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Our objective is to determine the accuracy of multiparametric MRI (mpMRI) in predicting pathologic grade of prostate cancer (PCa) after radical prostatectomy (RP) using simple apparent diffusion coefficient metrics and, specifically, whether mpMRI can accurately separate disease into one of two risk categories (low vs. higher grade) or one of three risk categories (low, intermediate, or high grade) corresponding to the new prognostic grade group (PGG) criteria. This retrospective, HIPAA-compliant, IRB-approved study included 140 patients with PCa who underwent 3 T mpMRI with endorectal coil and transrectal ultrasound-guided (TRUS-G) biopsy before RP. MpMRI was used to classify lesions using a two-tier (low-grade/PGG 1 vs. high-grade/PGG 2–5) or a three-tier system (low-grade/PGG 1 vs. intermediate-grade/PGG 2 vs. high-grade/PGG 3–5). Accuracy of mpMRI was compared against RP for each system. The predictive accuracy of mpMRI using the two-tier system is higher than when using three-tier system (0.77 and 0.45, respectively). There were similar rates of undergrading between mpMRI and TRUS-G biopsy compared to RP (16% & 21%; respectively); rate of overgrading was higher for mpMRI vs. TRUS-G biopsy compared to RP (42% & 17%, respectively). When mpMRI and TRUS-G biopsy are combined, rate of undergrading is 1.4% and overgrading is 11%. MpMRI predictive accuracy is higher when using a two-tier vs. a three-tier system, suggesting that advanced metrics may be necessary to delineate intermediate- from high-grade disease. Rates of under- and overgrading decreased when mpMRI and TRUS-G biopsy are combined, suggesting that these techniques may be complementary in predicting tumor grade.

Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

To assess factors that affect prostate biopsy results following salvage whole gland cryoablation.One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χFifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy.Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

To compare the oncologic and functional outcomes of partial vs whole-gland cryotherapy for men with intermediate-risk prostate cancer.Men with intermediate-risk prostate cancer treated with primary prostate cryotherapy from 1993 to 2013 were selected from the Cryo On-Line Data Registry for a 1:1 matched comparison between those undergoing whole-gland and partial prostate cryotherapy (targeted ablation, unilateral/bilateral nerve-sparing ablations). A propensity score was developed based on age, prebiopsy serum prostate-specific antigen, biopsy Gleason score, clinical stage, prostate volume, neoadjuvant androgen deprivation status, year of surgery, and pretreatment potency. Outcomes were biochemical progression-free survival (BPFS) using the American Society for Therapeutic Radiation Oncology (ASTRO) and Phoenix criteria, 12-month continence (strictly pad free), and sexual function (potency sufficient for sexual intercourse). After propensity score matching, BPFS was compared using Kaplan-Meier analysis and functional outcomes using chi-square tests.In all, 897 men were identified (731 whole gland and 166 partial). Postmatching, 166 pairs of men were analyzed (mean follow-up 31 months). The 2/5-year BPFS rate was 87.2%/76.4% for whole-gland vs 80.7%/70.0% for partial ablation using Phoenix (p = 0.26) and 72.3%/69.6% for whole-gland vs 82.1%/75.0% for partial ablation using ASTRO criteria (p = 0.10). Of 164 pairs, the 12-month continence rate was similar, 94.1% vs 95.1% (p = 0.803). Of 139 pairs, the 12-month rate of effective intercourse was 29.5% for whole-gland and 46.8% for partial ablation (odds ratio 2.1, p = 0.003). The incidence of post-treatment urinary retention was 6.0% and 6.6% (p = 0.88) following whole-gland and partial ablation, respectively, and that of rectourethral fistula was 1.2% and 0% (p = 0.50).Partial ablation results in better post-treatment sexual function compared with whole-gland ablation in men with intermediate-risk prostate cancer. We did not observe a difference in early BPFS between the two groups.

