We report the case of an 81-year-old male presenting with lower urinary tract symptoms and a PSA of 39 ng/mL, initially attributed to Escherichia coli prostatitis. Despite PSA normalization with antibiotics, MRI demonstrated a PIRADS 5 lesion in the left transition zone. Histopathological evaluation following transperineal biopsy revealed prostatic malakoplakia. This rare granulomatous condition can mimic prostate cancer both clinically and radiologically. Our case highlights the importance of histological confirmation in atypical presentations to avoid misdiagnosis and overtreatment.

OBJECTIVES:To determine if Australian prostate cancer screening has declined since the Royal Australasian College of General Practitioners (RACGP) recommended against prostate cancer screening in 2009 and correlate screening trends with more advanced disease at radical prostatectomy (RP) in Australia. PATIENTS AND METHODS:Histopathology of patients undergoing RP from 2007 to 2018 in the state of New South Wales (NSW), Australia was accessed from a prospectively maintained pathology database by Douglass Hanly Moir, the largest pathology provider in NSW. Prostate-specific antigen (PSA) testing rates were obtained via the Medicare Statistics database (Australian Government). Population data were obtained from the Australian Institute of Health and Welfare and Bureau of Statistics. RESULTS:Prostate-specific antigen testing decreased significantly in NSW, Australia dropping from 8470 to 4910 tests per 100 000 males from 2009 to 2018, approximately a 5% annual percentage decrease. Histopathology of 17 375 patients who underwent RP during this time showed a 5.4% annual increase in non-organ-confined disease at RP, which was irrespective of Gleason Grade. There was a strong correlation between the decrease in PSA testing with an increase in non-organ-confined disease at RP. CONCLUSIONS:In conclusion, the RACGP guidelines recommending against prostate cancer screening in 2009 correlates strongly with more advanced disease found at RP. This could indicate that patients were presenting later with more advanced disease. However, the increasing use of surveillance of low-grade and favourable intermediate-risk disease and also the potential increasing use of surgery for higher-volume or -grade prostate cancer at diagnosis could impact on the interpretation of our findings. Most international guidelines, as well as the Prostate Cancer Foundation of Australia Guidelines, have now recommended prostate cancer screening in men aged 50-69 years and it is commendable that the latest 2024 RACGP guidelines have been updated to reflect the new evidence supporting prostate cancer screening.

OBJECTIVES:Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC. METHODS:It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists. RESULTS:Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3). Among all 3 groups, group 1 was most likely to diagnose concomitant CIS and PUC in the same specimen but in different tissue fragments (58%). Pagetoid spread was reported to favor CIS predominantly by group 1 (61%). Urologists felt that the term lateral spread/shoulder was unclear (75%) and preferred early PUC (44%) or PUC with early growth (44%). Half (53%) of urologists felt that reporting CIS instead of lateral spread of PUC would change management. CONCLUSIONS:Documentation of flat lesions lacks consensus among pathologists and may benefit from standardized terminology. Moreover, the distinction between CIS and early or lateral spread of PUC is not always clear to urologists and can influence disease management.

Microcystic adenocarcinoma is an uncommon histologic variant of prostate carcinoma. Despite its rarity, it has gained increasing recognition over the past decade for its diagnostic challenges and unclear prognostic significance.Herein, we describe a rare case of metastatic microcystic prostate adenocarcinoma, presenting with discordance between imaging and histologic findings. This report highlights the diagnostic and therapeutic challenges of this pathological entity and the importance of multidisciplinary collaboration in the management of intermediate-risk prostate cancer.

The pathological grade of prostate cancer is the strongest predictor of recurrence. It is unclear whether the better predictor is the composite of all carcinomas within the prostate, or the highest grade lesion (index). The purpose of this study was to determine whether composite or index grade group better predicts biochemical recurrence (BCR). We undertook a retrospective analysis from a prospective institutional cohort study of men who underwent radical prostatectomy for localised prostate cancer between 2009 and 2020, in which an index and composite grade group was reported. The index grade in this study was defined as the highest grade of any tumour, usually with the highest stage, regardless of volume. Multivariate analysis and Kaplan-Meier plots were utilised. A total of 2024 men underwent radical prostatectomy during the study period; we analysed 1605 with composite grade group 2 or 3 prostate cancer. Median preoperative prostate specific antigen (PSA) was 5.9 ng/L, mean follow up was 56.8 months, 54% were pT2, 76% had multifocal disease and 16% had discordant index and composite grades. Patients with discordant index grade group had a higher risk of BCR [hazard ratio (HR) 2.22, p<0.0001]. The prevalence of BCR in the discordant group was higher at 1, 3, 5 and 7 years (4.7% vs 8.9%, 8.3% vs 18.1%, 14.5% vs 28.8% and 22.5% vs 49.5%, respectively). In cases of discordance, a higher index grade group is associated with increased rates of BCR after radical prostatectomy. Index rather than composite grade group should be used to counsel men post-operatively regarding prognosis and follow-up.

