Innovative standardized reporting template for prostate mpMRI improves clarity and confidence in the report.

PURPOSE: The goal of the current study was to evaluate the effect of a standardized prostate mpMRI reporting template on urologists' understanding and confidence in counselling a patient on the results of the MRI. To do this we performed a survey study to assess the understanding and confidence of urologists reviewing reports prior to (pre) and after (post) adoption of a standardized mpMRI template. METHODS: Six urologists reviewed ten pre- and post- mpMRI templated reports and completed a survey to assess the clarity of key elements and the confidence in counseling the patient. The urologists were blinded to the study objective. Nonparametric constrained permutation test for significance was performed to compare the results prior to and after implementation of the template. RESULTS: 29 pre- and 30 post-template mpMRI reports were reviewed. The average score for the post-template reports was significantly higher (10.7 ± 0.6 vs 7.5 ± 2.7 [ p< 0.001]) regardless of the reviewer. Urologists were also overall more confident in counselling patients when the standardized mpMRI reporting template had been used. CONCLUSION: Implementation of a standardized template for reporting of prostate mpMRI findings resulted in improved clarity and confidence in counselling patients. Radiologists should consider implementing a standardized reporting template to improve clinicians' understanding and confidence of the report.

Impact of mandated prospectively reported apparent diffusion coefficient values on the rates of positivity for clinically significant prostate cancer by PI-RADS score.

BACKGROUND: Prior research has shown that retrospectively measured apparent diffusion coefficient (ADC) of prostate magnetic resonance imaging (MRI) lesions is associated with clinically significant prostate cancer (csPCa) on targeted biopsy suggesting that ADC should be measured and reported prospectively. PURPOSE: To assess the impact of mandatory prospective measurement of ADC on the rates of positivity across PI-RADS scores for csPCa. MATERIAL AND METHODS: Consecutive patients who underwent ultrasound (US)-MRI fusion prostate biopsy from August 2018 to July 2019 and who had prospectively reported ADC were compared to control patients who did not. Rates of positivity by PI-RADS category were computed and compared using Chi-square. Multivariable regression was performed. RESULTS: In total, 126 patients (median age 65 years) with 165 prostate lesions (19, 51, 70, and 25 PI-RADS 2, 3, 4, and 5, respectively) and prospectively reported ADC values were compared to 113 control patients (median age 66 years) with 157 prostate lesions (17, 42, 64, and 34 PI-RADS 2, 3, 4, and 5, respectively). Rates of positivity across PI-RADS scores were similar between the two cohorts; 11%, 25%, 55%, and 76% and 0%, 21%, 56%, and 62% for PI-RADS 2, 3, 4, and 5 in the test and control cohorts, respectively (Chi-square P = 0.78). Multivariate logistic regression showed no significant association between the presence of prospectively measured ADC and csPCa (odds ratio 1.1, 95% confidence interval 0.7-1.7, P = 0.82). CONCLUSION: Prospective ADC measurement may not impact PI-RADS category assignments or positivity rates for csPCa under current guidelines. Future versions of PI-RADS may need to incorporate ADC into scoring rules to realize their potential.

The Negative Predictive Value of a PI-RADS Version 2 Score of 1 on Prostate MRI and the Factors Associated With a False-Negative MRI Study.