Purpose: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). Methods: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. Results: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. Conclusions: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community., SCOPUS: ar.j, info:eu-repo/semantics/published

The majority of prostate-specific antigen (PSA) screen-detected prostate cancers are low grade and low stage, rendering them suitable for active surveillance in the low-risk group and for focal therapy of the intermediate-risk group with low-volume cancers. While the importance of prostate cancer varies between more developed and less developed countries in East and Southeast Asia due to competing causes of mortality and differential penetrance of PSA screening, there has been a general increase in the incidence of prostate cancer. Cultural differences in decision-making and the acceptance of gland-preserving strategies as well as geographic variability in the dissemination of advanced imaging, biopsy, and ablative technologies are also significant factors in the uptake of focal therapy and active surveillance in East and Southeast Asia. The currently published literature on active surveillance and focal therapy in Asia remains sparse. With an aging population and longer life expectancy due to improving healthcare, focal therapy and active surveillance will become increasingly important in the management of prostate cancer in Asia.

In an effort to achieve cancer control and yet minimize damage to these structures, the urological community has been exploring the idea of treating just a specific portion of the prostate where the cancer is located and actively monitoring the untreated portion of the gland. This approach is known as “focal therapy.” We believe that the best outcomes are achieved when an appropriate treatment is matched to a suitable patient based on individual circumstances and needs. We wrote this chapter as a resource to help patients better understand the concept of focal therapy, its benefits, possible side effects, and risks so as to aid them in making an individualized treatment decision for their cancer.

The concept of anterior cancer was recently defined as cancers located anterior to the posterior sectors/part of the prostate sampled by posterior systematic biopsies, i.e., at a distance of at least 17 mm (posterior biopsy core length) anterior to the rectal surface of the gland. Anterior cancers comprise peripheral zone (PZ) origin and transition zone (TZ) origin cancers. Their pattern of spread differs according to their PZ or TZ origin. In this chapter we will discuss only TZ origin cancers. We will first review their prevalence, pattern of spread, and diagnostic pathways. Then the rationale for focal therapy and approaches including surgical partial excision, thermal ablation, and radiation therapy will be discussed.

The prevalence of benign prostatic hyperplasia (BPH) increases with age, affecting more than 50% of men above the age of 50 to varying degrees. As it enlarges, it compresses onto the urethra causing bladder outlet obstruction. This can cause a spectrum of problems ranging from irritative and obstructive lower urinary tract symptoms (LUTS) to retention of urine with obstructive uropathy. Transurethral resection of prostate (TURP) is the standard for surgical intervention, however with the advent of an ageing population, there is an increasing number of patients who have ischaemic heart disease who require long-term anticoagulation and have multiple co-morbidities that put them at an increased risk of general anaesthesia. This review aims to critically appraise the effectiveness and evidence for use of these minimally invasive techniques. Both PubMed and Ovid were used to search for randomised control trials (RCT) comparing the various minimally invasive techniques against TURP. In cases where there were no RCTs, the results of the respective trial were compiled. This was later compiled in a summary table. An effective minimally invasive treatment modality will play a complimentary role to TURP which remains the standard of surgical treatment for BPH. Technologies progressing towards rapid re-creation of prostatic channel, minimal blood loss and non-urethral instrumentation will bridge the divide between pharmacotherapy and surgery.

47 Background: Large-scale genome-wide association studies have established germline polygenic risk loci that underpin the susceptibility to prostate cancer (PCa). However, most trials conducted are in men of European ancestry with data missing for Asian male PCa. Here, we report on an in-house multidimensional bioinformatics pipeline that integrates OMICS and non-OMICS approaches in identifying true germline risk-variants for PCa in Asian men. Methods: We utilized a prospective cohort study of Asian men who were newly diagnosed with PCa. Whole exome sequencing (Illumina Hiseq, CA) of blood (100X) was performed. The OMICS-based approach entailed a stepwise screen for hallmarks of cancer-specific pathways. A genome-proteome network was then developed to filter for known pathogenic variants; this was followed by comparison against a large artificial database of aggregated germline variants (N = 95,000) with reported linkage to PCa susceptibility. Finally, mutations were filtered through a non-OMICS pipeline that entailed data synchronization with population-level statistics and clinical outcomes (recurrence and survival). Results: Preliminary analyses were based on 277 PCa cases; of which 50 were M1 cases. Screening using a non-combined unbiased approach yielded 36,157 germline variants. This contrast against our OMICS-based approach, which reduced the variant calls to 6,144 significantly associated mutations. Next, by focusing on pathway-specific genes related to hormonal regulation and known cancer hotspot mutations, we could further tighten our variant calls to 3,562 hormone-related variants (rs9269958 on HLA-DRB1) and 2,125 variants in known cancer genes, notably (rs8176320 on BRCA1/2, rs2555691 on LILRA2, rs8036934 on TP53BP1). Conclusions: Here, we show that application of an OMICS approach that combines pathway-driven analyses and an artificial dataset, along with population-level statistics and clinical relevance resulted in more robust annotation of germline variants that were associated with PCa.

