Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial.

PURPOSE: Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer. PATIENTS AND METHODS: This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile. RESULTS: The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0-68.0] and 21.9 ng/mL (IQR, 14.6-42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078). CONCLUSIONS: Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.

Age related differences in primary testicular lymphoma: A population based cohort study.

INTRODUCTION: Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. METHODS: The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. RESULTS: There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1-50), and 72 (IQR 51-95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57-0.71) and 0.34 (95% CI: 0.31-0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25-6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26-0.40) compared to HR of 0.40 (95% CI: 0.37-0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05- 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. CONCLUSIONS: PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.

Salvage partial gland ablation for recurrent prostate cancer following primary partial gland ablation: Functional and oncological outcomes.

INTRODUCTION AND OBJECTIVE: Partial gland ablation (PGA) for localised prostate cancer (CaP) aims to eradicate clinically significant tumours while preserving healthy tissue, thereby decreasing the likelihood of side effects compared to whole-gland approaches. Although salvage radical prostatectomy (sRP) is a well-described salvage option in cases of PGA failure, the evidence supporting salvage PGA (sPGA) is limited. We hereby report the oncologic and functional outcomes of patients treated with sPGA following initial treatment with primary PGA (pPGA). METHODS: We describe the findings of a retrospective review of patients who had a CaP recurrence after pPGA and then underwent sPGA, at 3 medical centers in Ontario, Canada, between 2005 and 2017. Oncological outcomes following sPGA were assessed for biochemical recurrence (BCR) and biopsy-proven recurrence (BPR). Functional outcomes were described using the international prostate symptom score (IPSS), international index of erectile function (IIEF), and rates of urinary incontinence (use of >1 pad/day). RESULTS: We identified 25 patients who underwent sPGA following pPGA (hemiablation in 48% and zonal ablation in 52% of the patients). The median length of time was 16.8 months (interquartile range [IQR] 14.0-19.1) from pPGA to sPGA and 47.06 months (IQR 19.9-171.3) from pPGA to date of last follow up. High intensity focused ultrasound (HIFU) was the only modality used in all patients. At baseline, the median age was 65 years (IQR 52-77) and median prostate specific antigen (PSA) level was 7.46 ng/mL (IQR 1-25). The median time from pPGA to BPR was 12.7 months (IQR 5.19-36). At BPR following pPGA, 4 patients (17%) had CaP grade group (GG) 1, 10 patients (42%) had GG2, 6 patients (25%) had GG3, and 4 patients (17%) had GG4 disease, with a median PSA of 3.58 ng/mL (IQR 0.67-19). The median length of follow up after sPGA was 27.3 months (IQR 14.5-86.3). Following sPGA, 13/25 patients (52%) had BCR with median time to recurrence of 14 months (IQR 2.5-82.15), with a recurrence-free survival of 24.5 months (95% confidence interval: 15.3-not reached). Of those 13 patients, 4 were managed with sRP, 4 were managed with salvage radiotherapy, 3 were managed with androgen-deprivation therapy, 1 had a third PGA with HIFU, and 1 was managed with active surveillance. The mean change from baseline to last follow up in IPSS and IIEF scores was +1.3 (P = 0.66) and -2.3 (P = 0.32), respectively. Urinary incontinence was reported by 9% of patients at baseline, with only one additional patient developing incontinence following sPGA. CONCLUSION: Our present study demonstrates that after a median follow-up of 27 months, sPGA for recurrent CaP following pPGA provides disease control in up to 50% of patients with nonsignificant detrimental effects on functional outcomes. Appropriate patient selection and adequate staging are important to consider before offering PGA to patients.

Benefit of a more extended pelvic lymph node dissection among patients undergoing radical prostatectomy for localized prostate cancer: A causal mediation analysis.

