatic urethral lift and ablative technologies (including Rezum™). Financial burden due to BPH surgery has remained steady since 2009, whilst the burden due to medical therapy has risen sharply. CONCLUSION: Despite reduced national BPH-related hospitalisations, overall treatment for BPH has increased due to medical therapy and surgical alternatives to TURP. Further exploration into motivators for particular therapies and effect of medical therapy on BPH progression in clinical practice outside of clinical trials is warranted.

Improved detection and reduced biopsies: the effect of a multiparametric magnetic resonance imaging-based triage prostate cancer pathway in a public teaching hospital.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves clinically significant prostate cancer (csPCa) detection by facilitating targeted biopsy (cognitive, fusion technology, or in-gantry MRI guidance) and reducing negative biopsies. This study sought to describe the feasibility of introducing an mpMRI-based triage pathway, including diagnostic performance, applicability to training, and cost analysis. METHODS: An observational retrospective cohort study of consecutive patients attending a large public tertiary referral training hospital who underwent mpMRI for suspicion of prostate cancer was considered. Standard clinical, MRI-related, histopathological, and financial parameters were collected for analysis of biopsy avoidance, diagnostic accuracy of biopsy approach, and operator (consultant and resident/registrar) and logistical (including financial) feasibility. RESULTS: 653 men underwent mpMRI, of which 344 underwent prostate biopsy resulting in a 47% biopsy avoidance rate. Overall, 240 (69.8%) patients were diagnosed with PCa, of which 208 (60.5%) were clinically significant, with higher rates of csPCa observed for higher PIRADS scores. In patients who underwent both systematic and targeted biopsy (stTPB), targeted cores detected csPCa in 12.7% and 16.6% in more men than systematic cores in PIRADS 5 and 4, respectively, whereas systematic cores detected csPCa in 5% and 3.2% of patients, where targeted cores did not. A high standard of performance was maintained across the study period and the approach was shown to be cost effective. CONCLUSIONS: Introdution of an mpMRI-based triage system into a large public tertiary teaching hospital is feasible, cost effective and leads to high rates of prostate cancer diagnosis while reducing unnecessary biopsies and detection of insignificant PCa.

Understanding the diagnosis of prostate cancer.

Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men. Prostate-specific antigen testing is personalised (not dichotomous in nature) and its interpretation should take into account the patient's age, symptoms, previous results and medication (eg, 5-α reductase inhibitors such as dutasteride). Multiparametric magnetic resonance imaging of the prostate has been proven to have a 93% sensitivity for detecting clinically significant prostate cancer. It has the potential to decrease unnecessary prostate biopsies by around 27%. International Society of Urological Pathology (ISUP) grade 1 (Gleason score 6) has been shown to have very little, if any, risk of metastasis ISUP grade 1 (Gleason score 3 +3 = 6) and low percentage ISUP grade 2 (Gleason score 3 + 4 [< 10%] = 7) can be offered active surveillance. The goal of active surveillance is to defer treatment but is still curative when required. With better imaging (magnetic resonance imaging and emerging prostate-specific membrane antigen positron emission tomography-computed tomography) and transperineal prostate biopsy, more men can be offered screening after discussion of risks and benefits, knowing that overdiagnosis has been minimised and radical treatment is reserved for only the most aggressive disease.

Outcomes of Primary Lymph Node Staging of Intermediate and High Risk Prostate Cancer with 68Ga-PSMA Positron Emission Tomography/Computerized Tomography Compared to Histological Correlation of Pelvic Lymph Node Pathology.

PURPOSE: The majority of men who undergo pelvic lymph node dissection at radical prostatectomy have benign lymph node histology. The aim of this study was to assess the predictive value of preoperative 68Ga-PSMA (prostate specific membrane antigen) positron emission tomography/computerized tomography to predict histological metastasis on pelvic lymph node dissection performed during radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the sensitivity, specificity, and positive and negative predictive values of preoperative staging 68Ga-PSMA positron emission tomography/computerized tomography to identify histological lymph node metastasis in 208 consecutive men who subsequently proceeded with pelvic lymph node dissection at radical prostatectomy. RESULTS: Median prostate specific antigen was 7.6 µg/l, the lymph node count was 13 and Gleason score was 4 + 5. On a per patient basis only 21 of the 55 men with metastasis on histological examination were identified on 68Ga-PSMA positron emission tomography/computerized tomography for 38.2% sensitivity. Of the 143 men with no lymph node metastasis on 68Ga-PSMA imaging 34 had metastasis on histology for 80.8% negative predictive value. Specificity was 93.5% and positive predictive value was 67.7%. For the 172 histologically identified malignant lymph node metastases the sensitivity per node was 24.4% and specificity was 99.5%. CONCLUSIONS: If negative 68Ga-PSMA positron emission tomography/computerized tomography is used as the basis of not performing pelvic lymph node dissection, 80% of men would avoid unnecessary pelvic lymph node dissection. However, 68Ga-PSMA positron emission tomography/computerized tomography has poor sensitivity per node to detect all histologically positive lymph node metastases. Thus, pelvic lymph node dissection remains the gold standard to stage pelvic lymph nodes despite its known limitations and complications.

The use of 68Ga-PET/CT PSMA in the staging of primary and suspected recurrent renal cell carcinoma.