95 Background: There is limited data on clinical and patient-reported quality of life (PRO-QOL) outcomes after stereotactic body radiotherapy (SBRT) in Asian men with localised prostate cancer. Demographic differences with regard to PRO-QOL outcomes may be due to variation in germline genetics. We therefore conduct a single-institution prospective phase II trial of prostate SBRT in Asian men with intermediate-risk prostate cancers (IR-PCa). Additionally, we investigated association of dosimetric and genetic factors with outcomes. Methods: Patients with biopsy-proven NCCN-defined IR-PCa were recruited. SBRT was delivered at 36.25 Gy/5fr using a Linac-based RapidArc technique. Adverse events (AEs) were assessed with CTCAEv4.0 and IPSS; PRO-QOL assessed using the EPIC instrument at baseline, 1 and 2-year post-SBRT. Germline genetics were profiled by whole exome sequencing (30X). Results: 65 patients were recruited over the period of 2014-2016 (median follow-up = 30 mo). We observed 4 acute ≥G2 gastrointestinal (GI) events (3 fecal urgency, 1 diarrhea). Longitudinal assessment of acute genitourinary (GU) events by IPSS showed worsened symptoms that peaked at 1 wk post-SBRT (44.6% vs 6.2% at 1 mo for men reporting scale upgrade). There was no significant association between acute GU effects (by IPSS) and dosimetric parameters of the irradiated urethra and bladder. PRO-QOL scores demonstrated minimal change over time across all domains; however, sexual bother in the top 50th percentile subgroup at baseline indicated ≥20% worsening of scores for 10/32 (31%) at 12 mo and 5/12 (42%) at 24 mo; which was not associated with Dosemax to the penile bulb (P = 0.1). We observed a high frequency of germline mutations in DNA repair genes (N = 10; 15.4%), including two BRCA2 stop-gain and frameshift mutations. In particular, BRCA2 mutations were detected in 2 of 4 cases with ≥G2 GI effects, independent of rectal dose. Conclusions: While prostate SBRT is well tolerated in our Asian cohort, there appears to be demographic differences in sexual bother compared to Caucasian cohorts. Interestingly, we observed a higher than expected prevalence for germline mutations in DNA repair genes, which may predict treatment response. Clinical trial information: NCT02313298.

Objective Prostate cancers (PCa) in Asian individuals are molecularly distinct from those found in their Caucasian counterparts. There is no risk stratification tool for Asian men with rapid biochemical recurrence (BCR) following radical prostatectomy (RadP). This study aims to assess the detection rate of 68Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-RadP.Methods 68Ga PSMA-PET and CT body with/without bone scan [conventional workup (CWU)] were performed in 55 Asian patients with BCR within 36 months post-RadP. Two blinded reviewers assessed the images. Detection rates of 68Ga PSMA-PET/CT were evaluated, and impact on management was reviewed by comparison with CWU. Results Median time to BCR post-RadP was 8.1 months. Detection rate for 68Ga PSMA-PET/CT was 80% (44/55). A positive scan was significantly associated with increasing prostate-specific antigen (PSA) level [odds ratio (OR) = 1.13 (95% CI 1.05–1.30), P = 0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, 68Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44 (56.8%) patients: 10 to hormonal therapy (HT) and whole pelvis radiotherapy (RT) in addition to bed RT, and 15 to palliative HT alone. Conclusions In the present report, we demonstrated the diagnostic and treatment decision utility of 68Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels (< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