OBJECTIVE. The purpose of this study was to calculate the negative predictive value of a prostate MRI study with a Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of 1 (hereafter referred to as a PI-RADS 1 MRI study) and to explore the patient characteristics and MRI-based factors associated with an MRI study with false-negative results. MATERIALS AND METHODS. A total of 542 consecutive patients with a PI-RADS 1 MRI study obtained between January 2016 and July 2019 were retrospectively identified. Patient charts were examined to identify those patients who subsequently underwent systematic prostate biopsy within 1 year of undergoing MRI or at any later date if the biopsy was negative. Patient characteristics and MRI-specific factors were recorded. Two blinded radiologists evaluated the quality of the axial T2-weighted, DWI, and apparent diffusion coefficient sequences; measured the volume of the bladder, the prostate gland, and rectal gas; and determined whether the peripheral zone was avidly enhancing and whether low signal intensity was seen in 50% or more of the peripheral zone on T2-weighted images. Interobserver agreement was tested. Univariable and multivariable logistic regression models were built. RESULTS. A total of 150 patients (median age, 63 years; interquartile range, 56-70 years) were included. Of these patients, 19 (13%) had prostate cancer with a Gleason score of 3 + 4 or greater, yielding a negative predictive value of 87%. Both low T2 signal intensity in the peripheral zone and the prostate-specific antigen level were associated with a false-negative PI-RADS 1 assessment (odds ratio, 4.9 [95% CI, 1.6-14.9; p = 0.006] and 1.1 [95% CI, 1.0-1.2; p = 0.03], respectively). A cutoff prostate-specific antigen level of 3.97 ng/mL resulted in sensitivity and specificity of 89% and 21%, respectively. There was moderate interobserver agreement for low T2 signal intensity in the peripheral zone (κ coefficient = 0.75). CONCLUSION. Even among select patients who undergo subsequent biopsy because of a high clinical suspicion of prostate cancer, a PI-RADS 1 prostate MRI study has a high negative predictive value. A T2-hypointense peripheral zone and an elevated prostate-specific antigen level are significantly associated with a false-negative MRI study.

Development of a Nationally Representative Coordinated Registry Network for Prostate Ablation Technologies.

PURPOSE: The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. MATERIALS AND METHODS: A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. RESULTS: The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF-5 (International Index of Erectile Function-5), the I-PSS (International Prostate Symptom Score), the EPIC-26 (Expanded Prostate Cancer Index Composite-26) and the MSHQ-EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. CONCLUSIONS: A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

Contemporary treatment patterns and outcomes of sarcomatoid bladder cancer.

PURPOSE: To characterize the treatment patterns and survival outcomes of sarcomatoid bladder cancer, a rare urothelial variant histology using a large population level cancer database. METHODS: The National Cancer Database was queried for all cases of sarcomatoid bladder cancer using International Classification of Disease-O-3 morphologic code 8122 between 2004 and 2014. Primary outcome was overall survival. RESULTS: A total of 489 patients met our inclusion criteria and were included in our analysis. Average age at diagnosis was 70.4 years. The majority of the population was male (61.8%) and Caucasian (92.2%). Tumor characteristics included 23.7% cT1, 41.1% cT2 and 15.3% cT3 or above. Median overall survival was 18.4 months (95% CI 13.3-23.6). On multivariate Cox proportional analysis, radical cystectomy alone or with multimodal therapy (chemotherapy or radiotherapy) resulted in a statistically significant reduction in the risk of death as compared to bladder preservation surgery alone. Survival in the radical cystectomy group did not differ between radical cystectomy alone and those receiving either neoadjuvant or adjuvant chemotherapy. CONCLUSIONS: Sarcomatoid bladder cancer has poor prognosis with 18.4-month median overall survival. While our data suggest that aggressive treatment improves outcomes, the role of multimodal therapy is unclear. Future study should continue to focus on multi-institutional collaboration to determine the most effective therapy.

Perioperative blood transfusion predicts short term morbidity after nephrectomy.

