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.

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.

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.

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.

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.

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.

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.

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.

A novel model to correlate hydrogel spacer placement, perirectal space creation, and rectum dosimetry in prostate stereotactic body radiotherapy.

BACKGROUND: The SpaceOAR hydrogel is employed to limit rectal radiation dose during prostate radiotherapy. We identified a novel parameter - the product of angle θ and hydrogel volume - to quantify hydrogel placement. This parameter predicted rectum dosimetry and acute rectal toxicity in prostate cancer patients treated with stereotactic body radiotherapy to 36.25 Gy in 5 fractions. METHODS: Twenty men with low- and intermediate-risk prostate cancer underwent hydrogel placement from 2015 to 2017. Hydrogel symmetry was assessed on the CT simulation scan in 3 axial slices (midgland, 1 cm above midgland, 1 cm below midgland). Two novel parameters quantifying hydrogel placement - hydrogel volume and angle θ formed by the prostate, hydrogel, and rectum - were measured, and the normalized product of θ and hydrogel volume calculated. These were then correlated with perirectal distance, rectum maximum 1-3 cc point doses (rDmax 1-3 cc), and rectum volumes receiving 80-95% of the prescription dose (rV80-95%). Acute rectal toxicity was recorded per RTOG criteria. RESULTS: In 50% of patients, hydrogel placement was symmetric bilaterally to within 1 cm of midline in all three CT simulation scan axial slices. Lateral hydrogel asymmetry < 2 cm in any one axial slice did not affect rectum dosimetry, but absence of hydrogel in the inferior axial slice resulted in a mean increase of 171 cGy in the rDmax 1 cc (p < 0.005). The perirectal distance measured at prostate midgland, midline (mean 9.1 ± 4.3 mm) correlated strongly with rV95 (R2 0.6, p < 0.001). The mean hydrogel volume and θ were 10.3 ± 4.5 cc and 70 ± 49°, respectively. Perirectal distance, rV95 and rDmax 1 cc correlated with hydrogel angle θ (p < 0.01), and yet more strongly with the novel metric θ*hydrogel volume (p < 0.001). With a median follow up of 14 months, no rectal toxicity >grade 2 was observed. Low grade rectal toxicity was observed in a third of men and resolved within 1 month of SBRT. Men who had these symptoms had higher rDmax 1 cc and smaller θ*hydrogel volume measurements. CONCLUSIONS: Optimal hydrogel placement occurs at prostate midgland, midline. The novel parameter θ*hydrogel volume describes a large proportion of rectum dosimetric benefit derived from hydrogel placement, and can be used to assess the learning curve phenomenon for hydrogel placement.

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.

Impact of a Structured Reporting Template on Adherence to Prostate Imaging Reporting and Data System Version 2 and on the Diagnostic Performance of Prostate MRI for Clinically Significant Prostate Cancer.

PURPOSE: The aim of this study was to assess the impact of a structured reporting template on adherence to the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon and on the diagnostic performance of prostate MRI to detect clinically significant prostate cancer (CS-PCa). METHODS: An imaging database was searched for consecutive patients who underwent prostate MRI followed by MRI-ultrasound fusion biopsy from October 2015 through October 2017. The initial MRI reporting template used included only subheadings. In July 2016, the template was changed to a standardized PI-RADS-compliant structured template incorporating dropdown menus. Lesion, patient characteristics, pathology, and adherence to the PI-RADS lexicon were extracted from MRI reports and patient charts. Diagnostic performance of prostate MRI to detect CS-PCa using combined ultrasound-MRI fusion and systematic biopsy as a reference standard was assessed. RESULTS: Three hundred twenty-four lesions in 202 patients (average age, 67 years; average prostate-specific antigen level, 5.9 ng/mL) were analyzed, including 217 MRI peripheral zone (PZ) lesions, 84 MRI non-PZ lesions, and 23 additional PZ lesions found on systematic biopsy but missed on MRI. Thirty-three percent (106 of 324) were CS-PCa. Adherence to the PI-RADS lexicon improved from 32.9% (50 of 152) to 88.4% (152 of 172) (P < .0001) after introduction of the structured template. The sensitivity of prostate MRI for CS-PCa in the PZ increased from 53% to 70% (P = .011). There was no significant change in specificity (60% versus 55%, P = .458). CONCLUSIONS: A structured template with dropdown menus incorporating the PI-RADS lexicon and classification rules improves adherence to PI-RADS and may increase the diagnostic performance of prostate MRI for CS-PCa.