BACKGROUND: The therapeutic role of extended (ePLND) versus nonextended pelvic lymph node dissection (nePLND) to remove occult micrometastases in men undergoing radical prostatectomy for localized prostate cancer (PC) is conflicting. Therefore, our aim was to quantify the direct effect of ePLND versus nePLND (removal of occult micrometastases), which is not mediated through the detection of nodal disease and potential adjuvant therapy (indirect effect). METHODS: Retrospective, bi-center cohort study of consecutive patients undergoing radical prostatectomy and PLND for PC (January 2006 and December 2016). Patients were followed until April 2018 for the occurrence of either biochemical recurrence or secondary therapy (composite outcome). ePLND was compared to nePLND by unweighted and weighted survival analysis (total effect) as well as by causal mediation analysis (direct and indirect effect). RESULTS: Positive nodal disease was detected in 71 (7%) out of 1008 patients undergoing radical prostatectomy and PLND for PC (ePLND: 368 [36.5%]; nePLND: 640 [63.5%]). Survival analysis demonstrated results in favor of ePLND (unweighted hazard ratio: 0.77 [95% confidence interval: 0.59-1.01], p = .056; weighted hazard ratio: 0.75 [0.56-0.99], p = .044). The causal mediation analysis confirmed the total effect of 0.77 (0.71-0.82). After disentangling this total effect into an indirect effect (via detection of nodal disease and potential adjuvant therapy) and a direct effect (via removal of occult micrometastases), we identified an even more protective direct effect of 0.69 (0.63-0.75). CONCLUSIONS: Our results not only indicate the utility of ePLND but also that its impact is not restricted to a staging benefit and probably involves a therapeutic benefit mediated through the removal of occult micrometastases.

Defining oligometastatic hormone sensitive prostate cancer and clinically significant outcomes: Implications on clinical trials?

PURPOSE: With the current movement toward treating oligometastatic hormone sensitive prostate cancer (OMPC), we design a study with the objective of gathering opinions regarding what would be considered a clinically significant benefit from such treatments. METHODS: Data was collected from physicians of the Society of Urologic Oncology using a self-administered questionnaire using SurveyMonkey. The questionnaire was designed to obtain characteristics on clinical practice of the respondents, definitions used for OMPC and also what would be considered a clinically significant benefit according to the respondents. We present a descriptive analysis of the responses obtained. RESULTS: We obtained 119 responses (response rate of 12.6%) after sending the questionnaire twice with one month apart. Most of them being staff/faculty (89%) practicing in the United States of America (84.87%). Most of the responders referred that a significant proportion of their practice comes from PC patients. Most defined OMPC <3 bone/lymph node metastasis seen with conventional imaging, only 26.9% of the responders used positron emission tomography. Regarding the clinical benefit of metastasis-oriented treatment, a curing rate >10% or an increase in 1 year of androgen deprivation therapy-free survival would make the treatment worthwhile. We present examples of sample size calculations for future clinical trials using these parameters as an expected "clinically-significant" benefit. CONCLUSION: This study shows that most clinicians still support the use of conventional imaging to define OMPC. Our findings show that a curing rate of a minimum of 11% and an androgen deprivation therapy-free survival at 1 year are considered clinically significant and this should be used for estimating the sample size in future clinical trials.

Predictors of prostate-specific antigen testing in men aged ≥55 years: A cross-sectional study based on patient-reported outcomes.

OBJECTIVES: To examine the predictors of prostate-specific antigen discussion with a physician and prostate-specific antigen testing in men aged ≥55 years. METHODS: Utilizing the USA Health Information National Trends Survey, 4th Ed., a cross-sectional study from 2011 to 2014 was carried out to analyze the factors predicting prostate-specific antigen testing and discussion in men ≥55 years. Associations between each covariate and prostate-specific antigen discussion/testing were determined. Multivariable logistic regression models were used to determine clinically relevant predictors of prostate-specific antigen discussion/testing. Due to multiple comparisons, the Bonferroni correction was used. RESULTS: A total of 2731 men included in the Health Information National Trends Survey were analyzed. Several socioeconomic parameters were found to increase the likelihood of men aged ≥55 years to undergo prostate-specific antigen testing: living with a spouse, a higher level of education (college graduate or above), a higher income (>$50 000 annually) and previous history of any cancer. In contrast, current smokers were less likely to undergo prostate-specific antigen testing. Having a prostate-specific antigen discussion with a physician was more likely for men surveyed in 2014, for men who were living with a spouse, who had a higher annual income (>$50 000 annually) and those with a history of any cancer. CONCLUSIONS: Significant inequalities in prostate-specific antigen testing and discussion exist among men in the USA, mainly driven by socioeconomic factors. Ideally, prostate-specific antigen testing and discussion should be based on relevant clinical factors with a shared decision-making approach for every man. Therefore, a better understanding of the socioeconomic factors influencing prostate-specific antigen testing/discussions can inform strategies to reduce existing gaps in care.

Utility of digital rectal examination in a population with prostate cancer treated with active surveillance.