INTRODUCTION: To assess 30-day morbidity and mortality following partial nephrectomy (PN) and radical nephrectomy (RN) with relation to the administration of perioperative blood transfusions PBT). MATERIALS AND METHODS: The National Surgical Quality Improvement Program was queried for patients with malignant renal tumors (International Classification of Diseases Ninth Revision codes 189-189.2) who underwent RN (Current Procedure Terminology codes 50220, 50225, 50230, 50234, 50236, 50545, 50546, 50548) or PN (50240, 50543) between 2005-2013. Patients were stratified by transfusion status and assessed for postoperative outcomes both separately and in composite, including morbidity, mortality, infectious complications, and pulmonary complications. Univariate and multivariate analyses were performed to identify significant independent predictors of these composite outcomes. RESULTS: The overall transfusion rates were 15.8% and 8.2% for RN and PN, respectively. On multivariate analysis, PBT was associated with increased morbidity (RN: OR 2.147, 95% CI 1.687-2.733; PN: OR 2.081, 95% CI 1.434-3.022), mortality (RN: OR 2.308, 95% CI 1.159-4.598; PN: OR 5.166, 95% CI 1.207-22.12), infectious complications (RN: OR 1.656, 95% CI 1.151-2.383; PN: OR 1.945, 95% CI 1.128-3.354) and pulmonary complications (RN: OR 3.040, 95% CI 2.125-4.349; OR 3.771, 95% CI 2.108-6.746). CONCLUSIONS: For patients undergoing RN or PN there is a significant association between receipt of PBT and 30-day postoperative outcomes, specifically overall morbidity, mortality, infectious complications, and pulmonary complications. The mechanism that underlies these effects has not been elucidated, but it most likely involves immunomodulation and acute lung injury. Future research should focus on formulating comprehensive transfusion guidelines for oncologic-related nephrectomies.

Perioperative blood transfusion in radical cystectomy: Analysis of the National Surgical Quality Improvement Program database.

OBJECTIVES: To determine whether perioperative blood transfusion is associated with worse 30-day postoperative outcomes in radical cystectomy patients. METHODS: Utilizing the National Surgical Quality Improvement Program database, we identified 2934 patients diagnosed with bladder cancer (International Classification of Diseases Ninth Revision codes 188-188.9) who underwent radical cystectomy (Current Procedure Terminology codes 51570, 51575, 51580, 51585, 51590, 51595, 51596) between 2005 and 2013. Patients were stratified by transfusion status and assessed based on four composite postoperative outcomes: morbidity, surgical site infection, mortality and readmission. Multivariate regression models were used to determine significant independent predictors of the composite outcomes. RESULTS: Overall, 40.1% of patients received a transfusion, and there were significant differences in baseline variables such as age, sex, body mass index, smoking history and comorbidities. Transfusion was associated with increased morbidity, surgical site infection, readmission, operative time and length of stay on unadjusted analyses. On multivariate regression, transfusion was associated with increased morbidity (OR 1.361, 95% CI 1.131-1.638) and surgical site infection (OR 1.371, 95% CI 1.070-1.757). CONCLUSIONS: Perioperative blood transfusion is associated with increased risk of postoperative infection and morbidity. Previous work in this area has focused on negative long-term oncological outcomes, but this is the first study to examine short-term postoperative outcomes. Future research should focus on the immunosuppressive mechanism of perioperative blood transfusion and on restrictive transfusion guidelines for oncology patients.

A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.

Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions. Both OncoTarget, which identifies high-affinity inhibitors of individual master regulator (MR) proteins, and OncoTreat, which identifies drugs that invert the transcriptional activity of hyperconnected MR modules, produced highly significant 30-day disease control rates (68% and 91%, respectively). Moreover, of 18 OncoTreat-predicted drugs, 15 induced the predicted MR-module activity inversion in vivo. Predicted drugs significantly outperformed antineoplastic drugs selected as unpredicted controls, suggesting these methods may substantively complement existing precision cancer medicine approaches, as also illustrated by a case study. SIGNIFICANCE: Complementary precision cancer medicine paradigms are needed to broaden the clinical benefit realized through genetic profiling and immunotherapy. In this first-in-class application, we introduce two transcriptome-based tumor-agnostic systems biology tools to predict drug response in vivo. OncoTarget and OncoTreat are scalable for the design of basket and umbrella clinical trials. This article is highlighted in the In This Issue feature, p. 1275.

Can staccato and interrupted/fractionated uroflow patterns alone correctly identify the underlying lower urinary tract condition?

