Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Near-infrared spectroscopy as a novel method of ex vivo bladder cancer tissue characterisation.

OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.

Do alpha blockers reduce the risk of urinary retention post-transperineal prostate biopsy? A systematic narrative review.

BACKGROUND: Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSB). TPB is associated with an infective complication rate of near zero, however, acute urinary retention (AUR) remains the leading complication causing morbidity. Previously in TRUSB, there was weak evidence that alpha-blockers reduce AUR rates, and their usage has been extrapolated to clinical practice with TPB. This review aims to explore if there is an evidence base for using alpha-blockers to prevent AUR following TPB. METHODS: A systematic approach was used to search Ovid Medline and Embase using keywords related to "Transperineal" and "Retention". Articles were then screened by applying inclusion and exclusion criteria to find studies that compared alpha-blocker recipients to no alpha-blocker use in the perioperative period and the subsequent effect on AUR in TPB. RESULTS: 361 records were identified in the initial search to produce 5 studies included in the final review. No randomised controlled trials (RCTs) were identified. One observational study showed a reduction in AUR rate from 12.5% to 5.3% with a single dose of tamsulosin. A previous systematic review of complications associated with prostate biopsy concluded there may be a potential benefit to alpha-blockers given in the TPB perioperative period. Three observational studies demonstrated a harmful effect related to alpha-blocker use; however, this was well explained by their clear limitations. CONCLUSION: Based on this review and the extrapolation from TRUSB data, perioperative alpha-blockers may offer some weak benefits in preventing AUR following TPB. However, there is significant scope and need for an RCT to further develop the evidence base further given the significant gap in the literature and lack of a standard alpha blocker protocol in TPB.

Re-defining 18 F-DCFPyl prostate-specific membrane antigen positron emission tomography detected local recurrence from radical prostatectomy histopathology.

OBJECTIVE: To assess topographic concordance between the histopathological features of patients' radical prostatectomy (RP) specimens and the location of the prostate-specific membrane antigen positron emission tomography (PSMA PET) local recurrences, qualitatively and quantitatively. PATIENTS AND METHODS: Our cohort was selected from the 100 men who received a 18 F-DCFPyL PET scan in the IMPPORT trial (Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213), a prospective non-randomised study completed by GenesisCare Victoria. Eligibility included patients with a rising prostate-specific antigen (PSA) level (>0.2 ng/mL) after RP and PSMA PET detected local recurrence. Histopathological parameters collated included the location of tumour, extraprostatic extension (EPE), and positive margins. Criteria for the location and 'concordance' between histopathological features and local recurrences were pre-defined. RESULTS: A total of 24 patients were eligible; the median age was 71 years, the median PSA level was 0.37 ng/mL, and the time between RP and PSMA PET was 2.6 years. In all, 15 patients had recurrences within the vesicourethral anastomotic region and nine within the lateral surgical margins. There was 100% concordance in the left-right plane between tumour location and local recurrence, with 79% of these lesions concordant three-dimensionally; across craniocaudal, left-right, and anterior-posterior planes. In all, 10 of the 16 (63%) patients with EPE and five of the nine patients with positive margins had three-dimensional concordance between their pathology and their local recurrence. In quantitative assessment, 17 of the 24 patients, had local recurrences that correlated with the location of their original tumour in the craniocaudal plane. CONCLUSION: Local recurrence is highly concordant with the position of the tumour within the prostate. Predicting the location of local recurrence using the location of the EPE and positive margins is less helpful. Further investigation into this field, could impact surgical technique and salvage radiotherapy clinical target volume.

Xanthogranulomatous pyelonephritis: a systematic review of treatment and mortality in more than 1000 cases.