INTRODUCTION: Digital rectal examination (DRE) is part of the clinical evaluation of men on active surveillance (AS). The purpose of the present study is to analyze the value of DRE as a predictor of upgrading in a population of men with prostate cancer (PCa) treated with AS. METHODS: We used the prostate biopsy (PBx) database from an academic center, including PBx from 2006-2018, and identified 2029 confirmatory biopsies (CxPBx) of men treated with AS, of which 726 men had both diagnostic (initial) and CxPBx information available. We did a descriptive analysis and evaluated sensitivity, specificity, and predictive values of DRE for the detection of clinically significant PCa (csPCa). Multivariable regression analysis was done to identify predictors of csPCa. The primary outcome was to evaluate DRE as a predictor of the presence of csPCa at CxPBx. RESULTS: Among the 2029 patients with a CxPBx, 75% had PCa, and of these, 30.3% had upgrading to International Society of Urologic Pathologists (ISUP) grade ≥2. Thirteen percent of men had a suspicious DRE (done by their treating physician). Sensitivity, specificity, negative and positive predictive values of DRE to detect csPCa were best with a prostate-specific antigen (PSA) <4 ng/ml (27%, 88%, 31%, and 87%, respectively). A suspicious DRE at CxPBx, particularly if the DRE at diagnosis was negative, was a predictor of csPCa (odds ratio [OR] 2.34, p=0.038). The main limitation of our study is the retrospective design and the lack of magnetic resonance imaging. CONCLUSIONS: We believe DRE should still be used as part of AS and can predict the presence of csPCa, even with low PSA values. A suspicious nodule on DRE represents a higher risk of upgrading and should prompt further assessment.

Required efficacy for novel therapies in BCG-unresponsive non-muscle invasive bladder cancer: Do current recommendations really reflect clinically meaningful outcomes?

BACKGROUND: Single-arm trials are currently an accepted study design to investigate the efficacy of novel therapies (NT) in non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guérin (BCG) immunotherapy as randomized controlled trials are either unfeasible (comparator: early radical cystectomy; ERC), or unethical (comparator: placebo). To guide the design of such single-arm trials, expert groups published recommendations for clinically meaningful outcomes. The aim of this study was to quantitatively verify the appropriateness of these recommendations. METHODS: We used a discrete event simulation framework in combination with a supercomputer to find the required efficacy at which a NT can compete with ERC when it comes to quality-adjusted life expectancy (QALE). In total, 24 different efficacy thresholds (including the recommendations) were investigated. RESULTS: After ascertaining face validity with content experts, repeated verification, external validation, and calibration we considered our model valid. Both recommendations rarely showed an incremental benefit of the NT over ERC. In the most optimistic scenario, an increase in the IBCG recommendation by 10% and an increase in the FDA/AUA recommendation by 5% would yield results at which a NT could compete with ERC from a QALE perspective. CONCLUSIONS: This simulation study demonstrated that the current recommendations regarding clinically meaningful outcomes for single-arm trials evaluating the efficacy of NT in BCG-unresponsive NMIBC may be too low. Based on our quantitative approach, we propose increasing these thresholds to at least 45%-55% at 6 months and 35% at 18-24 months (complete response rates/recurrence-free survival) to promote the development of clinically truly meaningful NT.

A High Percent Free Prostate Specific Antigen in the Setting of Biochemical Recurrence after Radical Prostatectomy is Associated with Poorer Outcomes: A Validation Study Using Prospectively Collected Biobank Specimens.

PURPOSE: The role of percent free prostate specific antigen (%fPSA) in patients who have undergone radical prostatectomy and subsequently experienced disease relapse is unclear. We previously conducted 2 retrospective studies and found %fPSA 15 or greater in the setting of biochemical recurrence confers more aggressive disease. To validate that finding we used biobank specimens collected prospectively when patients were first diagnosed with biochemical recurrence. MATERIALS AND METHODS: Biobank specimens of patients with undetectable prostate specific antigen after radical prostatectomy and subsequent biochemical recurrence (prostate specific antigen 0.1 ng/ml or greater) were analyzed for %fPSA. Patients were stratified according to the %fPSA cutoff of 15. Univariable and multivariable logistic regression analysis was performed to predict covariates associated with a higher %fPSA. Cox proportional hazard models were performed to evaluate the prognostic effect of %fPSA on androgen deprivation therapy-free survival, metastasis-free survival, castration resistant-free survival and cancer specific survival. RESULTS: A total of 154 men were included in the study, of whom 126 (82%) had %fPSA less than 15 and 28 (18%) had %fPSA 15 or greater. Median followup for %fPSA less than 15 and %fPSA 15 or greater was 75 and 69 months, respectively. Patients with %fPSA 15 or greater had increased hazard of receiving androgen deprivation therapy (43% vs 25%, adjusted HR 2.40, 95% CI 1.12-5.11), metastatic disease (21% vs 7.9%, adjusted HR 4.10, 95% CI 1.11-15.2) and castration resistant prostate cancer (14% vs 4.0%, unadjusted HR 4.14, 95% CI 1.11-15.5) vs %fPSA less than 15, respectively. CONCLUSIONS: Patients with %fPSA 15 or greater were started on androgen deprivation therapy earlier, and they had progression to castration resistant prostate cancer and metastatic stage earlier. %fPSA 15 or greater in the setting of biochemical recurrence after radical prostatectomy is an indicator of a more aggressive disease. Unlike in the diagnostic setting, a higher %fPSA portends a worse clinical outcome.