PURPOSE: Worldwide, uroflowmetry without simultaneous electromyography is often the only testing performed during the initial assessment of children with lower urinary tract symptoms. Various alterations in uroflow pattern are thought to indicate particular types of lower urinary tract conditions, specifically staccato uroflow indicating dysfunctional voiding and intermittent/fractionated uroflow indicating detrusor underactivity. We determined how reliable uroflow pattern alone is as a surrogate for simultaneously measured pelvic floor electromyography activity during voiding, and how well staccato and interrupted uroflow actually correlate with the diagnoses they are presumed to represent. MATERIALS AND METHODS: We reviewed uroflow/electromyography studies performed during the initial evaluation of 388 consecutive neurologically and anatomically normal patients with persistent lower urinary tract symptoms. We identified those with staccato, interrupted/fractionated and mixed uroflow based on current International Children's Continence Society guidelines. RESULTS: A total of 69 girls (58.5%) and 49 boys (41.5%) met inclusion criteria. Staccato uroflow was noted in 60 patients, interrupted/fractionated uroflow in 28 and a combination in 30. An active electromyography during voiding confirmed the diagnosis of dysfunctional voiding in 33.3% of patients with staccato, 46.4% with interrupted/fractionated and 50% with mixed uroflow patterns. CONCLUSIONS: Diagnoses based on uroflow pattern appearance without simultaneous electromyography to support them can be misleading, and reliance on uroflow pattern alone can lead to overdiagnoses of dysfunctional voiding and detrusor underactivity. When assessing patients with uroflow, an accompanying simultaneous pelvic floor electromyography is of utmost importance for improving diagnostic accuracy and thereby allowing for the most appropriate therapy.

Association of Patient and Imaging-Related Factors With False Negative MRI-Targeted Prostate Biopsies of Suspicious PI-RADS 4 and 5 Lesions.

OBJECTIVE: To investigate specific imaging and patient-related factors associated with a false negative (FN) MRI-targeted prostate fusion biopsies (TBx) of suspicious MRI lesions. METHODS: Retrospective study of men with PI-RADS 4 or 5 lesions November, 2015-December 2020 with TBx and systematic biopsy (SBx) performed. Only FN and true positive (TP) targeted lesions were included. FN biopsy was defined as a negative TBx with a positive systematic core in the ROI or perilesional sextant. Logistic regression was used to determine the association of patient and imaging-specific factors with the probability of a FN TBx. RESULTS: 361 PI-RADS 4 or 5 lesions in 304 patients, including 67 FN (19%) and 294 TP (81%) were included. There was a significant inverse association between lesion size (OR: 0.94, P-value: .02), presence of a suspicious DRE (OR: 0.36, P-value: .02) and PSA density (OR: 0.01, P-value: .004) on the probability of obtaining a FN TBx. There was no association between age, biopsy indication, use of an enema before MRI, prostate size, or discrepant US and MRI segmentation volumes on the probability of a FN TBx. CONCLUSION: In this cohort, SBx detected 19% of csPCa missed on TBx. Smaller PI-RADS 4/5 lesions, lower PSAD values, and a normal DRE were all associated with an increased probability of a FN TBx.

Dosimetric feasibility of neurovascular bundle-sparing stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer to preserve erectile function.

OBJECTIVE: We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy. METHODS: Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) <60%, V32Gy <70%, V28Gy <90%. RESULTS: Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (p < 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (p < 0.01) and 25% with spacer (p < 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints. CONCLUSIONS: NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation. ADVANCES IN KNOWLEDGE: This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.

Telemedicine in management of genitourinary malignancies: Patient and physician perspectives.

PURPOSE: The rapid expansion of telemedicine has presented a challenge for the care of patients with genitourinary malignancies. We sought to assess patient and physician perspectives on the use of telemedicine for genitourinary cancer care. METHODS: We conducted a prospective cross-sectional study of patients who had telemedicine visits with urology, medical oncology, or radiation oncology for management of genitourinary malignancies from July-August 2020. Patients and physicians each received a questionnaire regarding the telemedicine experience. Responses were scored on a 5-point Likert scale. The primary outcomes of the study were patient and physician satisfaction. RESULTS: Of the 115 patients who enrolled, we received 96 patient responses and 46 physician responses. Overall, 77% of patients and 70% of physicians reported being "extremely satisfied" with the telemedicine encounter. Satisfaction was high among all components of the encounter including patient-physician communication, counseling, shared decision making, time spent, timeliness and efficiency, and convenience. Additionally, 78% of patients and 85% of physicians "strongly agreed" that they were able to discuss sensitive topics about cancer care as well as they could at an in-person visit. Nine telemedicine visits (9%) encountered technological barriers. Technological barriers were associated with lower overall satisfaction scores among both patients and physicians (p ≤ 0.01). CONCLUSION: We observed high levels of patient and physician satisfaction for telemedicine visits for management of genitourinary malignancies. Technological barriers were encountered by 9% of patients and were associated with decreased satisfaction.

NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation.

Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function. SIGNIFICANCE: Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance.See related commentary by Finch and Baena, p. 2132.This article is highlighted in the In This Issue feature, p. 2113.

NF-kappaB regulates androgen receptor expression and prostate cancer growth.

Prostate cancers that progress during androgen-deprivation therapy often overexpress the androgen receptor (AR) and depend on AR signaling for growth. In most cases, increased AR expression occurs without gene amplification and may be due to altered transcriptional regulation. The transcription factor nuclear factor (NF)-kappaB, which is implicated in tumorigenesis, functions as an important downstream substrate of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, AKT, and protein kinase C and plays a role in other cancer-associated signaling pathways. NF-kappaB is an important determinant of prostate cancer clinical biology, and therefore we investigated its role in the regulation of AR expression. We found that NF-kappaB expression in prostate cancer cells significantly increased AR mRNA and protein levels, AR transactivation activity, serum prostate-specific antigen levels, and cell proliferation. NF-kappaB inhibitors decrease AR expression levels, prostate-specific antigen secretion, and proliferation of prostate cancer cells in vitro. Furthermore, inhibitors of NF-kappaB demonstrated anti-tumor activity in androgen deprivation-resistant prostate cancer xenografts. In addition, levels of both NF-kappaB and AR were strongly correlated in human prostate cancer. Our data suggest that NF-kappaB can regulate AR expression in prostate cancer and that NF-kappaB inhibitors may have therapeutic potential.

Evaluation of molecular forms of prostate-specific antigen and human kallikrein 2 in predicting biochemical failure after radical prostatectomy.

Most pretreatment risk-assessment models to predict biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer rely on total prostate-specific antigen (PSA), clinical stage, and biopsy Gleason grade. We investigated whether free PSA (fPSA) and human glandular kallikrein-2 (hK2) would enhance the predictive accuracy of this standard model. Preoperative serum samples and complete clinical data were available for 1,356 patients who underwent RP for localized prostate cancer from 1993 to 2005. A case-control design was used, and conditional logistic regression models were used to evaluate the association between preoperative predictors and BCR after RP. We constructed multivariable models with fPSA and hK2 as additional preoperative predictors to the base model. Predictive accuracy was assessed with the area under the ROC curve (AUC). There were 146 BCR cases; the median follow up for patients without BCR was 3.2 years. Overall, 436 controls were matched to 146 BCR cases. The AUC of the base model was 0.786 in the entire cohort; adding fPSA and hK2 to this model enhanced the AUC to 0.798 (p=0.053), an effect largely driven by fPSA. In the subgroup of men with total PSA

Circulating prostate tumor cells detected by reverse transcription-PCR in men with localized or castration-refractory prostate cancer: concordance with CellSearch assay and association with bone metastases and with survival.

BACKGROUND: Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival. METHODS: KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch; Veridex) approved for clinical use. RESULTS: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (> or =80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%-85%) and correlated (Kendall tau, 0.60-0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status. CONCLUSIONS: Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.

Open radical retropubic prostatectomy gives favourable surgical and functional outcomes after transurethral resection of the prostate.