OBJECTIVES: To systematically review the current demographics, treatment and mortality rate associated with xanthogranulomatous pyelonephritis (XGP) and to test the hypothesis that the weighted pooled peri-operative mortality rate will be <10%. METHODS: Searches were performed of the Cochrane, Embase and Medline databases and the grey literature for studies published during the period 1 January 2000 to 30 August 2021. Eligible studies reported cohorts of ≥10 predominantly adult patients with XGP and described either average patient age or mortality rate. RESULTS: In total, 40 eligible studies were identified, representing 1139 patients with XGP. There were 18 deaths, with a weighted pooled peri-operative mortality rate of 1436 per 100 000 patients. The mean age was 49 years, 70% of patients were female and 28% had diabetes mellitus. The left kidney was more commonly affected (60%). Four patients had bilateral XGP, and all of whom survived. Renal or ureteric stones were present in 69% of patients, including 48% with staghorn calculi. Urine culture was positive in 59% of cases. Fistulae were present in 8%. Correct preoperative diagnosis occurred in only 45% of patients. Standard treatment continues to comprise a short cause of antibiotics and open radical (total) nephrectomy. Preoperative decompression occurred in 56% of patients. When considered at all, laparoscopic nephrectomy was performed in 34% of patients. Partial nephrectomy was conducted in 2% of patients. CONCLUSIONS: Xanthogranulomatous pyelonephritis has a lower mortality rate than historically reported. A typical patient is a woman in her fifth or sixth decade of life with urolithiasis. While open radical nephrectomy remains the most common treatment method, laparoscopic, and to a lesser degree partial nephrectomy, are feasible in well selected patients.

Investigating PSMA-PET/CT to resolve prostate MRI PIRADS4-5 and negative biopsy discordance.

BACKGROUND: To determine the utility of diagnostic 18F-DCPyL PSMA-PET/CT to aid management of men with highly suspicious multiparametric MRI prostate (PIRAD 4-5 lesions) and discrepant negative prostate biopsy. METHODS: A multicentre prospective consecutive case series was conducted (2018-2021), recruiting men with prior mpMRI prostate PIRADS 4-5 lesions and negative prostate biopsy. All men had 18F-DCPyL PSMA-PET/CT with subsequent management based on the concordance between MRI and PET: (1) Concordant lesions were biopsied using in-bore MRI targeting; (2) PSMA-PET/CT avidity without MRI correlate were biopsied using cognitive/software targeting with ultrasound guidance and (3) Patients with negative PET/CT were returned to standard of care follow-up. RESULTS: 29 patients were recruited with 48% (n = 14) having concordant MRI/PET abnormalities. MRI targeted biopsy found prostate cancer in six patients, with grade groups GG3 (n = 1), GG2 (n = 1), GG1 (n = 4) found. Of the 20 men who PSMA-PET/CT avidity and biopsy, analysis showed higher SUVmax (20.1 vs 6.8, p = 0.036) predicted prostate cancer. Of patients who had PSMA-PET avidity without MRI correlate, and those with no PSMA-PET avidity, only one patient was subsequently found to have prostate cancer (GG1). The study is limited by small size and short follow-up of 17 months (IQR 12.5-29.9). CONCLUSIONS: PSMA-PET/CT is useful in this group of men but requires further investigation. Avidity (higher SUVmax) that correlates to the mpMRI prostate lesion should be considered for targeted biopsy.

Non-prostate cancer tumours: incidence on 18F-DCFPyL PSMA PET/CT and uptake characteristics in 1445 patients.

PURPOSE: With increasing use of PSMA PET/CT in the staging and restaging of prostate cancer (PCa), the identification of non-prostate cancer tumours (NPCaT) has become an increasing clinical dilemma. Atypical presentations of PSMA expression in prostate cancer and expression in NPCaT are not well established. Understanding the normal and abnormal distribution of PSMA expression is essential in preparing clinically relevant reports and in guiding multidisciplinary discussion and decisions. METHODS: Retrospective review of 1445 consecutive 18F-DCFPyL PSMA PET/CT studies by experienced radiologists and nuclear medicine physicians. Lesions indeterminate for PCa were identified. Correlation was made with patient records, biopsy results, and dedicated imaging. Lesions were then categorized into four groups: 1. Confirmed prostate cancer, metastases, 2. NPCaT 3. Benign, and 4. Indeterminate lesions. RESULTS: 68/1445 patients had lesions atypical for prostate cancer metastases. These comprised 8/68 (11.8%) atypical prostate cancer metastases, 17/68 (25.0%) NPCaT, 29/68 (42.6%) indeterminate, and 14/68 (20.6%) benign. In the context of the entire cohort, these are adjusted to 8/1445 (0.6%), 17/1445 (1.2%), 29/1445 (2.0%), and 14/1445 (1.0%) respectively. With the exception of Renal Cell Carcinoma (RCC), NPCaT demonstrated no or low PSMA expression. A similar trend was also observed for indeterminate and benign lesions. Conversely, most atypical PCa metastases demonstrated intermediate or high PSMA expression. CONCLUSION: 18F-DCFPyL PSMA PET/CT detection of NPCaT is low. Lesions demonstrating intermediate to high PSMA expression were exclusively prostate cancer metastases, aside from RCC, and lesions detected in organs with high background expression.