Salvage radical prostatectomy following focal therapy: functional and oncological outcomes.

OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

Photoselective vaporization of the prostate: study outcomes as a function of risk of bias, conflicts of interest, and industrial sponsorship.

PURPOSE: To investigate the outcomes of comparative studies on photoselective vaporization of the prostate (PVP) as a function of risk of bias (RoB), conflicts of interest (COI), and industrial sponsorship (IS). METHODS: We performed a systematic literature search for comparative studies on PVP [randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs)]. Study selection as well as comprehensive assessment of RoB, COIs, and IS were performed in duplicate. The identified studies were further rated by two independent board-certified urologists as either PVP-favourable or PVP-unfavourable. Descriptive statistics were performed among all identified studies and among the subgroups of studies rated as favourable and unfavourable, respectively. RESULTS: Sixty-five studies qualified for inclusion (25 RTCs and 40 NRCSs) of which 56 (86%) were rated favourable and 9 (14%) unfavourable. A majority of all studies mentioned the absence/presence of potential COIs (78%). In contrast, a sponsorship statement was only found in 29% of the investigations. Studies rated favourable demonstrated a higher percentage of COIs (39% versus 22%). IS was exclusively found among favourable studies. Furthermore, a serious or critical RoB was more often found in favourably rated NRCSs. CONCLUSIONS: COIs and IS seem to be associated with favourable study outcomes in comparative studies on PVP. The transparency of the whole research process from study conception to the dissemination of the results has to be further improved to prevent a harmful effect of COIs and IS on the internal validity of studies.

Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a "Negative Core" in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis.

OBJECTIVE: To assess the impact of excluding Gleason Grade Group 1 (GG1) prostate cancer (CaP) cores from current pre-radical prostatectomy (RP) nomograms. METHODS: Multi-institutional retrospective chart review was performed on all RP patients with prostate biopsy between 2008 and 2018. Patients were individually assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti nomograms using the following iterations: (1) Original [ORIG] - all available core data and (2) Selective [SEL] - GG1 cores considered negative. Nomogram outcomes - lymph node invasion (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations and stratified based on biopsy GG. Clinically significant impact on management (CSIM) was defined as change in LNI risk above or below 2% or 5% (Δ2/Δ5). Nomogram outcomes were validated with RP pathology. RESULTS: 7718 men met inclusion criteria. In men with GG2 who also had GG1 cores, SEL better predicted LNI (MSKCC - ORIG 4.97% vs SEL 3.50%; Briganti - ORIG 4.81% vs SEL 2.49%, RP outcome 2.46%), OCD (MSKCC - ORIG 40.91% vs SEL 48.44%, RP outcome: 68.46%) and ECE (MSKCC - ORIG 57.87% vs SEL 50.38%, RP outcome: 30.41%), but not SVI (MSKCC - ORIG 5.42% vs SEL 3.34%, RP outcome: 5.62%). This was also consistent in patients with GG3-5 disease. The greatest CSIM was on GG1-2 CaP; Δ2 and Δ5 in GG1 patients was 26.3%-31.0% and 1.5%-5.2%, respectively, and Δ2 and Δ5 in GG2 patients was 3.4%-22.2% and 12.3%-13.6%, respectively. CONCLUSION: Excluding GG1 CaP cores from pre-RP nomograms better predicts final RP pathologic outcomes. More importantly, this may better reflect extent of true cancer burden.

Incorporating mpMRI biopsy data into established pre-RP nomograms: potential impact of an increasingly common clinical scenario.

