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.

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.

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.

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.

A prospective study of psychological distress after prostate cancer surgery.

BACKGROUND: Men treated for prostate cancer experience heightened psychological distress and have an increased risk of suicide. Management of this distress and risk is crucial for quality urological care. OBJECTIVE: To identify risk indicators for poorer trajectories of psychological adjustment and health-related quality of life (QoL) after surgery for localised prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Patients were newly diagnosed with localised prostate cancer scheduled for surgical treatment. Patients were assessed at baseline (pre-surgery) and 6 weeks, 3 months, 6 months, 12 months, and 24 months post-surgery. MEASUREMENTS: Assessment measures included sociodemographics, domain-specific and health-related QoL, and psychological distress. Mixed effects regression models were used to analyse the data. RESULTS AND LIMITATIONS: A total of 233 patients provided data for this analysis (Mage = 60 years, standard deviation [SD] = 4.02; MPSA = 7.37 ng/mL). At baseline, the prevalence of high psychological distress was 28% reducing to 21% at 24 months. Before treatment, younger age, more comorbidities, and worse bowel function were related to greater psychological distress; and younger age and better urinary, sexual, and bowel function were related to better health-related QoL. By contrast, for changes over time, only bowel function was important with better bowel function predicting decreasing psychological distress for men. CONCLUSIONS: Regular distress screening is indicated over the 24 months after surgery for localised prostate cancer. Care pathways for men with prostate cancer need also to respond to age-specific concerns and health problems associated with comorbidities in aging men. Focussed symptom control for bowel bother should be a priority.

Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: 24-month outcomes from a randomised controlled study.

BACKGROUND: Previous trials have found similar early outcomes after robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy. We report functional and oncological postoperative outcomes up to 24 months after surgery for these two surgical techniques. METHODS: In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women's Hospital (Brisbane, QLD, Australia). Participants were randomly assigned (1:1) to have either robot-assisted laparoscopic prostatectomy or open radical retropubic prostatectomy. Randomisation was computer generated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patient's surgical treatment. Primary outcomes were urinary function (urinary domain of Expanded Prostate Cancer Index Composite [EPIC]) and sexual function (sexual domain of EPIC and International Index of Erectile Function Questionnaire [IIEF]) at 6 months, 12 months, and 24 months and oncological outcome (biochemical recurrence and imaging evidence of progression). The trial was powered to assess health-related and domain-specific quality-of-life outcomes over 24 months. All analyses were done on a per-protocol basis. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000661976. FINDINGS: Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to robot-assisted laparoscopic prostatectomy and 163 to open radical retropubic prostatectomy. 18 withdrew (12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group and 157 in the robot-assisted laparoscopic prostatectomy group proceeded to surgery. At the 24-month follow-up time point, 150 men remained in the robot-assisted laparoscopic prostatectomy group and 146 remained in the open radical retropubic prostatectomy group. Urinary function scores did not differ significantly between robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy at 6 months post-surgery (88·68 [95% CI 86·79-90·58] vs 88·45 [86·54-90·36]; p1<0·0001, p2<0·0001), 12 months post-surgery (90·76 [88·89-92·62] vs 91·53 [90·07-92·98]; p1<0·0001, p2<0·0001), or 24 months post-surgery (91·33 [89·64-93·03] vs 90·86 [89·01-92·70]; p1<0·0001, p2<0·0001). Sexual function scores were not significantly different between robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy at 6 months post-surgery (EPIC: 37·40 [33·60-41·19] vs 38·63 [34·76-42·49], p1=0·0001, p2<0·0001; IIEF: 29·75 [26·66-32·84] vs 29·78 [26·41-33·16], p1<0·0001, p2<0·0001), 12 months post-surgery (EPIC: 42·28 [38·05-46·51] vs 42·51 [38·29-46·72], p1<0·0001, p2<0·0001; IIEF: 33·10 [29·59-36·61] vs 33·50 [29·87-37·13], p1=0·0002, p2<0·0001), or 24 months post-surgery (EPIC: 45·70 [41·17-50·23] vs 46·90 [42·20-51·60], p1=0·0003, p2<0·0001; IIEF: 33·95 [30·11-37·78] vs 33·89 [29·82-37·96], p1=0·0003, p2=0·0004). Equivalence testing on the difference between the proportion of biochemical recurrences between the two groups (13 [9%] in the open radical retropubic prostatectomy group vs four [3%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a prespecified margin of 10%. However, a superiority test showed that the two proportions were significantly different (p=0·0199). Equivalence testing on the proportion of patients who had imaging evidence of progression revealed that the two groups were not significantly different (p=0·2956). INTERPRETATION: Robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy yielded similar functional outcomes at 24 months. We advise caution in interpreting the oncological outcomes of our study because of the absence of standardisation in postoperative management between the two trial groups and the use of additional cancer treatments. Clinicians and patients should view the benefits of a robotic approach as being largely related to its minimally invasive nature. FUNDING: Cancer Council Queensland.

Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study.

BACKGROUND: The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology. We aimed to compare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks. METHOD: In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, were able to read and speak English, had no previous history of head injury, dementia, or psychiatric illness or no other concurrent cancer, had an estimated life expectancy of 10 years or more, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women's Hospital (Brisbane, QLD). Participants were randomly assigned (1:1) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy. Randomisation was computer generated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patient's condition. Further, a masked central pathologist reviewed the biopsy and radical prostatectomy specimens. Primary outcomes were urinary function (urinary domain of EPIC) and sexual function (sexual domain of EPIC and IIEF) at 6 weeks, 12 weeks, and 24 months and oncological outcome (positive surgical margin status and biochemical and imaging evidence of progression at 24 months). The trial was powered to assess health-related and domain-specific quality of life outcomes over 24 months. We report here the early outcomes at 6 weeks and 12 weeks. The per-protocol populations were included in the primary and safety analyses. This trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12611000661976. FINDINGS: Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to radical retropubic prostatectomy and 163 to robot-assisted laparoscopic prostatectomy. 18 withdrew (12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group. 121 assigned to radical retropubic prostatectomy completed the 12 week questionnaire versus 131 assigned to robot-assisted laparoscopic prostatectomy. Urinary function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (74·50 vs 71·10; p=0·09) or 12 weeks post-surgery (83·80 vs 82·50; p=0·48). Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (30·70 vs 32·70; p=0·45) or 12 weeks post-surgery (35·00 vs 38·90; p=0·18). Equivalence testing on the difference between the proportion of positive surgical margins between the two groups (15 [10%] in the radical retropubic prostatectomy group vs 23 [15%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a Δ of 10%. However, a superiority test showed that the two proportions were not significantly different (p=0·21). 14 patients (9%) in the radical retropubic prostatectomy group versus six (4%) in the robot-assisted laparoscopic prostatectomy group had postoperative complications (p=0·052). 12 (8%) men receiving radical retropubic prostatectomy and three (2%) men receiving robot-assisted laparoscopic prostatectomy experienced intraoperative adverse events. INTERPRETATION: These two techniques yield similar functional outcomes at 12 weeks. Longer term follow-up is needed. In the interim, we encourage patients to choose an experienced surgeon they trust and with whom they have rapport, rather than a specific surgical approach. FUNDING: Cancer Council Queensland.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

OBJECTIVE: To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. METHODS: This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. RESULTS: There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. CONCLUSION: We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality.

Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years.

OBJECTIVE: To evaluate the long-term outcomes of high-dose-rate (HDR) brachytherapy for patients with intermediate- and high-risk prostate cancer. SUBJECTS AND METHODS: We retrospectively analysed a prospective longitudinal cohort database including a single-surgeon series of 507 consecutive men treated with external beam radiotherapy and an HDR prostate brachytherapy boost between August 2000 and December 2009. The risk factors used were based on the D'Amico classification. We measured the incidence of no biochemical evidence of disease (bNED) based on the Phoenix definition of failure (nadir PSA + 2 ng/mL). We also reviewed the incidence of urethral stricture in this cohort. RESULTS: With minimum and median follow-ups of 6 and 10.3 years, respectively, the bNED rates for men with intermediate- and high risk disease were 93.3% and 74.2%, respectively, at 5 years and 86.9% and 56.1%, respectively, at 10 years. The 10-year bNED rate for men with only one intermediate-risk factor was 94%, whereas for patients with all three high-risk factors it was 39.5%. The overall urethral stricture rate was 13.6%. Before 2005, the urethral stricture rate was 28.9% and after January 2005 it was 4.2%. For the 271 men with a minimum follow-up of 10 years the actuarial 10-year prostate cancer-specific survival rate was 90.8% and the actuarial overall survival rate was 86.7%. CONCLUSIONS: For men with intermediate- or high-risk prostate cancer features, who are considered not suitable for, or wish to avoid a radical prostatectomy, HDR prostate brachytherapy remains an appropriate treatment option. From December 2004, prevention strategies decreased the risk of post-brachytherapy urethral strictures.