Pathological predictors of 18 F-DCFPyL prostate-specific membrane antigen-positive recurrence after radical prostatectomy.

OBJECTIVES: To assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on subsequent 18 F-DCFPyL positron emission tomography/computed tomography (PET/CT) in patients with biochemical failure (BF). PATIENTS AND METHODS: Retrospective analysis of combined 18 F-DCFPyL PET/CT database of patients from centres in Australia and New Zealand was performed. A total of 205 patients presenting with BF after RP were included in this study. Imaging findings on 18 F-DCFPyL PET/CT were recorded and correlated with the PSA characteristics at BF and pathological features of the original tumour. RESULTS: Of the 205 patients, 120 (58.5%) had evidence of abnormal prostate-specific membrane antigen (PSMA) expression compatible with recurrent prostate cancer. Increasing PSA velocity (P = 0.01), International Society of Urological Pathology (ISUP) Grade Group (P = 0.02), lymphovascular invasion (P = 0.05) and nodal positivity (P = 0.02) at the time of RP were more likely to demonstrate PSMA positivity. Multivariable logistic regression revealed a higher PSA level prior to PSMA PET/CT (P < 0.01), adjuvant radiotherapy (P = 0.09), Gleason score ≥8 (P < 0.01) and nodal positivity (P = 0.05) were all predictive of PSMA positivity. CONCLUSION: 18 F-DCFPyL PET/CT positivity, both generally and site specific, correlates with PSA and RP pathological factors. Our results echo cohorts focussing on post-RP patients, those imaged with 68 Ga-PSMA and those concerning biochemical persistence. Nomograms that include risk factors for 'PSMA-positive recurrence' in the BF population may increase the catchment of patients with disease confined to the prostate bed or pelvis who have a greater probability of prolonged disease-free survival.

Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

BACKGROUND: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management. METHODS: In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358. FINDINGS: From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0·0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10-22] vs 41 [28%] men [21-36]; p=0·008) and had more equivocal findings (23% [17-31] vs 7% [4-13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8-12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT. INTERPRETATION: PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning. FUNDING: Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.

[18F]DCFPyL PET/CT in detection and localization of recurrent prostate cancer following prostatectomy including low PSA < 0.5 ng/mL.

PURPOSE: The primary aim of this retrospective multicenter analysis was to assess the performance of PSMA PET/CT using [18F]DCFPyL in the detection and localization of recurrent prostate cancer post radical prostatectomy (RP). Particular reference is given to low PSA groups < 0.5 ng/mL to aid discussion around the inclusion of this group in PSMA guidelines and funding pathways. METHODS: Retrospective analysis of combined PSMA database patients from centers in Australia and New Zealand. Two hundred twenty-two patients presenting with recurrence post RP were stratified into five PSA groups (ng/mL): 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥ 2. Lesions detected by [18F]DCFPyL PET/CT were recorded as local recurrence, locoregional nodes, and metastases. RESULTS: Of 222 patients, 155 (69.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer. The detection efficacies for [18F]DCFPyL PET/CT were 91.7% (44/48) for PSA levels ≥ 2 ng/mL, 82.1% (23/28) for PSA levels 1-1.99 ng/mL, 62.8% (27/43) for PSA levels 0.5-0.99 ng/mL, 58.7% (54/92) for PSA levels 0.2-0.49 ng/mL, and 63.6% (7/11) for PSA levels ≤ 0.2 ng/mL. In those with PSA < 0.5 ng/mL, 47.6% (49/103) had detectable lesions, 71.4% (35/49) had disease confined to the pelvis, 22.4% (11/49) had prostate bed recurrence, 49.0% (24/49) had pelvic lymph nodes, and 28.6% (14/49) had extra pelvic disease. CONCLUSION: [18F]DCFPyL PET/CT has a high detection rate in recurrence following RP even at low PSA levels with similar detection levels in the PSA subgroups < 0.5 ng/mL. Employing rigid PSA thresholds when constructing guidelines for PSMA PET/CT funding eligibility may result in a significant number of patients below such thresholds having delayed or inappropriate treatment.

