Surveillance one year post focal cryotherapy for clinically significant prostate cancer using mpMRI and PIRADS v2.1: An initial experience from a prospective phase II mandatory biopsy study.

Objectives: Multiparametric magnetic resonance imaging (mpMRI) surveillance post focal cryotherapy (FT) of prostate cancer is challenging as post treatment artefacts alter mpMRI findings. In this initial experience, we assessed diagnostic performance of mpMRI in detecting clinically significant prostate cancer (csPCa) after FT. Materials and methods: This single-centre phase II prospective clinical trial recruited 28 men with localized csPCa for FT between October 2019 and April 2021. 12-months post FT mpMRI were performed prior to biopsy and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of all mpMRI positive subjects were analysed. Chi square goodness of fit test correlated biopsy positive PIRADS3 (P3) and PIRADS4/5 lesions with histology grade group. One way ANOVA test assessed performance of ADC values in differentiating csPCa, non csPCa and benign lesions. Results: Sensitivity, specificity, PPV and NPV of mpMRI were 100%, 14.28%, 53.84% and 100% for subjects with histologically proven cancer. Correlation of PIRADS v2.1 scores with histologically proven prostate cancer was statistically significant (p < 0.5). Correlation of P3 lesions with non-csPCa was statistically significant (p < 0.02535). Higher ADC value was associated with benign histology (adjusted odds ratio OR 0.97, 95% confidence interval: 0.94, 0.99) (p = 0.008). Among the malignant lesions, higher ADC value was associated with non-csPCa (adjusted OR: 0.97; 95% CI: 0.95, 0.99) (p = 0.032). Conclusion: mpMRI is highly sensitive in detecting residual cancer. ADC values and PIRADS scores may be of value in differentiating csPCa from non-csPCa with a potential for risk stratification of men requiring re-biopsy versus non-invasive surveillance of remnant prostate.

Robot-assisted Magnetic Resonance Imaging-ultrasound Fusion Transperineal Targeted Biopsy.

OBJECTIVE: To demonstrate the key steps to perform robot-assisted magnetic resonance imaging-ultrasound fusion transperineal prostate biopsy. MATERIALS AND METHODS: Men with suspicion of prostate cancer underwent 3-Tesla multi-parametric MRI and were assigned a Prostate Imaging Reporting and Data System v2 score (PI-RADS). The prostate outline and suspicious lesions were marked by our radiologist using our software to produce a 3-dimensional prostate MRI model. All biopsies were performed under general anaesthesia and the real-time transrectal ultrasound model is created and subsequently fused with the MRI model using non-rigid software fusion. Transperineal targeted and systematic biopsy were then performed under stereotactic guidance using our robot-assisted prostate biopsy platform. Our clinically significant prostate cancer (Grade group ≥2) detection rates were previously described.1 RESULTS: Out of the 433 patients who underwent targeted and systematic biopsy, clinically-significant cancer detection rate was 46% (85% for PI- RADS 5 vs 38% for PI-RADS 4 vs 16% for PI-RADS 3; P < .001). Our overall complication rate was 13%, out of which the majority were Clavien-Dindo I (99%). The most common complications encountered were urinary retention (10%) and significant gross hematuria requiring bladder irrigation (2%). A higher prostate volume was associated with greater odds of urinary retention (OR 1.4, 95% CI: 1.21-1.65, P < .001 for every 10 mL increase in prostate volume). There was only 1 reported case of mild urinary tract infection. CONCLUSION: Robot-assisted transperineal prostate biopsy has established itself as a reliable and accurate method of prostate cancer detection with minimal morbidity.

Limitations of overlapping cores in systematic and MRI-US fusion biopsy.

OBJECTIVES: To evaluate the clinically-significant prostate cancer (csCaP) detection rate of systematic (SBx) vs. targeted biopsy (TBx), after accounting for the overlapping systematic cores within the MRI regions of interest. MATERIALS AND METHODS: We identified 398 consecutive men who underwent both transperineal systematic and targeted biopsy between January 2015 to January 2019. We reclassified overlapping systematic cores in the MRI regions of interest as target cores. The detection rates of SBx and TBx were compared using McNemar's test. RESULTS: Detection rate of csCaP (grade group ≥2) was 42% (168/398). Median number of systematic and targeted cores were 23 (IQR 19-29) and 9 (IQR 6-12) respectively. A median of 3 (IQR 2-4) overlapping systematic cores were reclassified as targeted cores. After accounting for overlap, csPC detection rate on SBx decreased from 37% and 21% while the csCaP detection rate of TBx increased from 34% to 39% (both P < 0.001), with TBx having a better detection rate (39% vs. 21%, P < 0.001). A previous negative biopsy was associated with a lower risk of having csCaP on non-targeted SBx (OR 0.27, 95% CI: 0.12 - 0.58, P = 0.001). Only 5% (13/243) of those who had no cancer detected on TBx had csCaP on non-targeted SBx compared to 45% (70/155) of those who had csCaP on TBx (P< 0.001). CONCLUSIONS: The utility of SBx in detecting csCaP decreases after accounting for overlap into the MRI region of interest, especially in men with a prior negative biopsy. Overlapping systematic cores improve the csCaP detection rate on TBx.

External validation and comparison of magnetic resonance imaging-based predictive models for clinically significant prostate cancer.