Purpose of review Progress in imaging, fusion software, and ablative modalities has fostered growth of the latest image-guided generation of high-intensity focused ultrasound (HIFU) for focal treatment of prostate cancer. Although early reports are encouraging, important questions remain regarding candidate selection, treatment, and outcomes. We review contemporary considerations for the use of HIFU for focal treatment of primary and radio-recurrent prostate cancer. Recent findings HIFU has been used to treat prostate cancer for over two decades. More recently, stage migration from screening and improvements in pelvic imaging and fusion technology has resulted in wider clinical application of focal HIFU as a first-line treatment for localized prostate cancer. Advanced imaging has also improved targeting for focal salvage therapy of radio-recurrent disease. Proponents point to the minimally invasive nature, limited morbidity profile, and ability to perform retreatments in the future. Critics emphasize positive post-treatment biopsies, nonuniform treatment protocols, and absence of long-term follow-up. Thus, a review of clinical considerations and recently published data is warranted. Summary Recent advances have strengthened support for the use of focal HIFU. Although HIFU has great potential, it must be applied judiciously, maintaining appropriate oncologic principles in the setting of standardized trials to determine its true clinical value.

Purpose To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). Methods A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. Results Consensus was attained on 23 of 27 topics; TargetedFT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. Conclusion Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice. Electronic supplementary material The online version of this article (doi:10.1007/s00345-016-1782-x) contains supplementary material, which is available to authorized users.

Objective To evaluate the diagnostic properties of multiparametric magnetic resonance imaging in the detection, localization and characterization of prostate cancer using three-dimensional transperineal template mapping biopsy histopathology as the comparator. Methods A retrospective analysis of patients undergoing prostate multiparametric magnetic resonance imaging followed by three-dimensional transperineal template mapping biopsy was carried out. For imaging and pathology data, the prostate was divided in octants with the urethra being the midline. The index test properties were calculated using the biopsy histopathology as the reference test with the following end-points: any cancer, any Gleason ≥7, any Gleason ≥7 or cancer length of ≥4 mm and any Gleason ≥7 or 6 mm in any given core. The latter two definitions correspond to 0.2 and 0.5 mL of cancer volume, respectively. Diagnostic properties including sensitivity, specificity, positive and negative predictive values were calculated. Results A total of 50 patients were included in the study. A median of 55 (interquartile range 42–63) biopsy cores were obtained per patient. Of 400 prostate octants evaluated, 28.5% had prostate cancer on mapping biopsy, whereas 23% of octants were considered suspicious for cancer on imaging. Multiparametric magnetic resonance imaging negative predictive values for Gleason ≥7 and clinically significant cancers were 84–100%. Similarly, specificity ranged between 79% and 85%. Sensitivity and positive predictive value remained moderate for all the reference test definitions. Conclusions Multiparametric magnetic resonance imaging is a useful minimally-invasive tool for detection, localization and characterization of prostate cancer. This imaging modality has high negative predictive value and specificity, and therefore it could be used to reliably rule out clinically significant cancer, obviating the multicore mapping biopsy.

The purpose of this study is to investigate the accuracy of multiparametric MRI with endorectal coil and Partin tables in predicting organ-confined (OC) prostate cancer in a contemporary cohort undergoing radical prostatectomy (RP) and to assess the possible added value of radiologic staging based on multiparametric MRI to the predictive accuracy of Partin tables.One hundred fifty-eight consecutive subjects underwent 3-T multiparametric MRI with endorectal coil before RP between November 2010 and November 2013. Data were randomly split 60% and 40% into derivation (n = 95) and validation (n = 62) datasets. Multiparametric MRI was used to assess the radiologic stage, and logistic regression models were created using the derivation dataset and were fit on the independent validation dataset using multiparametric MRI staging alone and with prostate-specific antigen (PSA) level as the covariate. The probability of each patient to harbor OC disease was calculated using an updated version of Partin tables, using either clinical staging from digital rectal examination (DRE) or radiologic staging (multiparametric MRI). The AUC was calculated to evaluate accuracy of these predictive methods.The accuracy of multiparametric MRI to predict OC disease on pathologic analysis was greater (AUC, 0.88) than that of Partin tables (AUC, 0.70) and improved when multiparametric MRI was combined with PSA level (AUC, 0.91). The accuracy of Partin nomograms to predict OC disease decreased (AUC, 0.63) when staging was based on multiparametric MRI versus DRE.The superior predictive accuracy of multiparametric MRI compared with Partin tables to predict OC disease validates the results of smaller previously published studies. Although there is no added benefit of substituting multiparametric MRI stage for clinical stage when using Partin tables, multiparametric MRI staging information is valuable as a stand-alone test.

