Prediction of biochemical recurrence after radical prostatectomy from primary tumour characteristics.

OBJECTIVES: To construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour. PATIENTS AND METHODS: Patients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence-free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre- and post-surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA-PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria. RESULTS: Data from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3-year BRFS for both pre- and post-surgical models. SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 66% to 42% for a patient aged 65 years with typical pre-surgical parameters (PSA level 8 ng/mL, Prostate Imaging-Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post-surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed. CONCLUSION: Tumour SUVmax on diagnostic PSMA-PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

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.

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.

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.

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.

UrethroNAV: the aetiology and extent of idiopathic urethral stricture in an Australian population.

Background: Lichen sclerosus (LS) is considered a causative factor in 10% of cases of idiopathic urethral stricture disease (IUSD), which is important for determining management strategies due to the underlying pathophysiology. Traditional excision urethroplasty may not be effective as inflammation often extends beyond the macroscopic stricture. This pilot study aims to answer two research questions: is LS an underlying cause of some idiopathic cause of strictures, and, if there is histological evidence suggesting predisposition of the surrounding tissue to strictures. Methods: Biopsies were taken from the stricture site as well as 1 and 2 cm proximal and distal in patients with IUSD. Histological features, including macroscopic and microscopic findings, were reported, including the presence of LS, hyperkeratosis, epidermal changes, lichenoid infiltrates, ulceration, scarring, and inflammation. Methylene blue was used to aid in locating damaged urothelium. Patients were prospectively followed up after urethroplasty. Results: From 109 urethroplasties performed between 2019 to 2022, 15 male patients were enrolled after meeting specific inclusion criteria. These criteria included a diagnosis of IUSD and the absence of any evidence of trauma, macroscopic inflammatory disease, or previous endoscopic instrumentation of the urethra. Patients had to be at least 16 years old and medically suitable for undergoing urethroplasty. The study was approved by the hospitals ethics committees. None had macroscopic evidence of LS. One patient had microscopic evidence of LS at the 2 cm proximal biopsy only. A total of 93% of patients had scarring proximal and distal to the stricture, while 20-40% had inflammatory change. The patient with microscopic LS and two inflammatory change patients had stricture recurrence after urethroplasty. Additionally, one patient with inflammatory changes was diagnosed with penile intraepithelial neoplasia (PeIN) and underwent partial penectomy. Conclusions: Findings suggest that an underlying cause of IUSD could be LS. Additionally, the pathophysiology may involve scarring and inflammation beyond the limits of the stricture with extension distal from the stricture site. Careful evaluation for concomitant urethral pathology should be considered in cases of inflammatory changes. These findings should be considered in the surgical management of IUSD and warrant further research into the role of routine biopsy and drug targets in USD.

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.

Paediatric xanthogranulomatous pyelonephritis with reno-psoas fistula, psoas abscess and migration of renal calculi.

Xanthogranulomatous pyelonephritis (XGP) is a rare form of chronic pyelonephritis characterized by granulomatous tissue replacing renal parenchyma, primarily in adults. It's often linked to chronic obstruction, urolithiasis, and pyelonephritis, with rare associations with psoas abscess or fistula. A 15-year-old girl, initially treated conservatively for suspected pyelonephritis, underwent CT imaging due to non-response. This revealed XGP with a sizable psoas abscess caused by a kidney-psoas muscle fistula and renal calculus migration. Treatment involved percutaneous abscess drainage, open right nephrectomy, and a prolonged antibiotic regimen.

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

INTRODUCTION: Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning. METHODS: Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality. RESULTS: Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement. CONCLUSIONS: PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.

The role of dual tracer PSMA and FDG PET/CT in renal cell carcinoma (RCC) compared to conventional imaging: A multi-institutional case series with intra-individual comparison.