PURPOSE: Several multiparametric magnetic resonance imaging (mpMRI)-based models have been developed with significant improvements in diagnostic accuracy for clinically significant prostate cancer (csCaP), but lack proper external validation. We therefore sought to externally validate and compare all published mpMRI-based csCaP risk prediction models in an independent Asian population. PATIENTS AND METHODS: A total of 449 men undergoing combined transperineal fusion-targeted/systematic prostate biopsy at our specialist center between 2015 to 2019 were retrospectively analyzed. csCaP was defined as lesions with ISUP (International Society of Urological Pathology) grade group ≥2. The performance of 6 mpMRI-based risk models (MRI-ERSPC-3/4, Distler, Radtke, Mehralivand, van Leeuwen and He) were evaluated in terms of discrimination, calibration and clinical utility, using area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analyses. RESULTS: A total of 202 (45%) subjects were diagnosed with csCaP. All models demonstrated excellent accuracy with AUCs ranging from 0.75 to 0.86, and most significantly outperformed mpMRI PIRADSv2.0 (Prostate Imaging Reporting and Data System version 2.0) alone. The models by Mehralivand and He showed good calibration to our validation population, with respective intercepts of -0.08 and -0.84. All models were nevertheless recalibrated to the csCaP prevalence in our population for analysis. Decision curve analysis showed that above a threshold probability of 10%, all mpMRI-based models demonstrated superior net benefit compared to mpMRI PIRADSv2.0 or a biopsy-all-men strategy. The van Leeuwen model had the greatest net benefit, avoiding 39% of unnecessary biopsies while missing only 4% of csCaP, at a threshold probability of 15%. CONCLUSIONS: The mpMRI-based risk models demonstrate excellent discrimination and clinical utility and are easy to apply in practice, suggesting that individualized risk-based approaches can be considered over mpMRI alone to avoid unnecessary biopsies.

Comparative study of surgical orchidectomy and medical castration in treatment efficacy, adverse effects and cost based on a large prospective metastatic prostate cancer registry.

INTRODUCTION: Androgen deprivation therapy (ADT) remains the mainstay of treatment for metastatic prostate cancer (mPCa) but is associated with significant morbidities. Comparisons of medical castration (MC) and surgical orchidectomy (SO) have yielded varied results. We aimed to evaluate the oncological outcomes, adverse effect (AE) profiles and costs of MC and SO in patients with mPCa. METHODS AND MATERIALS: We reviewed 523 patients who presented with de novo mPCa from a prospectively maintained prostate cancer database over 15 years (2001-2015). All patients received ADT (either MC or SO) within 3 months of diagnosis. The data were analyzed with chi-square, binary and logistics regression models. RESULTS: One hundred and fifty one (28.9%) patients received SO while 372 (71.1%) patients had MC. The median age of presentation was 73 [67 -79] years old. The median prostate-specific antigen (PSA) was 280ng/ml [82.4-958]. Three hundred and thirty one patients (66.3%) had high volume bone metastasis and 57 patients (10.9%) had visceral metastasis. Clinical demographics and clinicopathological were similar across both groups. Similar oncological outcomes were observed in both groups. The proportion of PSA response (PSA <1ng/ml) was 65.6% for SO and 67.2% for MC (P = 0.212). Both therapies achieve >95% of effective androgen suppression (testosterone <50ng/dL). Time to castrate-resistance was similar (18 vs 16 months, P = 0.097), with comparative overall survival (42 vs. 38.5 months, P = 0.058) and prostate cancer mortality (80.1 vs. 75.9%, P = 0.328). Similarly, no difference was observed for the 4 AE profiles between SO and MC respectively; change in Haemoglobin (-0.75 vs. -1.0g/dL, P = 0.302), newly diagnosed Diabetes mellitus (4.6 vs. 2.9%, P = 0.281), control measured by HbA1c (0.2 vs. 0.25%, P = 0.769), coronary artery disease events (9.9 vs. 12.9%, P = 0.376) and skeletal-related fractures (9.3 vs. 7.3%, P = 0.476). After adjusting for varying governmental subsidies and inflation rates, the median cost of SO was $5275, compared to MC of $9185.80. CONCLUSION: Both SO and MC have similar oncological outcomes and AE profiles. However, SO remains a much more cost-effective form of ADT for the long-term treatment of mPCa patients.

Mutation signatures implicate aristolochic acid in bladder cancer development.

BACKGROUND: Aristolochic acid (AA) is a natural compound found in many plants of the Aristolochia genus, and these plants are widely used in traditional medicines for numerous conditions and for weight loss. Previous work has connected AA-mutagenesis to upper-tract urothelial cell carcinomas and hepatocellular carcinomas. We hypothesize that AA may also contribute to bladder cancer. METHODS: Here, we investigated the involvement of AA-mutagenesis in bladder cancer by sequencing bladder tumor genomes from two patients with known exposure to AA. After detecting strong mutational signatures of AA exposure in these tumors, we exome-sequenced and analyzed an additional 11 bladder tumors and analyzed publicly available somatic mutation data from a further 336 bladder tumors. RESULTS: The somatic mutations in the bladder tumors from the two patients with known AA exposure showed overwhelming AA signatures. We also detected evidence of AA exposure in 1 out of 11 bladder tumors from Singapore and in 3 out of 99 bladder tumors from China. In addition, 1 out of 194 bladder tumors from North America showed a pattern of mutations that might have resulted from exposure to an unknown mutagen with a heretofore undescribed pattern of A > T mutations. Besides the signature of AA exposure, the bladder tumors also showed the CpG > TpG and activated-APOBEC signatures, which have been previously reported in bladder cancer. CONCLUSIONS: This study demonstrates the utility of inferring mutagenic exposures from somatic mutation spectra. Moreover, AA exposure in bladder cancer appears to be more pervasive in the East, where traditional herbal medicine is more widely used. More broadly, our results suggest that AA exposure is more extensive than previously thought both in terms of populations at risk and in terms of types of cancers involved. This appears to be an important public health issue that should be addressed by further investigation and by primary prevention through regulation and education. In addition to opportunities for primary prevention, knowledge of AA exposure would provide opportunities for secondary prevention in the form of intensified screening of patients with known or suspected AA exposure.