INTRODUCTION AND OBJECTIVES: The incidence of renal masses has been increasing steadily in recent years, in part due to the widespread use of cross sectional imaging. Interestingly, the prevalence of obesity is on the rise as well suggesting a potential link between the two trends. In the present study we aim to investigate the potential association between BMI and clinico-pathological features of localized renal masses. METHODS: An international, multi-institutional retrospective review of patients that underwent surgery for clinically localized renal masses between 2000 and 2010 was undertaken following an IRB approval. Patients were divided into four BMI groups: A (BMI

377 Background: In patients with biochemical relapse (BCR) following radical prostatectomy (RadP), risk stratification by clinical indices alone is suboptimal for identifying subgroups likely to benefit from salvage radiotherapy (RT). It is also recommended that combination hormonal therapy (HT)-RT improves rates of salvage and survival, hence the need for a clinical tool to better stratify patients for RT and HT-RT; the latter approach for patients at risk of occult metastases. Herein, we investigated the role of 68Ga-Prostate-specific Membrane Antigen (PSMA)-PET in the detection of regional and distal recurrences, and for clinical decision making in a prospective cohort of patients with BCR post-RadP. Methods: 68Ga-PSMA-PET and CT were performed in a cohort of 50 RadP patients with BCR. Radiological interpretation was independently performed by two assessors, who were blinded to the patient identifiers. PSMA+ lesions were considered as true positives; negative-PSMA in the presence of continued PSA rise defined false negative. Impact on clinical decision making was reviewed by comparison of PSMA-PET and CT findings in the post-RadP PSA 0.5-2.0 ng/ml subgroup. Results: Overall detection rate for 68Ga-PSMA/PET was 74% (37 of 50) in our cohort with a median post-RadP PSA level of 2.19 (IQR = 0.45-4.26). Detection rates were significantly increased at a PSA cut-off > 1.0; 96% (25 of 26) at > 2.0 and 100% (5 of 5) at 1.0-2.0 compared to 67% (4 of 6) at 0.5-1.0, and 23% (3 of 13) at < 0.5 (P < 0.001). In 0.5-2.0 PSA subgroup, 3 regional nodes and 11 distal (6 nodes, 4 bones, 1 lung) lesions were detected. This altered treatment in 5 of the 11 (46%) cases; 3 N+ cases would have been recommended for HT-RT and pelvic nodal RT, while RT would be omitted in 2 patients due to low volume systemic disease. Conclusions: Our findings support the existing data for PSMA-PET as a sensitive diagnostic tool for clinical recurrences post-RadP. Additionally, the detection of small volume nodal and distal lesions at post-RadP PSA levels of < 2.0 ng/ml highlights the potential utility of PSMA-PET for selecting patients to treatment intensification with HT-RT or omission of RT in cases of distal relapse.

Multi-parametric MRI (mpMRI) is widely used in the detection and characterization of clinically- significant prostate cancer. MRI-TRUS (trans-rectal ultrasound) fusion biopsy is an in-office procedure that promises to empower urologists to successfully target these MRI-visible lesions for histological confirmation. We describe the moving parts in the process and discuss methods to optimize biopsy outcomes. mpMRI is highly technical and reader-dependent. The acquisition of US images to generate a valid 3D US model and subsequent registration and fusion requires the urologist to attain equilibrium of probe position and pressure to achieve maximum registration accuracy. Environmental, medical and engineering measures can be undertaken to improve targeting accuracy. The art and skill of 'hitting' a visual target involves real-time recognition and adjustment for potential errors/ mis-registration in the fusion guide. A multi-disciplinary team effort is critical to improve all steps of the procedure.