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.

Oncologic Outcomes of Definitive Treatments for Low- and Intermediate-Risk Prostate Cancer After a Period of Active Surveillance.

BACKGROUND: To compare oncologic outcomes of different definitive treatment (DT) modalities in a cohort of patients with prostate cancer (PCa) after active surveillance (AS). METHODS: We identified 237 patients with National Comprehensive Cancer Network (NCCN) low- and intermediate-risk prostate cancer diagnosed from 1990 to 2012 who did not undergo immediate DT within 12 months of diagnosis (ie, AS patients as well as watchful waiting and those refusing DT). Charts were examined for clinical/pathologic data and type of DT: surgery (RP), radiation including brachytherapy (XRT), cryotherapy, and androgen deprivation therapy monotherapy (ADT). The impact of DT on oncologic outcomes of biochemical recurrence (BCR), metastasis, disease-specific (DSS), and overall survival (OS) was examined with the Cox proportional hazards model, along with the Kaplan-Meier method and log-rank test. RESULTS: After median time on AS of 63.4 months, 40% of patients underwent DT: 47% XRT, 28% RP, 14% ADT, and 11% cryotherapy. On multivariable analysis, the use of XRT predicted higher BCR (hazard ratio [HR] 6.1, P = .001) and worse overall mortality (HR 2.1, P = .03) compared with other treatments, controlling for age, Charlson Comorbidity Index (CCI), stage, Gleason score, and NCCN risk category. Median follow-up was 71.7 months. On Kaplan-Meier analysis, 10-year OS was superior for RP versus XRT among patients with prostatic specific antigen (PSA) velocity >2.0 ng/mL/y. CONCLUSIONS: Low- and intermediate-risk patients with PCa who progress to DT after AS may be inadequately treated with radiation therapy compared with other DT modalities, especially when pretreatment PSA velocity is > 2 ng/mL/y.

Timing and Predictors of Early Urologic and Infectious Complications After Renal Transplant: An Analysis of a New York Statewide Database.

OBJECTIVES: The most common complications after renal transplant are urologic and are a cause of significant morbidity in a vulnerable population. We sought to characterize the timing and predictors of urologic complications after renal transplant using a statewide database. MATERIALS AND METHODS: We queried the New York Statewide Planning and Research Cooperative System database to identify patients who underwent renal transplant from 2005 to 2013. Postoperative complications included hydronephrosis, ureteral stricture, vesicoureteral reflux, nephrolithiasis, and urinary tract infections. Cox proportional hazards model was used to assess independent predictors of urologic complications. RESULTS: In total, 9038 patients were included in the analyses. Urologic complications occurred in 11.3% of patients and included hydronephrosis (12.0%), nephrolithiasis (2.8%), ureteral stricture (2.4%), and vesicoureteral reflux (1.5%). We found that 23% experienced at least one urinary tract infection. On multivariate analysis, predictors of urologic complications included medicare insurance, hypertension, and prior urinary tract infection. Graft recipients from living donors were less likely to experience urologic complications than deceased-donor kidney recipients (P < .001). CONCLUSIONS: Urologic complications occur in a significant proportion of renal transplants. Further study is needed to identify risk factors for complications after renal transplantation to decrease morbidity in this vulnerable population.

Collecting duct carcinoma of the kidney: Disease characteristics and treatment outcomes from the National Cancer Database.