Patterns of disease detection using [18F]DCFPyL PET/CT imaging in patients with detectable PSA post prostatectomy being considered for salvage radiotherapy: a prospective trial.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [18F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy. METHODS: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [18F]DCFPyL tracer and a diagnostic CT. The detection rates of [18F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported. RESULTS: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [18F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [18F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [18F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [18F]DCFPyL administration. CONCLUSIONS: [18F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [18F]DCFPyL PET/CT scan. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true ).

Funding of prostate magnetic resonance imaging leads to fewer biopsies and potential savings to health systems in the management of prostate cancer.

OBJECTIVES: To assess the impact of the introduction of multiparametric magnetic resonance imaging of the prostate (mpMRIp) on the number of prostate biopsies performed in Australia. METHODS: Australian Medicare published statistics from 1 July 2007 to 30 June 2019 were obtained from publically available databases for prostate-specific antigen (PSA) testing, prostate biopsy, and mpMRIp. Analysis was divided into three time periods broadly based on availability of mpMRI to the Australian public: 2007-2012 (no mpMRIp), 2012-2018 (mpMRIp available, privately funded), and 2018-2019 (mpMRIp available with Medicare funding). Introduction of mpMRIp was hypothesised to reduce the number of prostate biopsies performed. PSA testing numbers were used as a control. The economics model, proposed by the Medical Services Advisory Committee (MSAC), was analysed for cost savings. RESULTS: Accounting for variations in PSA testing, the introduction of mpMRIp from 2012 coincided with a reduction in the number of prostate biopsies by an average of 354.7/month (95% CI 175, 534.4; P < 0.001). Whilst the number of mpMRIp performed for the initial 12 months was underestimated by the MSAC at 38 470 vs 20 149 (+$8.3 million Australian dollars), we estimate the annual savings from reduced number biopsies and biopsy-associated complications to be $13.2 ± 9.6 million. CONCLUSION: Availability of mpMRIp in Australia has correlated with a significant reduction in prostate biopsy rates, with an estimated annual saving of $13.2 ± 9.6 million. Government funding of this diagnostic service has the potential to improve health equity and save on health expenditure.

Long-term oncological outcomes of patients with paratesticular sarcoma.

OBJECTIVES: To present long-term oncological outcomes of patients with paratesticular sarcoma treated by a multidisciplinary team. PATIENTS AND METHODS: Patients managed at the Princess Margaret Cancer Centre, between 1990 and 2012, were analysed. A sarcoma expert performed central pathology review. Kaplan-Meier graphs compared local recurrence (LR), metastasis, and overall survival (OS) of patients treated with hemiscrotectomy vs those who did not. Univariable Cox proportional hazards analysis was performed to delineate predictors of LR, metastasis, and OS. RESULTS: Overall, 51 patients with a median (interquartile range) follow-up of 132 (51.6-226.8) months were analysed. At presentation, 92.2% (47 patients) had localised disease. Only five patients (9.8%) had undergone initially planned hemiscrotectomy. Completion and salvage hemiscrotectomy was performed in 25 (54.3%) and seven (15.2%) patients, respectively. Recurrence and metastasis occurred in 12 (25.5%) and 10 patients (19.6%), respectively. At the last follow-up, 21.6% (11 patients) had died, with eight dying from their disease. Kaplan-Meyer graphs demonstrated that hemiscrotectomy improved LR (median not reached vs 62.4 months, log-rank P = 0.008) and OS (median not reached vs 168 months, log-rank P = 0.081). Univariable analysis found hemiscrotectomy to be associated with a lower LR rate (hazard ratio [HR] 0.21, P = 0.02), whilst positive margins at initial surgery were associated with increased LR (HR 4.81, P = 0.047). No metastasis predictors were found, but age (HR 1.04, 95% confidence interval [CI] 1.0-1.08; P = 0.02) and non-localised disease at presentation (HR5.17, 95% CI 1.33-20.06; P = 0.017) were associated with worse OS. CONCLUSION: Paratesticular sarcoma is a rare tumour, predominantly manifesting as localised disease. Most patients receive an initial suboptimal oncological surgery. Improved long-term outcomes are demonstrated following early hemiscrotectomy.