INTRODUCTION AND OBJECTIVES: In low-risk prostate cancer, we investigate if a strategy of combination staging-biopsy (CSB) of robotic transperineal saturation biopsy (rTPB) and MRI-targeted biopsy (MRI-TB) better classifies these patients for treatment options. METHODS: This IRB-approved, prospective study included men with low-risk prostate cancer (PSA of 10 ng/ml, Gleason score 6, clinically T2a) diagnosed on conventional transrectal ultrasoundguided (TRUS) biopsy. Patients first underwent multiparametric-MRI of the prostate 6 weeks after initial TRUS biopsy. A single dedicated radiologist then marked and assigned a PIRADS score to each suspicious lesion on a 24-sector template grid of the prostate. Biopsies were performed via transperineal route under general anaesthesia with iSR’obot Mona Lisa, a robotic platform with maximal coverage of prostate using realtime 3D-ultrasound technology. Systematic rTPB was first performed by a surgeon blinded to the MRI findings. Next, the MRI positive sector was targeted with 6 biopsy cores by a second surgeon. Our primary outcome was upgrading of Gleason score at CSB compared to initial TRUS biopsy. The secondary outcome was proportion of upgrading at MRI-TB compared to rTPB. RESULTS: The 15 Singaporean men included have a mean age of 65.5 years. The mean PSA at diagnosis was 6.6 2.0 ng/ml and the mean prostate volume was 32.1 13.4 cc. At rTPB, a mean of 26.5 9.1 cores were taken per patient, with a mean biopsy intensity of 0.87 0.17 cores/ml of prostate. A total of 52 sectors were positive on MRI, of which 17 were PIRADS 5, 23 were PIRADS 4 and 12 were PIRADS 3. On MRI-TB, 14 lesions were Gleason 7 and all were PIRADS 5. Overall, CSB up-classify 5 patients (33.3%) 2 by MRI-TB alone, 1 by rTPB alone and 2 by both modalities. CONCLUSIONS: CSB upgrades a third of our patients presumed to be low-risk by initial TRUS biopsy. MR-TB detects 80 % of these patients. In patient with PIRADS 5 score, MRI-TB detects all Gleason 7 cancers. Source of Funding: none

Upper-tract urothelial carcinoma (UTUC) is a rare disease that tends to present late and at a muscle-invasive stage in comparison to its lower-tract counterpart [1]. To compound matters, patients with UTUC are usually smokers and older, and have multiple comorbidities, often including significant renal impairment. While immediate postoperative instillation and neoadjuvant systemic chemotherapy have become the standard of care for lower-tract urothelial cancers, these remain difficult to apply in patients with UTUC [2]. Furthermore, the development of prognostic tools that could help in selecting patients for these therapies has been challenging. Thus, it is timely that Tanaka and colleagues [3], through a multicenter collaborative effort, propose a new marker score as a prognostic tool for UTUC. Virchow first noted the connection between inflammation and cancer when he observed the presence of a ‘‘lymphoreticular infiltrate’’ in cancers arising at sites of chronic inflammation [4]. The concept of inflammation as a critical component of tumor progression has since been expanded with the recognition of inflammatory cells as orchestrators of the tumor microenvironment [5]. In an attempt to elucidate the role of inflammation in UTUC outcomes, the authors have laudably built on previous work identifying C-reactive protein (CRP) as a prognostic marker, and combine those findings with the neutrophil/ lymphocyte ratio (NLR) and plasma fibrinogen levels, markers identified in European patients [6,7]. Although this is a step in the right direction, the scientific approach used in the study warrants discussion and the results should interpreted in context.

In this paper, we proposed a new method (CSR+OSD) for the extraction of irregular open prostate boundaries in noisy extracorporeal ultrasound image. First, cascaded shape regression (CSR) is used to locate the position of prostate boundary in the images. In CSR, a sequence of random fern predictors are trained in a boosted regression manner, using shape-indexed features to achieve invariance against position variations of prostate boundaries. Afterwards, we adopt optimal surface detection (OSD) to refine the prostate boundary segments across 3D sections globally and efficiently. The proposed method is tested on 162 ECUS images acquired from 8 patients with benign prostate hyperplasia. The method yields a Root Mean Square Distance of 2.11±1.72 mm and a Mean Absolute Distance of 1.61±1.26 mm, which are lower than those of JFilament, an open active contour algorithm and Chan-Vese region based level set model, respectively.

