68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery). RESULTS: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%. CONCLUSIONS: SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

Detection and localisation of primary prostate cancer using 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology.

OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.

Combined Utility of 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Predicting Prostate Biopsy Pathology.

BACKGROUND: 68Gallium-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions. OBJECTIVE: To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 200 men who underwent 68Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary outcomes were detection of grade group (GG) 3-5 and GG 2-5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via 68Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy. RESULTS AND LIMITATIONS: The median SUVmax was greater for GG 3-5 tumours (6.40, interquartile range [IQR] 4.47-11.0) than for benign and GG 1-2 tumours (3.14, IQR 2.55-3.91; p < 0.001). The median SUVmax was greater for GG 3 (5.70, IQR 3.68-8.67) than for GG 2 (3.47, IQR 2.70-4.74; p < 0.001). For GG 3-5 disease, sensitivity was 86.5%, 95.9%, and 98.6%, and the negative predictive value (NPV) was 88.4%, 88.5%, and 93.3% using SUVmax ≥4, a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3-5, and both, respectively. This combined model detected more GG 3-5 disease than mpMRI alone (98.6% vs 95.9%; p = 0.04). SUVmax was an independent predictor of csPCa for GG 3-5 disease only (odds ratio 1.27 per unit, 95% confidence interval 1.13-1.45). Our results are limited by the retrospective study design. CONCLUSIONS: Greater SUVmax on 68Ga-PSMA-11 PET/CT is associated with detection of GG 3-5 cancer on biopsy. The combination of PI-RADS score and SUVmax provides higher sensitivity and NPV than either alone. 68Ga-PSMA-11 PET/CT may be useful alongside mpMRI in improving risk stratification for localised disease. PATIENT SUMMARY: The amount of a radioactive tracer taken up in the prostate during a type of scan called PET (positron emission tomography) can predict whether aggressive prostate cancer is likely to be found on biopsy. This may complement the more usual type of scan, MRI (magnetic resonance imaging), used to detect prostate cancer.

The role of open radical nephrectomy in contemporary management of renal cell carcinoma.

Radical nephrectomy (RN) remains a cornerstone of the management of localised renal cell carcinoma (RCC). RN involves the en bloc removal of the kidney along with perinephric fat enclosed within Gerota's fascia. Key principles of open RN include appropriate incision for adequate exposure, dissection and visualisation of the renal hilum, and early ligation of the renal artery and subsequently renal vein. Regional lymph node dissection (LND) facilitates local staging but its therapeutic role remains controversial. LND is recommended in patients with high risk clinically localised disease, but its benefit in low risk node-negative and clinically node-positive patients is unclear. Concomitant adrenalectomy should be reserved for patients with large tumours with radiographic evidence of adrenal involvement. Despite a recent downtrend in utilisation of open RN due to nephron-sparing and minimally invasive alternatives, there remains a vital role for open RN in the management of RCC in three domains. Firstly, open RN is important to the management of large, complex tumours which would be at high risk of complications if treated with partial nephrectomy (PN). Secondly, open RN plays a crucial role in cytoreductive nephrectomy (CN) for metastatic RCC, in which the laparoscopic approach achieves similar results but is associated with a high reoperation rate. Finally, open RN is the current standard of care in the management of inferior vena caval (IVC) tumour thrombus. Management of tumour thrombus requires a multidisciplinary approach and varies with cranial extent of thrombus. Higher level thrombus may require hepatic mobilisation and circulatory support, whilst the presence of bland thrombus may warrant post-operative filter insertion or ligation of the IVC.

Adherence to Active Surveillance Protocols for Low-risk Prostate Cancer: Results of the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance Initiative.

BACKGROUND: Active surveillance (AS) enrolment criteria and follow-up schedules for low-risk prostate cancer vary between institutions. However, uncertainty remains about adherence to these protocols. OBJECTIVE: To determine adherence to institution-specific AS inclusion criteria and follow-up schedules within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively assessed the data of 15 101 patients from 25 established AS cohorts worldwide between 2014 and 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adherence to individual AS inclusion criteria was rated on a five-point Likert scale ranging from poor to excellent. Nonadherence to follow-up schedules was defined as absence of repeat biopsy 1 yr after the scheduled date. Cohorts were pooled into annual and Prostate Cancer Research International: Active Surveillance (PRIAS)-based biopsy schedules, and a generalised linear mixed model was constructed to test for nonadherence. RESULTS AND LIMITATIONS: Serum prostate-specific antigen (PSA) inclusion criteria were followed in 92%, Gleason score (GS) criteria were followed in 97%, and the number of positive biopsy cores was followed in 94% of men. Both age and tumour stage (T stage) criteria had 99% adherence overall. Pooled nonadherence rates increased over time-8%, 16%, and 34% for annual schedules and 11%, 30%, and 29% for PRIAS-based schedules at 1, 4, and 7 yr, respectively-and did not differ between biopsy schedules. A limitation is that our results do not consider the use of multiparametric magnetic resonance imaging. CONCLUSIONS: In on-going development of evidence-based AS protocols, variable adherence to PSA and GS inclusion criteria should be considered. Repeat biopsy adherence reduces with increased duration of surveillance, independent of biopsy frequency. This emphasises the importance of risk stratification at the commencement of AS. PATIENT SUMMARY: We studied adherence to active surveillance protocols for prostate cancer worldwide. We found that inclusion criteria were generally followed well, but adherence to repeat biopsy reduced with time. This should be considered when optimising future active surveillance protocols.