Evaluation of the accuracy of multiparametric MRI for predicting prostate cancer pathology and tumour staging in the real world: an multicentre study.

OBJECTIVES: To assess the accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of significant prostate cancer in men undergoing radical prostatectomy (RP) in an Australian multicentre setting, and to assess concordance between mpMRI and RP for local tumour staging and index lesion locations. PATIENTS AND METHODS: Men who underwent mpMRI within 12 months of RP between January 2013 and August 2016 at three Australian sites were included (Central Coast, NSW, St Vincents Hospital, Melbourne, Vic., and Bendigo Hospital, Vic.). The results of mpMRI were compared with the final RP specimen to analyse the performance of mpMRI for significant prostate cancer detection, index lesion localization, prediction of T3 disease and lymph node metastasis. A comparison between mpMRI cases performed using the technical and reporting specifications of Prostate Imaging Reporting and Data System (PI-RADS) version 1 and version 2 was also performed. Data analysis was performed using spss 24.0. RESULTS: A total of 235 cases were included for analysis. mpMRI PI-RADS score ≥3 had a 91% sensitivity and 95% positive predictive value (PPV) for significant prostate cancer at RP. The overall concordance between index lesion location on mpMRI and RP specimen was 75%. The sensitivity for predication of significant prostate cancer was higher in the PI-RADS version 2 cases compared with PI-RADS version 1 (87-99%; P = 0.005). Index lesion concordance was higher in the PI-RADS version 2 group (68% vs 91%; P = 0.002). mpMRI had a 38% sensitivity, 95% specificity, 90% PPV and 57% negative predictive value for extraprostatic disease. Sensitivity for prediction of T3 disease improved from 30% to 62% (P = 0.008) with PI-RADS version 2. CONCLUSIONS: In patients undergoing RP, an abnormal mpMRI is highly predictive (95% PPV) of significant prostate cancer, with an index lesion concordance of 75%. There has been a significant improvement in accuracy after the adoption of PI-RADS version 2 technical specifications and reporting criteria; however; further study is required to determine if this is attributable to improved experience with mpMRI or changes in the PI-RADS system.

The role of prostate-specific membrane antigen PET/computed tomography in primary staging of prostate cancer.

PURPOSE OF REVIEW: Functional imaging with PET combined with computed tomography (CT) is of emerging interest in prostate cancer (PCa). Development of prostate-specific membrane antigen (PSMA) radiolabelled ligands has thrust PET/CT into the limelight as an alternative to conventional imaging techniques, and the evidence base to support its utility in primary staging of newly diagnosed PCa is rapidly growing. This review focuses on the most recent and important publications evaluating PSMA PET/CT in primary staging of PCa. RECENT FINDINGS: Three recent meta-analyses have reported Ga-PSMA PET/CT to demonstrate superior sensitivity and specificity for pelvic lymph node detection than conventional imaging. A recent systematic review also suggests Ga-PSMA PET/CT to be superior to bone scan for identifying bone metastases. However, the majority of studies are of a retrospective nature, and few provide histopathological correlation of PSMA PET/CT findings. Data from prospective studies are awaited to determine accuracy and management impact of PSMA PET/CT in primary staging. SUMMARY: PSMA PET/CT is rapidly altering the landscape of primary staging in PCa. It appears to be superior to conventional imaging for detecting regional and distant metastasis, though caution should be applied given the lack of prospective studies assessing how significant findings should be integrated into patient management. PSMA PET/CT could potentially become the gold standard for primary staging of high-risk PCa if future prospective data can prove its validity in this space.

Hospital volume and perioperative outcomes for radical cystectomy: a population study.