Automatic segmentation of the prostate zones has great potential of improving the accuracy of lesion detection during the image-guided prostate interventions. In this paper, we present a novel compact method to segment the prostate and its zones using multi-parametric magnetic resonance imaging (MRI) and the anatomical priors. The proposed method comprises of a prostate tissue representation using Gaussian mixture model (GMM), a prostate localization using the mean shift with the kernel of the prostate atlas and a prostate partition using the probabilistic valley between zones. The proposed method was tested on four sets of multi-parametric MRIs. The average Dice coefficient resulted from the segmentation of the prostate is 0.80 ± 0.03, the central zone 0.83 ± 0.04, and the peripheral zone 0.52 ± 0.09. The average computing time of the online segmentation is 1 min and 10 s per datasets on a PC with 2.4 GHz and 4.0 GB RAM. The proposed method is fast and has the potential to be used in clinical practices.

We aimed to identify a prostate cancer DNA hypermethylation microarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. This is a non-randomized retrospective study in 111 local Asian men (87 prostate cancers and 24 BPH) treated from 1995 to 2009 in our institution. Archival prostate epithelia were laser-capture microdissected and genomic DNA extracted and bisulfite-converted. Samples were profiled using Illumina GoldenGate Methylation microarray, with raw data processed by GenomeStudio. A classification model was generated using support vector machine, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset which yielded cancer detection sensitivity and specificity of 95.3% and 100% respectively, with overall accuracy of 96.4%. Second validation on another independent western cohort yielded 89.8% sensitivity and 66.7% specificity, with overall accuracy of 88.7%. A PHYMA score was developed for each sample based on the state of methylation in the PHYMA signature. Increasing PHYMA score was significantly associated with higher Gleason score and Gleason primary grade. Men with higher PHYMA scores have poorer survival on univariate (p = 0.0038, HR = 3.89) and multivariate analyses when controlled for (i) clinical stage (p = 0.055, HR = 2.57), and (ii) clinical stage and Gleason score (p = 0.043, HR = 2.61). We further performed bisulfite genomic sequencing on 2 relatively unknown genes to demonstrate robustness of the assay results. PHYMA is thus a signature with high sensitivity and specificity for discriminating tumors from BPH, and has a potential role in early detection and in predicting survival.

the bladder neck. In relation to existing focal therapy literature, these outcomes are comparable in terms of potency (54–100%) and slightly lower in terms of continence (95–100%) but slightly higher in terms of urethral stricture (0–5%) [4]. Some physicians may claim that the results in this study are promising, whereas others may claim they are not ideal. The authors’ state that they did not enrich the cohort with patients who had optimal functional status prior to focal therapy, perhaps explaining why the functional outcomes were not so laudable. We also do not know the details of the index lesion location of the treatment, which can largely affect functional outcomes. Urinary and erectile outcomes are largely dependent on the patient’s baseline functional status along with the location of the treatment zone. Men who present with better function are more likely to maintain it. Conversely, men

Introduction: Cultural influences affect attitudes towards cancer screening, diagnosis, treatment and palliation. The objective of this study is to survey the prevailing attitudes towards cancer in a multicultural tertiary outpatient setting. Materials and Methods: This is a cross-sectional study of 300 respondents visiting the Singapore General Hospital (SGH) Urology Centre over a period of 1 month. A questionnaire was developed assessing responses to various facets of cancer management and administered in English, Chinese or Malay to every 10th person visiting the centre. Institutional review board approval was obtained. Results: Of 300 respondents, 57% were Chinese, 17% Malay, 19% Indian, and 7% others. Mean age was 54.3 years. Most respondents were male (68%) and had up to secondary education (56%). Most Chinese were Taoist/Buddhist (42%) or Christian/Catholic (36%) while Indians were largely Hindu (47%) or Muslim (27%). Thirty-seven percent of respondents had ever participated in cancer screening. Eighty-nine percent of respondents wanted to be the first to know if they had cancer, and 76% found it unacceptable if the diagnosis of cancer was withheld from them. These were irrespective of race, religion or other factors. Forty percent of respondents believed that being diagnosed with cancer was a matter of fate. Sixty percent of respondents would undergo treatment with 50% chance of cure, even if it involved major surgery and adjuvant therapy. Eighty-one percent believed in efficacy of at least 1 form of alternative treatment. Seventy-one percent of respondents preferred to die at home and this was most marked among Malay respondents (90.4%). Conclusion: This better understanding of patient attitudes will allow us to help patients balance wishes for autonomy versus family involvement in dealing with cancer. This will help us achieve a more holistic and patient-centred approach to cancer care. Key words: Attitude, Autonomy, Confidentiality, Culture