To prospectively assess the safety, functional- and oncological-outcomes of irreversible electroporation (IRE) as salvage therapy for radio-recurrent focal prostate cancer in a multicenter setting. Men with focal recurrent PCa after external beam radiation or brachytherapy without metastatic disease on staging imaging and co-registration between mpMRI and biopsies were prospectively included in this multicenter trial. Adverse events were reported following the Clavien-Dindo classification. Validated questionnaires were used for patient-reported functional outcomes. Follow-up consisted of 3 monthly prostate specific antigen (PSA) levels, a 6-month mpMRI and standardised transperineal template mapping biopsies at 12-months. Thereafter follow-up was guided by MRI and/or PSMA-PET/CT and PSA. Local recurrence was defined as any ISUP score ≥2 on biopsies. 37 patients were analysed with a median (interquartile range (IQR)) follow up of 29 (22–43) months. Median age was 71 (53–83), median PSA was 3.5 ng/mL (2.7–6.1). 28 (75.5%) patients harboured intermediate risk and 9 patients (24.5%) high risk PCa. Seven patients (19%) reported self-limiting urgency, frequency, or hematuria (grade 1–2). Seven patients (19%) developed a grade 3 AE; urethral sludge requiring transurethral resection. At 12 months post treatment 93% of patients remained continent and erectile function sufficient for intercourse deteriorated from 35% to 15% (4/27). Local control was achieved in 29 patients (78%) and 27 patients (73%) were clear of local and systemic disease. Four (11%) patients had local recurrence only. Six (16%) patients developed metastatic disease with a median time to metastasis of 8 months. The FIRE trial shows that salvage IRE after failed radiation therapy for localised PCa is safe with minimal toxicity, and promising functional and oncological outcomes. Salvage IRE can offer a possible solution for notoriously difficult to manage radio recurrent prostate tumours.

To assess whether completeness of pelvic lymph node dissection (PLND) as measured by lymph node yield reduces biochemical recurrence (BCR) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa), stratified according to Briganti nomogram-derived risk (≥5

Introduction: Focal therapy has emerged as an alternate treatment for men with localized prostate cancer (PCa). Irreversible electroporation (IRE) is an available technique for focal ablation. IRE ablates prostate tissue by delivering direct current between electrodes placed transperineally into the prostate. During IRE a characteristic sign, which we propose to term the “Stricker Sign,” is noted in the ablation field. The sign appears as a hyperechoic ring formed between the electrodes on the periphery of the ablated area, while the PCa lesion within becomes hypoechoic. The presence of this event provides real-time feedback to the surgeon, indicating that the targeted lesion has been covered during ablation with an acceptable margin of benign tissue around the tumor. The ablation zone extents outside the needle configuration due to resulting spheric electrical field.1 Materials and Methods: Written patient consent obtained. Intraprocedural transrectal ultrasound imaging was performed on a 65-year-old man referred with a PSA of 6.71 ng/mL. His preprocedure multiparametric magnetic resonance imaging (mpMRI) demonstrated a prostate volume of 57.6 mL (PSA density 0.11 ng/mL2) and a 24 mm Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesion in the left peripheral zone at the apex. His prostate biopsy revealed Gleason 3 + 4 = 7 with 10% pattern 4 in 30% of material at the left midprostate. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography following biopsy revealed intense PSMA avidity in the posterolateral left peripheral zone at the prostatic apex, without metastatic disease. After thorough counseling, the patient elected focal therapy and proceeded to have irreversible electroporation (IRE) of the left apex using the Nanoknife® system. The technique for IRE has been previously published in detail.2,3 Results: Throughout the course of the procedure, as shown on ultrasound imaging, a characteristic sign is noted in the ablation field—the PCa lesion remains hypoechoic, while a hyperechoic ring forms as the current runs between/around the electrodes on the periphery of the ablated area. This assists in confirming that the region of interest has been successfully targeted. A MRI was performed 2 days after IRE to confirm the ablation covered the tumor location, overlapping the “Stricker sign.” The sign arises from the increased tissue density and reduced water content of PCa, compared to normal prostatic tissue. It has been well established that PCa has a different density and water content compared to normal prostatic tissue and results in restricted diffusion in mpMRI of the prostate.4,5 The hyperechoic ring is formed due to the comparatively high water content of the ablated benign tissue. As the electrical impulses are transmitted, electrolysis of water occurs which leads to production of hydrogen and oxygen gas. In contrast, PCa has a lower water content, and thus does not produce as much gas, leading to the progressively hypoechoic appearance. Conclusions: Currently, patients are required to have a repeat mpMRI within 1 week of the procedure to confirm the region of interest has been covered. Use ultrasound-guidance provides the surgeon with real-time feedback, immediately demonstrating ablation of the targeted lesion with a margin of benign tissue. Authors received/archived patient consent for video recording/publication in advance. M.J.S.: Angiodynamics Educational grant. P.D.S.: Angiodynamics paid consultant. Runtime of video: 3 mins 29 secs