PURPOSE: The objective of this study was to perform an intra-individual dual tracer comparison of Fluorodeoxyglucose (FDG) and Prostate Specific Membrane Antigen (PSMA) computed tomography (CT)/Positron Emission Tomography (PET) against standard of care (SOC) imaging for the characterisation, staging and restaging of renal cell carcinoma (RCC). METHODS: A multicentre retrospective cohort study was performed at 3 major tertiary referral institutions in Brisbane, Australia between 2015 and 2020. All patients who underwent both PSMA and FDG PET/CT following SOC imaging for investigation of RCC were identified. Clinical details, imaging characteristics and histopathology were collected prior to univariate statistical analysis. RESULTS: Eleven patients who underwent dual tracer PET/CT were included. Mean age was 65.5 years (SD 8.8). Most patients were male (64%) with clear cell morphology (91%). The indication for dual tracer PET was staging (36%) and restaging after radical/partial nephrectomy (64%). Primary tumour assessment showed mixed avidity patterns (concordant 40%, discordant favouring PSMA 20%, and FDG 40%). Metastatic disease assessment showed concordant avidity in 6 patients (55%), concordant negative in 3 (27%), and discordant uptake favouring PSMA. PET outperformed SOC imaging for assessment of metastatic disease in 5 patients (45%) and equivalent for the remainder. A change in management was noted in three cases (27%). CONCLUSION: Dual tracer FDG and PSMA PET/CT for assessment of primary and metastatic RCC were mostly concordant. PET imaging outperformed conventional imaging and led to a change in management for 1 in 4 patients. Further studies with larger samples sizes are required to validate these findings and identify characteristics to guide patient selection for selective or dual tracer use.

Lichen sclerosus presenting as an isolated bulbar urethral stricture.

Lichen sclerosus (LS) is a chronic inflammatory condition of the anogenital skin that can cause significant urinary and sexual dysfunction in men, particularly by means of destructive urethral disease. LS is traditionally thought to progress from the meatus with migration along the urethra proximally, however we present a case describing an isolated bulbar urethral stricture secondary to LS. To our knowledge, this has only been reported in the literature in one previous study. Clinician recognition of LS as a potential cause of isolated bulbar urethral stricture disease is important as this has ramifications on follow up and successful management.

Redo pelvic fracture urethral injury repair: The case for tadalafil.

OBJECTIVE: To define the role of tadalafil in improving outcomes of redo urethroplasty for pelvic fracture urethral injury (PFUI). PFUI is common in developing countries, invariably as a result of road traffic trauma. Repair is complex, and redo cases are even more challenging. MATERIAL AND METHODS: This was a longitudinal prospective nonrandomized study between 2017 and 2019. Men undergoing redo-urethroplasty were nonrandomized into two groups. Group 1 received tadalafil 5 mg the next day after surgery and continued for 3 months, and group 2 did not receive tadalafil. Inclusion criteria were patients undergoing redo-urethroplasty willing to trial low-dose tadalafil post-operatively. Exclusion criteria were <18 years, females, primary cases, and complex cases such as recto-urethral fistula. Average follow-up was 19.5 months. RESULTS: Sixty patients were enrolled (29 in group 1 and 31 in group 2). Mean age was 31 years. These patients had 1-3 prior failed urethroplasties. Most required step 3 anastomotic urethroplasty (68.3%). Success was defined as absence of symptoms and no need for surgical intervention. Failure was defined as redo urethroplasty or >1 endoscopic intervention. Primary success was 83.3%. Success with tadalafil was 96.6%, compared to 71.0% in the non-Tadalafil group (P » .0008). Only one patient on tadalafil failed, compared with nine in the non-tadalafil group. Secondary success rate was defined as the need for a single subsequent endoscopic intervention and was 93.3%. CONCLUSION: In our series, there was improved outcome with using tadalafil in patients having redo urethroplasty for PFUI. Further trials should be done to evaluate the use in all PFUI cases.