OBJECTIVES: To evaluate the association between hospital volume and perioperative outcomes of radical cystectomy (RC) using state population data for a contemporary Australian cohort. PATIENTS AND METHODS: Patients undergoing RC for urothelial malignancy in the state of Victoria, Australia between July 2003 and June 2014 were identified using the Victorian Admitted Episodes Dataset (VAED). Hospitals were divided into tertiles according to their caseload per year. Hospitals performing <4 RCs/year were defined as low-volume hospitals (LVH), 4-10 RCs/year as medium-volume hospitals (MVH), and >10 RCs/year as high-volume hospitals (HVH). Perioperative outcomes derived included: in-hospital mortality (IHM), prolonged length of stay (LOS; >14 days), prolonged intensive care unit (ICU) admission (>24 h), and requirement for blood transfusion. The relationship between hospital volume and perioperative outcomes was assessed using logistic regression. RESULTS: During the 11-year study period, 803 patients underwent RC for bladder cancer. The overall IHM rate was 2.2% (LVH 3.7%, MVH 2.5%, HVH 0.9%). Other outcomes observed were prolonged LOS (45%), prolonged ICU admission (31%) and requirement for blood transfusion (56%). On multivariate analysis, LVH was found to be associated with increased IHM (odds ratio [OR] 5.74, P = 0.04) and prolonged ICU admission (OR 11.58, P < 0.001) when compared to HVH. There was a lower rate of prolonged LOS for LVH (OR 0.60, P = 0.01). No significant relationship was identified for LVH and blood transfusion. CONCLUSION: Perioperative outcomes in Victoria are comparable to international standards. Our results add further population study evidence to the volume-outcome relationship in RC. There was a significant association between LVH and both IHM and prolonged ICU admission. This subgroup of patients would appear to benefit from transfer of care to a HVH. The role of centralisation of RC in Australia should be further considered.

An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup.

PURPOSE: We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance. MATERIALS AND METHODS: A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy. RESULTS: A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001). CONCLUSIONS: While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Feasibility for active surveillance in biopsy Gleason 3 + 4 prostate cancer: an Australian radical prostatectomy cohort.

OBJECTIVE: To examine the feasibility of active surveillance for low volume Gleason sum (GS) 3 + 4 disease compared to GS 3 + 3 disease. PATIENTS AND METHODS: Retrospective review of 929 patients, with biopsy proven GS 3 + 3 and 3 + 4 PCa, undergoing upfront radical prostatectomy (RP) was performed. Suitability for AS was adapted from protocols by Royal Marsden Hospital, University of Toronto, and PRIAS by allowing Gleason 3 + 4 disease. The outcomes assessed were adverse pathology at RP (upgrading ≥GS 4 + 3 and/or upstaging ≥pT3) and biochemical recurrence (BCR) after RP. RESULTS: Adverse pathology at RP was compared between GS 3 + 3 vs 3 + 4 groups. When selecting patients using Royal Marsden (n = 714) or University of Toronto (n = 699) protocols, there was statistically significantly more adverse pathology at RP in GS 3 + 4 group (21% vs 31%, P = 0.0028 and 19% vs 33%, P=<0.001 respectively). Using the more stringent PRIAS protocol (n = 198), there was no statistical significant difference in groups. There was no difference in BCR survival between biopsy GS 3 + 3 and 3 + 4 groups, regardless of which AS protocol assessed. Pre-operative PSA and clinical staging were the predictors for BCR. CONCLUSION: Presence of Gleason 3 + 4 at biopsy, when compared to 3 + 3, increases the risk of adverse pathology being present at radical prostatectomy for less stringent selection criteria. When considering AS, a stricter protocol such as PRIAS, limiting PSA density and number of positive cores to ≤2, appears to decrease the risk of adverse pathology. No differences in BCR were seen between biopsy 3 + 3 and 3 + 4 disease, regardless of AS selection criteria.

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

PURPOSE: We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. MATERIALS AND METHODS: Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. RESULTS: A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). CONCLUSIONS: Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk.

Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL).

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy. METHODS: Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. KEY FINDINGS AND LIMITATIONS: Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. PATIENT SUMMARY: In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.