Background: In active surveillance there is significant interest in whether imaging modalities such as multiparametric magnetic resonance imaging (mpMRI) or 68Gallium prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA-PET/CT) can improve the detection of progression to clinically significant prostate cancer (csPCa) and thus reduce the frequency of prostate biopsies and associated morbidity. Recent studies have demonstrated the value of mpMRI in active surveillance; however, mpMRI does miss a proportion of disease progression and thus alone cannot replace biopsy. To date, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown additive value to mpMRI in its ability to detect prostate cancer (PCa) in the primary diagnostic setting. Our objective is to evaluate the diagnostic utility of PSMA-PET to detect progression to csPCa in active surveillance patients.Methods: We will perform a prospective, cross-sectional, partially blinded, multicentre clinical trial evaluating the additive value of PSMA-PET with mpMRI against saturation transperineal template prostate biopsy. Two hundred and twenty-five men will be recruited who have newly diagnosed PCa which is suitable for active surveillance. Following enrolment, patients will undergo a PSMA-PET and mpMRI within 3 months of a repeat 12-month confirmatory biopsy. Patients who remain on active surveillance after confirmatory biopsy will then be planned to have a further mpMRI and PSMA-PET prior to a repeat biopsy in 3-4 years. The primary outcome is to assess the ability of PSMA-PET to detect or exclude significant malignancy on repeat biopsy. Secondary outcomes include (I) assess the comparative diagnostic accuracies of mpMRI and PSMA-PET alone [sensitivity/specificity/negative predictive value (NPV)/positive predictive value (PPV)] to detect progression on biopsy based on predefined histologic criteria for progression; (II) comparison of index lesion identification by template biopsies vs. MRI targeted lesions vs. PSMA targeted lesions; (III) evaluation of concordance of lesions identified on final histopathology and each imaging modality (PSMA-PET and/or mpMRI) in the subset of patients proceeding to RP. Discussion: The results of this trial will define the role of PSMA-PET in active surveillance and potentially reduce the number of biopsies needed to detect progression to csPCa.Trial Registration: The current trial was registered with the ANZCTR on the 3/2/2022 with the trial ID ACTRN12622000188730, it is accessible at https://www.anzctr.org.au/.

Abstract Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings. Cancer Res; 70(9); 3576–85. ©2010 AACR.

Supplementary Figure Legend from Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT). We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2–3. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥2, extracapsular extension >0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA-PET for csPCa (separate and combined) was calculated within a four-quadrant prostate model by receiver-operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi-ablative FT. In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA-PET to 0.84, 87%, 80%, 81% and 86%, respectively ( P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi-ablative FT. Addition of PSMA-PET correctly identified 26/46 (57%) non-suitable patients and resulted in 4/138 (3%) false-positive exclusions. Addition of PSMA-PET to the conventional work-up by mpMRI and systematic biopsies could improve selection for hemi-ablative FT and guide exclusion of patients for whom whole-gland treatments might be a more suitable treatment option.

To evaluate the safety, and short to mid‐term oncological and quality‐of‐life (QoL) outcomes of focal irreversible electroporation (IRE) for radio‐recurrent prostate cancer (PCa) at a median follow‐up of 4 years.