The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology: A single centre retrospective study.

Objective: To review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. Methods: Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. Results: Three percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). Conclusion: In this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

The Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Primary Staging of Selected Renal Tumours: Initial Experience in a Multicentre Cohort.

BACKGROUND: Accurate primary staging of renal cancer with conventional imaging is challenging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) may serve to improve the accuracy of renal cancer staging. OBJECTIVE: To determine clinicopathological and management differences for primary renal cancer staged with PSMA PET/CT in comparison to conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of PSMA PET/CT scans performed for primary staging of renal cancer and incidental renal lesions at three sites in Brisbane, Australia between June 2015 and June 2020. Clinical characteristics, imaging, and histopathology were reviewed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinicopathological and management differences according to staging modality (PSMA PET/CT, conventional imaging) were assessed. Descriptive statistics were used to report demographics and clinical parameters. Nonparametric methods were used for statistical analysis. Fisher's exact test was used for comparison of small-cell size categorical variables. RESULTS AND LIMITATIONS: From a total of 120 PSMA PET/CT scans, 61 were included (52 staging, 9 incidental) for predominantly males (74%) with a mean age of 65.1 yr (standard deviation 12.0). Most primary lesions (40/51) were clear-cell renal cell carcinoma (ccRCC; 98% PSMA-avid), eight were non-ccRCC (75% PSMA-avid), and three were non-RCC (oncocytoma; 67% PSMA-avid). PSMA PET identified a greater number of presumed metastatic lesions than conventional imaging (195 vs 160). A management change was observed for 32% of patients (20% major, 12% minor). Limitations include the retrospective design and selection bias, lack of blinding to PSMA reporting, and the use of different PSMA radiotracers. CONCLUSIONS: PSMA PET/CT detected more metastases than conventional imaging and most renal cancers were PSMA-avid, resulting in a management change for one-third of the patients. PATIENT SUMMARY: We looked at a newer type of scan called PSMA PET/CT for first staging of kidney cancer. We found that this detects more metastasis and helps in decisions on changes in treatment for some patients. This type of imaging is a useful addition to conventional scans in tricky cases and may help in better selection of suitable treatments, but more studies are required.

Clinicopathologic Significance of Anterior Prostate Cancer: Comparison With Posterior Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging.