PURPOSE: The role of 68Ga-PSMA PET/CT in the staging of prostate cancer is well known. PSMA is also overexpressed in the neovasculature of other tumours including renal cell carcinoma (RCC), suggesting there may be a role for the use of 68Ga-PSMA PET/CT. Thus far, there has been limited literature documenting the use of 68Ga-PSMA PET/CT in the investigation and management decisions of RCC. METHODS: This was a retrospective case series of patients who received a 68Ga-PSMA PET/CT scan for staging or restaging of RCC between July 2016 and December 2018. Primary outcome measure was to identify whether 68Ga-PSMA PET/CT changed management compared to standard diagnostic CT imaging. Analysis was based on four categories: (1) identification of new disease, (2) refuting disease on CT imaging, (3) identification of synchronous primaries, and (4) concordance with CT imaging. RESULTS: 38 68Ga-PSMA PET/CT scans met inclusion criteria. Primary staging scans were performed in 16 patients, of which 75% showed avid primary lesions, with the majority of clear cell subtype. Management was changed in 43.8% of patients. CT agreed with 68Ga-PSMA PET/CT in 37.5% of cases. Restaging scans were performed in 22 patients. 40.9% of patients had management changed by results of 68Ga- PSMA PET/CT. CT agreed with 68Ga- PSMA PET/CT in 36.4% of cases. Management was predominantly changed due to the identification of new sites of suspected metastases, as well as the detection of synchronous primaries. CONCLUSIONS: 68Ga-PSMA PET/CT directly changed management in 42.1% of cases. Strongest detection rates occurred in those patients with clear cell RCC. The results of this study suggest there may be merit in the use of the modality in the staging of RCC. Further analysis, both with respect to histological confirmation, efficacy and cost-benefit, is required to determine whether there is a role for routine 68Ga-PSMA PET/CT imaging.

Improved specificity with 68Ga PSMA PET/CT to detect clinically significant lesions "invisible" on multiparametric MRI of the prostate: a single institution comparative analysis with radical prostatectomy histology.

PURPOSE: Positron emission tomography (PET) for prostate-specific membrane antigen (PSMA) represents a promising method for prostate cancer diagnosis and staging. Comparisons of PSMA-based tumour characterisation to multiparametric MRI (mpMRI) are limited, hence this study sought to compare the diagnostic accuracy of 68Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland histopathology. METHODS: A retrospective cohort study of consecutive patients who underwent pre-operative mpMRI and 68Ga-PSMA PET/CT followed by a RP was performed. Standard clinical parameters were collected. "Per patient" and "per lesion" analyses for image-based detection according to RP histopathology were described using sensitivity, specificity and other measures of diagnostic accuracy. RESULTS: Fifty-eight patients (median age 65.5 years, median PSA 7.35 ng/mL) underwent RP, resulting in a high-risk cohort (≥pT3 69%). Sensitivities for identification of index lesion, bilateral and multifocal disease were 90%, 21%, 19% for mpMRI and 93%, 42%, 34% for 68Ga-PSMA PET/CT. Histology analyses revealed 88 cancer foci of Gleason grades 3 + 3 (4%), 3 + 4 (64%), 4 + 3 (19%), 4 + 4 (3%) and ≥ 4 + 5 (10%), of which 68Ga-PSMA PET/CT correctly detected more foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729). CONCLUSIONS: 68Ga-PSMA PET/CT may better reflect RP histopathology compared to mpMRI when considering multifocal and bilateral disease. These findings may influence surgical planning, targeted biopsy and focal therapy strategies and require further research.

Risk of metastatic disease on 68 gallium-prostate-specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer.

OBJECTIVE: To determine the number of men with 68 gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) avid metastasis at diagnosis, as most data on 68 Ga-PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with 68 Ga-PSMA PET/CT. PATIENTS AND METHODS: A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for 68 Ga-PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018. The primary outcome measure was to determine the risk of metastasis based on 68 Ga-PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) level, and staging with pre-biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results. RESULTS: The median PSA level was 6.5 ng/mL and median ISUP grade was 3, with high-risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of <10 ng/mL and 43% with a PSA level of >20 ng/mL. Metastases were identified in 6.4% with ISUP grade 2-3 and 21% with ISUP grade 4-5. Pre-biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate-risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high-risk disease. CONCLUSIONS: These results support the use of 68 Ga-PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis.

MRI-guided in-bore biopsy for prostate cancer: what does the evidence say? A case series of 554 patients and a review of the current literature.

PURPOSE: To review our experience with MRI-guided in-bore prostate biopsy (MRGB) and present a review of the literature on MRGB. METHODS: A retrospective review of patients presenting for MRGB between 2013 and 2018. Diagnostic and biopsy MRI scans were reviewed to collect data on scan dates, procedure times, characteristics of MRI targets (PI-RADS™ score, target size, ADC value and location). A review of the literature on MRGB for the period 2013-2018 was performed. RESULTS: 607 targets in 554 men were biopsied. Overall and significant cancer detection rate were 80% and 55% at a patient level, and 76 and 59% at the target level, respectively. Prostate cancer (CaP) detection in men with prior negative biopsy was 60% while 50% of men on active surveillance were upgraded to clinically significant disease (CSD). Lesion location did not predict for presence of CaP or CSD. PI-RADS™ score, age and PSAD were predictors of CSD at biopsy on multivariate analysis. Literature review identified 23 reports reporting on MRGB cohorts (~ 4000 patients). Overall cancer detection ranged from 23 to 74% and CSD in 63% overall. CaP detection in PI-RADS™ 3 targets was substantially lower in our series and the literature than for PI-RADS™ 4-5 targets. CONCLUSIONS: MRGB in PI-RADS™ 3-5 targets yields high rates of cancer diagnosis. High detection rates are also seen in men with prior negative biopsy and AS cohorts. PI-RADS™ score, age and PSAD can reliably predict CSD detection. The number of published series is small and the role of MRGB in PI-RADS™ 3 targets needs further study.