OBJECTIVES:To evaluate longer-term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow-up of 5 years (up to 10 years).PATIENTS AND METHODS:All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow-up were analysed. Follow-up included 6-month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate-specific antigen (PSA) levels. Failure-free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy.RESULTS:A total of 229 patients were analysed with a median (interquartile range [IQR]) follow-up of 60 (40-80) months. The median (IQR) age was 68 (64-74) years, the median (IQR) PSA level was 5.9 (4.1-8.2) ng/mL, and 86% harboured intermediate-risk disease and 7% high-risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17-53) months after IRE. Kaplan-Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis-free survival was 99.6% (228/229), PCa-specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow-up biopsy and MRI showed a complete ablation in 82% (186/226). Short-term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%).CONCLUSION:Longer-term follow-up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long-term follow-up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.

PURPOSE:This study aimed to assess the medium-term oncologic outcomes of an active surveillance protocol, replacing confirmatory biopsy with serial multiparametric magnetic resonance imaging. MATERIALS AND METHODS:A total of 172 men were enrolled in this single-arm prospective trial. Men with prostate cancer (Gleason 3+3=6 or Gleason 3+4=7 with ≤10% Gleason pattern 4 overall and <2 cores Gleason pattern 4) eligible for surveillance were included in the study. Men underwent baseline multiparametric magnetic resonance imaging and template ± targeted biopsy, then multiparametric magnetic resonance imaging at years 1 and 2 with a 3-year end-of-protocol biopsy. Biopsies during the 3-year protocol period were triggered by abnormalities on multiparametric magnetic resonance imaging and/or increases in prostate specific antigen density (>0.2 ng/ml/cc). RESULTS:The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric magnetic resonance imaging to detect progression to clinically significant prostate cancer were 57% (95% CI 39%-74%), 82% (95% CI 74%-89%), 50% (95% CI 38%-62%), and 86% (95% CI 81%-90%), respectively. Both multiparametric magnetic resonance imaging and prostate specific antigen density were significant predictors for progression (multiparametric magnetic resonance imaging OR 6.20, 95% CI 2.72-14.16, P < .001; prostate specific antigen density OR 6.19, 95% CI 2.14-17.92, P = .001). Only 2.3% (4/172) of patients had false-negative multiparametric magnetic resonance imaging and high-risk pathological features (pT3 or high-volume International Society of Urological Pathology >2). After a median 69 months (Q1-Q3 56-79) follow-up of all patients in the cohort, freedom from biochemical recurrence, metastasis, and prostate cancer-related death were 99.3%, 100%, and 100%, respectively. CONCLUSIONS:Final analysis of the Magnetic Resonance Imaging in Active Surveillance trial indicates that there is minimal risk to omitting 1-year confirmatory biopsy during active surveillance if baseline magnetic resonance-targeted + saturation template biopsy was performed; however, standardized 3-year systematic biopsy should be performed due to occasional magnetic resonance imaging-invisible tumors.

ObjectiveTo assess the predictive value of biopsy-identified cribriform carcinoma and/or intraductal carcinoma (CR/IDC) within the Briganti and MSKCC nomograms predicting lymph node metastasis (LNM) in patients with primary prostate cancer (PCa).MethodsWe retrospectively included 393 PCa patients who underwent radical prostatectomy with extended pelvic lymph node dissection at 3 tertiary referral centers. We externally validated 2 prediction tools: the Briganti 2012 nomogram and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Both nomograms were augmented with CR/IDC. The original model was compared with the CR/IDC-updated model using the likelihood ratio test. The performance of the prediction tools was assessed using calibration, discrimination, and clinical utility.ResultsOverall, 109 (28%) men were diagnosed with LNM. Calibration plots of the Briganti and MSKCC nomograms demonstrated an underestimation of the LNM risk across clinically relevant thresholds (≤15%). The addition of CR/IDC to the Briganti nomogram increased the fit of the data (χ2(1) = 4.30, P = .04), but did not improve the area under the curve (AUC) (0.69, 95% CI 0.63-0.75 vs 0.69, 95% CI 0.64-0.75). Incorporation of CR/IDC in the MSKCC nomogram resulted in an increased fit on the data (χ2(1) = 10.04, P <.01), but did not increase the AUC (0.66, 95% CI 0.60-0.72 vs 0.68, 95% CI 0.62-0.74). The addition of CR/IDC to the Briganti and MSKCC nomograms did not improve the clinical risk prediction.ConclusionIncorporation of CR/IDC into the 2 clinically most used pre-radical prostatectomy nomograms does not improve LNM prediction in a multinational, contemporary PCa cohort.