OBJECTIVE: To use a large population-level database to assess survival outcomes for collecting duct renal cell carcinoma (CDRCC). MATERIALS AND METHODS: The National Cancer Database was queried for all cases of CDRCC and clear cell renal cell carcinoma (CCRCC) from 2004 to 2013. After removing patients with other cancer diagnoses, the analytic cohort was composed of 201,686 CCRCC and 577 CDRCC cases. Kaplan-Meier and cox proportional hazards analysis were employed to model survival. RESULTS: Compared to CCRCC, patients with CDRCC presented with higher grade and stage, node positive, and metastatic disease (70.7% vs. 30.0% with metastasis; P<0.001). Overall median survival for CDRCC was 13.2 months (95% CI: 11.0-15.5) compared to the 122.5 months (95% CI: 121.0-123.9) for CCRCC. On multivariate analysis of the CDRCC cohort, increasing T stage, high-grade disease, and metastasis were predictors of mortality. Of 184 patients with metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) whereas the rest were treated with chemo/radiation or observed. Survival outcomes were improved in patients who received both CNx with chemo/radiation compared to CNx alone (hazard ratio = 0.51, 95% CI: 0.32-0.79) or chemo/radiation alone (hazard ratio = 0.57, 95% CI: 0.37-0.89) on multivariate analysis. CONCLUSION: CDRCC is an aggressive subtype of renal cell carcinoma. Median survival is 13 months after diagnosis, drastically lower than for CCRCC. More than 70% of patients have metastatic disease at diagnosis. Chemo/radiation in addition to CNx is associated with a survival benefit over single mode therapy.

Predictors of biochemical recurrence after primary focal cryosurgery (hemiablation) for localized prostate cancer: A multi-institutional analytic comparison of Phoenix and Stuttgart criteria.

BACKGROUND: The Phoenix definition (PD) and Stuttgart definition (SD) designed to determine biochemical recurrence (BCR) in patients with postradiotherapy and high-intensity focused ultrasound organ-confined prostate cancer are being applied to follow patients after cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria in patients who underwent primary focal cryosurgery (PFC). MATERIALS AND METHODS: We performed a retrospective review of patients who underwent PFC (hemiablation) at 2 referral centers from 2000 to 2014. Patients were followed up with serial prostate-specific antigen (PSA). PSA levels, pre- and post-PFC biopsy, Gleason scores, number of positive cores, and BCR (PD = [PSA nadir+2ng/ml]; SD = [PSA nadir+1.2ng/ml]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox regression and survival analyses were performed to assess time to BCR using PD and SD. RESULTS: A total of 163 patients were included with a median follow-up of 36.6 (interquartile range: 18.9-56.4) months. In all, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariable Cox regression, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (hazard ratio [HR] = 1.4, P = 0.001) and SD (HR = 1.3, P = 0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR = 2.2, P = 0.024) but not SD (HR = 1.4, P = 0.181). Survival analysis demonstrated a 3-year BCR-free survival rate of 56% and 36% for PD and SD, respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have residual/recurrent cancer. Of those with prostate cancer on post-PFC biopsy, 57.1% of those with BCR by the PD and 66.7% of those with BCR by the SD were found to have a Gleason score ≥7. CONCLUSION: Both the PD and the SD may be used to determine BCR in post-PFC patients. However, the ideal definition of BCR after PFC remains to be elucidated.

Outcomes and Prognostic Factors of Primary Urethral Cancer.

OBJECTIVE: To identify prognostic and treatment factors for primary urethral cancer using a nationwide database. MATERIALS AND METHODS: The National Cancer Database was queried for all cases of primary urethral cancer from 2004 to 2013. Patients with other cancer diagnoses, metastasis, or diagnosis on autopsy were excluded. Proportional hazards regression was used to identify independent predictors of overall survival in patients with primary urethral cancer. Because we hypothesized that predictors may covary by sex, we also performed regression analysis stratified by sex. RESULTS: We identified 1268 men and 869 women with primary urethral cancer. Women tended to have more advanced tumors and adenocarcinoma histology. Median survival for the entire cohort was 49 months (43-55), with 5- and 10-year survival rates of 46% and 31%, respectively. On multivariate analysis, age, race, stage, grade, and Charlson comorbidity index were independent predictors of overall survival. Histology was not a predictor of overall survival in the combined model; however, adenocarcinoma in women increased hazards of death, whereas it decreased hazards of death in men when compared with squamous cell carcinoma. CONCLUSION: Men and women with primary urethral cancer had significant differences in histology, grade, and nodal status. In addition to several expected disease-related factors, black race was associated with increased mortality for patients with primary urethral cancer.

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.