Anterior prostate cancer (APC) has been considered an indolent tumor, most commonly arising in the transition zone (TZ). More recently, detection of APC has been facilitated through multiparametric magnetic resonance imaging and improved biopsy techniques, enabling earlier detection. The pathologic features and clinical significance of pure APC in a large contemporary series of well-characterized tumors have, to date, not been elucidated. Cases with APC defined as cancer present anterior to the urethra only were identified from 1761 consecutive radical prostatectomy specimens accessioned between January 2015 and August 2016. The clinicopathologic features of these cases were compared with those of pure posterior prostate cancer (PPC) and the features of anterior peripheral zone (APZ) cancers were compared with those of TZ cancers. In addition, the tumor series from 2015 to 2016 was compared with a cohort of 1054 patients accessioned before the utilization of multiparametric magnetic resonance imaging in the routine workup of patients with prostate cancer. In the 2015-2016 series, there were 188 (10.7%) patients with APC compared with 5.4% in the series from the pre-multiparametric magnetic resonance imaging era. No difference was observed between APC and PPC with regards to patient age or mean serum prostate-specific antigen at presentation. Mean tumor volume and positive surgical margin (PSM) rates were significantly higher in APC. In contrast, PPC was more commonly high grade with more frequent extraprostatic extension (EPE). None of the cases of APC had infiltration of the seminal vesicle or lymph node involvement, in contrast to PPC, with almost 14% of cases in each category. The 3- and 5-year biochemical recurrence-free survival was significantly higher in APC when compared with PPC, although this was not retained on multivariable analysis which included tumor location. On division of APCs according to anatomic zone of origin, 45% were APZ cancer and 37% TZ cancer. On comparison of APZ and TZ cancers, there were no significant differences in mean age and serum prostate-specific antigen at presentation as well as tumor volume, Gleason score, and PSM rate. High-grade malignancy (Gleason score >3 + 4=7) was seen in 26% of TZ cancers which compared with 44% of APZ cancers and 56% of PPC cancers. The rate of EPE was significantly higher in APZ when compared with TZ cancer ( P< 0.0005); however, the biochemical recurrence rate was not significantly different between the groups. The prevalence of APC in radical prostatectomy specimens has increased in recent times, in association with earlier detection at a stage amenable to curative surgical treatment. APC, when compared with PPC, is less commonly high grade with less frequent EPE, despite the APC group having larger tumors and a higher PSM rate at presentation. However, not all anterior cancers are indolent. Anterior cancers are more commonly seen in the APZ than the TZ and APZ cancers appear more locally aggressive than TZ cancers.

Development and External Validation of a Novel Nomogram to Predict the Probability of Pelvic Lymph-node Metastases in Prostate Cancer Patients Using Magnetic Resonance Imaging and Molecular Imaging with Prostate-specific Membrane Antigen Positron Emission Tomography.

BACKGROUND: Preoperative assessment of the probability of pelvic lymph-node metastatic disease (pN1) is required to identify patients with prostate cancer (PCa) who are candidates for extended pelvic lymph-node dissection (ePLND). OBJECTIVE: To develop a novel intuitive prognostic nomogram for predicting pathological lymph-node (pN) status in contemporary patients with primary diagnosed localized PCa, using preoperative clinical and histopathological parameters, magnetic resonance imaging (MRI), and prostate-specific membrane antigen (PSMA) positron emission tomography (PET). DESIGN, SETTING, AND PARTICIPANTS: In total, 700 eligible patients who underwent robot-assisted radical prostatectomy and ePLND were included in the model-building cohort. The external validation cohort consisted of 305 surgically treated patients. Logistic regression with backward elimination was used to select variables for the Amsterdam-Brisbane-Sydney nomogram. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance of the final model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analyses. Models were subsequently validated in an external population. RESULTS AND LIMITATIONS: The Amsterdam-Brisbane-Sydney nomogram included initial prostate-specific antigen value, MRI T stage, highest biopsy grade group (GG), biopsy technique, percentage of systematic cores with clinically significant PCa (GG ≥2), and lymph-node status on PSMA-PET. The AUC for predicting pN status was 0.81 (95% confidence interval [CI] 0.78-0.85) for the final model. On external validation, the Amsterdam-Brisbane-Sydney nomogram showed superior discriminative ability to the Briganti-2017 and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms (AUC 0.75 [95% CI 0.69-0.81] vs 0.67 [95% CI 0.61-0.74] and 0.65 [95% CI 0.58-0.72], respectively; p < 0.05), and similar discriminative ability to the Briganti-2019 nomogram (AUC 0.78 [95% CI 0.71-0.86] vs 0.80 [95% CI 0.73-0.86]; p = 0.76). The Amsterdam-Brisbane-Sydney nomogram showed excellent calibration on external validation, with an increased net benefit at a threshold probability of ≥4%. CONCLUSIONS: The validated Amsterdam-Brisbane-Sydney nomogram performs superior to the Briganti-2017 and MSKCC nomograms, and similar to the Briganti-2019 nomogram. Furthermore, it is applicable in all patients with newly diagnosed unfavorable intermediate- and high-risk PCa. PATIENT SUMMARY: We developed and validated the Amsterdam-Brisbane-Sydney nomogram for the prediction of prostate cancer spread to lymph nodes before surgery. This nomogram performs similar or superior to all presently available nomograms.