Objectives We previously reported a clinical trial in which we were unable to replicate the excellent diagnostic metrics produced in the developmental study of the TWIST1 and NID2 gene methylation assay. In this expanded trial with subjects enrolled from another institution, we reexamine the diagnostic capabilities of the test to externally validate our previous study. Materials and methods TWIST1 and NID2 gene methylation was assessed in DNA isolated from the urine of subjects at risk of bladder cancer undergoing cystoscopy for hematuria or bladder cancer surveillance. The diagnostic gold standard was cystoscopy. Two thresholds of TWIST1 and NID2 gene methylation were used for determining test result positivity, those published by Renard et al. and Abern et al. The sensitivity, specificity, positive and negative predictive values, diagnostic likelihood ratios, and receiver operating characteristic curves were calculated for each gene, as well as their combination. In all, 3 methods were used to combine TWIST1 and NID2 into a single composite test: (1) believe-the-positive decision rule — if either gene is methylated the test result is positive, which maximizes test sensitivity; (2) believe-the-negative decision rule — if either gene is not methylated the test result is negative, which maximizes test specificity; and (3) a likelihood-based logistic regression model approach that balances sensitivity and specificity. Clinical utility was determined using a decision curve analysis. Results A total of 209 subjects were evaluated: 40% for hematuria and 60% for bladder cancer surveillance. Approximately 75% were male, most of the prior cancers being low-grade Ta. Using cystoscopy as the gold standard, areas under the curve were 0.67 for TWIST1, 0.64 for NID2, and 0.66 for combined TWIST1 and NID2. Decision rule results revealed optimization of sensitivity at 67% using Renard thresholds and specificity using the Abern thresholds at 69%. We found improved sensitivity (78%) in current smokers. Decision curve analyses revealed that the methylation assay provided only a modest benefit even at high probabilities of missed cancer. Conclusion A urine DNA test measuring TWIST1 and NID2 methylation was externally examined with a larger cohort and its results continue to be poor. These 2 biomarkers are unlikely to replace cystoscopy, but they may be worthy of study in active smokers.

Objective . To determine the role of spouse's cigarette smoking in the detection of high-grade squamous intraepithelial lesions of the cervix. Design . Prospective cohort study with multivariate analysis. Setting . Colposcopy clinic in a tertiary hospital. Participants . Women referred to a colposcopy clinic for evaluation of abnormal Papanicolaou smears showing either repeated inflammatory changes, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Data collection . The women were interviewed with a structured questionnaire for sexual history, use of oral contraceptive pills, personal and spouse cigarette-smoking history, and obstetric history. Results . There were 623 women in the cohort. They were grouped into normal, LSIL, and HSIL categories based on colposcopy and histologic assessment. There were very few women who had had more than one sexual partner or a history of sexually transmitted diseases (STDs). The prevalence of oral contraceptive pill usage was 2.9% among the women in the normal group, 4.3% in women with LSIL, and 5.1% in women with HSIL. The incidence of cigarette smoking by the women was 2.5%, 3.2%, and 6.8% for the three groups of women, respectively. The incidence of spouse cigarette smoking was 25%, 35%, and 43% respectively. Compared to women in the normal group, women with HSIL were younger at first sexual intercourse, more likely to smoke cigarettes, and have spouses who smoked cigarettes. After controlling for age, age at first sexual intercourse, usage of combined contraceptive pills, and the woman's own cigarette-smoking habit, the odds ratio for HSIL was 1.046 for every stick of cigarette smoked by the spouse. In other words, the risk of detection of HSIL increased by 4.6% for every stick of cigarette her spouse smoked. Conclusion . Among women attending a colposcopy clinic, the risk of detection of HSIL increases with the spouse's cigarette-smoking habit. Further studies are warranted in quantifying the risk in a general population.