OBJECTIVES: To assess the peri- and postoperative outcome of patients treated with open radical retropubic prostatectomy (RRP) for prostate cancer and who had previously undergone transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Prospectively collected data from a consecutive series of 1760 patients who had RRP between July 2003 and June 2007 at our institution were used to retrospectively match 62 cases (with previous TURP) with the same number of controls (without previous TURP). Matching variables were patient age, body mass index, prostate volume, preoperative total prostate-specific antigen (PSA) level, Gleason score, pathological stage, and intraoperative nerve-sparing procedure. Complete 1-year follow-up data were available for all patients. All collected data on surgery and perioperative complications were analysed. Functional outcome data at the 1-year follow-up were evaluated by applying an institutional questionnaire. Sexual function was assessed using the abbreviated International Index of Erectile Function-5 questionnaire, and urinary control was evaluated by defining complete urinary control as no pad usage. RESULTS: The rate of complete urinary control rate in cases and controls was similar (81% vs 82%). When nerves were spared, 60% (15/25) of patients in either group were capable of sexual intercourse. The overall positive surgical margin rate was insignificantly higher in cases (19% vs 13, P>0.05). After 1 year of follow-up the biochemical recurrence rate (PSA>0.04 ng/mL) did not differ significantly in patients who had RRP after TURP vs RRP alone (six of 62, 10%, vs five of 62, 8%; P=0.77). CONCLUSIONS: RRP for prostate cancer in patients who have had previous TURP does not result in a higher perioperative complication rate, or a worse functional outcome.

Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes.

BACKGROUND: Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement. METHODS: Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria. RESULTS: Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment. CONCLUSIONS: Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

The Prevalence of Bladder Cancer During Cystoscopy for Asymptomatic Microscopic Hematuria.

OBJECTIVE: To investigate the rate of bladder cancer in patients undergoing cystoscopic evaluation for asymptomatic microscopic hematuria (AMH) in order to identify groups at sufficiently low-risk for bladder cancer in whom invasive testing may be avoided. METHODS: We performed a retrospective review of patients who underwent cystoscopic evaluation for AMH between 2010 and 2018. Age, gender, smoking status, history of pelvic radiation, and number of red blood cells per high-power field on urine microscopy were recorded. We used logistic regression to explore the association between specific risk factors and a diagnosis of bladder cancer on cystoscopy. RESULTS: Among the 2118 patients who underwent cystoscopy for AMH, 25 patients (1.2%) were diagnosed with a bladder cancer, all of which were nonmuscle invasive urothelial carcinoma. There were no bladder cancers detected in patients under the age of 50. Older age and positive smoking history were significantly associated with bladder cancer. CONCLUSION: Bladder cancer was an uncommon finding on cystoscopy among patients being evaluated for AMH, especially in younger patients. We confirmed several known risk factors for bladder cancer, including older age and smoking history. Further studies are required to evaluate the utility of cystoscopy for identifying latent bladder cancers in low-risk patients.

Assessment of Discomfort and Pain in Patients Undergoing Fusion Magnetic Resonance Imaging-guided vs TRUS-guided Prostate Biopsy.

OBJECTIVE: To investigate patient pain perception from receiving magnetic resonance imaging fusion-guided prostate biopsy (FBx) in addition to transrectal ultrasound-guided template biopsy (TBx) vs pain from standard TBx alone. MATERIALS AND METHODS: Patients undergoing FBx + TBx or TBx alone from April 2016 to February 2017 completed a validated pain survey after biopsy. Responses were graded from 0 to 10 (0: no pain or willing to return for repeat procedure; 10: excruciating pain or not willing to return for repeat procedure if necessary). Procedures were performed by a single urologist with a 1% lidocaine periprostatic nerve block. Pain scores between groups were compared via Mann-Whitney U test. RESULTS: A total of 170 patients were included, with 96 FBx + TBx and 74 TBx. For FBX + TBx and TBx, mean age was 68.6 (±9.7) and 66.1 (±8.3) (P = .08), and median number of cores was 14.5 (8-22) and 12 (6-14) (P < .001), respectively. Both groups had mild pain from the procedure overall (median pain score 3 [range 0-9]), the probe insertion (2 [0-8]), and the biopsies themselves (3 [1-10]). If necessary, both groups were very willing to come back for the same procedure again (1 [0-10]). CONCLUSION: Patients reported no difference in pain or discomfort with FBx + TBx relative to TBx alone. Both procedures were mildly painful with patients very willing to return for repeat biopsy if necessary. Patients' pain experience should not influence whether additional FBx is performed.