Histological findings of totally embedded robot assisted laparoscopic radical prostatectomy (RALP) specimens in 1197 men with a negative (low risk) preoperative multiparametric magnetic resonance imaging (mpMRI) prostate lobe and clinical implications.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) has become a popular initial investigation of an elevated PSA and is being incorporated into active surveillance protocols. Decisions on prostate cancer investigation and management based solely on a normal mpMRI remains controversial. Histopathological findings of a totally embedded normal mpMRI lobe are rarely described. METHODS: A retrospective review of the histological findings of negative preoperative mpMRI lobes in men treated by robot assisted laparoscopic radical prostatectomy (RALP). Inclusion criteria included a preoperative low risk mpMRI for both lobes (Prostate Imaging-Reporting and Data System (PIRADS) ≤ 2) or one negative lobe (with a PIRADS 3-5 in the opposite lobe). RESULTS: A single normal mpMRI lobe was identified in 1018 men (PIRADS 3-5 group). Both lobes were normal in 179 men (PIRADS ≤ 2 group). Prostate cancer was identified in 47.6% (485/1018) of the normal mpMRI lobe opposite a PIRADS 3-5 lesion, including 13.2% (134/1018) with >0.5 cc of International Society of Urologic Pathologists (ISUP) grade 2, or a higher grade cancer. ISUP grade 4-5 was only identified in 2% (20/1018). Compared to RALP histology of the PIRADS 3-5 mpMRI tumour, a pathological ISUP upgrade in the normal mpMRI lobe was identified in 58/1018 men (5.7%). In the PIRADS ≤ 2 group extraprostatic extension occurred in 19% (34/179) and seminal vesicle invasion (pT3b) in 3.9% (7/179). There was no difference in margin status between the PIRADS 3-5 and ≤2 groups (p = 0.247). CONCLUSIONS: mpMRI underestimates tumour grade and volume compared to totally embedded histopathological analysis of RALP specimens, although ISUP grade 4-5 cancer is uncommon. Our analysis provides useful insight into the multifocality of prostate cancers, and highlights the utility of systematic biopsy, in addition to targeted biopsies. These results have ramifications for clinical decisions on prostate cancer management based solely on the mpMRI appearance, including active surveillance.

The use of 68Ga-PET/CT PSMA to determine patterns of disease for biochemically recurrent prostate cancer following primary radiotherapy.

BACKGROUND: 68Ga-PET/CT PSMA scan is being increasingly used for the staging of biochemically recurrent disease. Early identification of recurrent disease after radiotherapy is important in considering suitability for early salvage therapy to improve prognosis. The aim is to identify patterns of suspected prostate cancer recurrence in relation to post-radiotherapy PSA levels, especially below the accepted Phoenix definition of PSA failure (PSA nadir + 2). METHODS: This was a retrospective single tertiary institution cohort study of consecutive men between July 2014 and June 2018 who received a 68Ga-PSMA PET/CT for elevated PSA levels following radiotherapy as primary treatment of prostate cancer. The primary outcome measure was to determine the relationship between pre-scan PSA and the probability of identifying PSMA-avid disease suggestive of recurrent prostate cancer. RESULTS: Two hundred and seventy-six patients met criteria for inclusion. The median PSA was 3.60 ng/mL. The overall detection rate for suspected recurrent prostate cancer was 86.3%. Local recurrence was the most common site, occurring in 56.9% (157/276) of men, with isolated local recurrence in 32.6% (90/276). A total of 75.3% (55/73) of men below Phoenix criteria had scans suggestive of recurrent disease, with 52.1% of men having salvageable disease. The regions surrounding the iliac arteries were the most common areas of nodal metastatic disease, with 55.6% of recurrence occurring in the iliac regions. CONCLUSIONS: 68Ga-PSMA PET/CT frequently identifies suspected recurrent disease prior to the accepted Phoenix definition of PSA nadir +2. Prospective outcome studies are required to determine if early identification of local recurrence improves outcomes by increasing the use of salvage local treatments and whether earlier identification of metastatic disease may improve outcomes with prompt initiation of multimodality therapies.