BACKGROUND: We examine the practical application of multiparametric MRI (mpMRI) prostate biopsy data using established pre-RP nomograms and its potential implications on RP intraoperative decision-making. We hypothesize that current nomograms are suboptimal in predicting outcomes with mpMRI targeted biopsy (TBx) data. MATERIALS AND METHODS: Patients who underwent mpMRI-based TBx prior to RP were assessed using the MSKCC and Briganti nomograms with the following iterations: (1) Targeted (T) (targeted only), (2) Targeted and Systematic (TS) and (3) Targeted Augmented (TA) (targeted core data; assumed negative systematic cores for 12 total cores). Nomogram outcomes, lymph node involvement (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations. Clinically significant impact on management was defined as a change in LNI risk above or below 2% (Δ2) or 5% (Δ5). RESULTS: A total of 217 men met inclusion criteria. Overall, the TA iteration had more conservative nomogram outcomes than the T. Moreover, TA better predicted RP pathology for all four outcomes when compared with the T. In the entire cohort, Δ2 and Δ5 were 16.6-25.8% and 20.3-39.2%, respectively. In the subset of 190 patients with targeted and systematic cores, TA was a better approximation of TS outcomes than T in 71% (MSKCC) and 82% (Briganti) of patients. CONCLUSION: In established pre-RP nomograms, mpMRI-based TBx often yield variable and discordant results when compared with systematic biopsies. Future nomograms must better incorporate mpMRI TBx core data. In the interim, augmenting TBx data may serve to bridge the gap.

Active surveillance in intermediate risk prostate cancer.

OBJECTIVES: Active Surveillance (AS) has become an established treatment option for men with low-risk prostate cancer (PCa), demonstrating superior functional outcomes and excellent oncologic outcomes.As such, it has been appealing to extend AS to patients with intermediate risk PCa. We provide a review of the current experience with AS in the intermediate-risk PCa population. METHODS: Risk stratification is the key to treatment success. Many clinical factors (age, percent Gleason 4, PSA density, race/ethnicity, and genetic predisposition) and genomic markers have proven prognostic value in the AS population. We performed a systematic review of the currently available data (randomized trials and prospective cohort studies) to establish the status of AS in the intermediate risk patient population. RESULTS: Our ability to predict the natural history of intermediate risk prostate cancer is imperfect. While the benefits of AS make it an appealing option for men with intermediate risk disease, the published experience todate demonstrates that AS for all men with intermediate risk disease leads to higher rates of metastatic disease and loss of the opportunity for cure. These same studiesalso demonstrate that a subset of patients with intermediate risk disease have indolent disease that may benefit from AS. This heterogeneity is not adequately captured with traditional histopathologic staging. Clinical, genomic, and radiologic biomarkers play a key role in appropriate risk stratification and patient selection. The optimal use of these biomarkers in the intermediate riskpatient is currently the subject of intense evaluation. CONCLUSION: Active surveillance for men at the favorable end of intermediate risk prostate cancer is an appealing alternative to radical therapy, but carries a modest but increased risk of metastatic disease compared to low risk cancer. Many biomarkers are currently being evaluated to enhance precise risk stratification of this important subgroup of patients.

OBJETIVOS: La Vigilancia Activa (VA) es un tratamiento bien establecido para pacientes con cáncer de próstata (CaP) de bajo riesgo, con mejores resultados funcionales y excelentes resultados oncológicos. Como tal, suena atractiva su aplicación en pacientes con CaP de riesgo intermedio. A seguir, presentamosuna revisión de la experiencia actual con el uso de VA en CaP de riesgo intermedio.MÉTODOS: Lo primero es una buena estratificación de riesgo. Hay múltiples factores (edad, porcentaje de Gleason 4, densidad de APE, raza/etnicidad y predisposición genética) y marcadores genéticos que han demostrado ser útiles en la población en VA. Después de hacer una revisión de estos factores en pacientes de riesgo intermedio, hicimos una revisión de la evidenciaactual (estudios aleatorizados y cohortes prospectivas) para dar una visión del uso de VA en esta población. RESULTADOS: Nuestra capacidad para predecir la evolución de pacientes de riesgo intermedio no es perfecta. Si bien los beneficios de VA son atractivos, las experiencia colectiva ha demostrado repetidamente que el uso de VA en pacientes de riesgo intermedio tiene mayor tasa de enfermedad metastásica y pérdida de la oportunidad curativa. Por el otro lado, estos mismos estudios han demostrado que existe un subgrupo de esos pacientes que cursan con enfermedad indolente y se podrían beneficiar de VA. Desafortunadamente, estaheterogeneidad no se define bien con las clasificaciones histopatológicas tradicionales. Los biomarcadores (clínicos, genómicos y radiológicos) serán la clave para una apropiada estratificación de riesgo y selección de pacientes. El uso adecuado de estos biomarcadores en pacientes de riesgo intermedio es actualmente tema de grandes estudios. CONCLUSIONES: La VA es una alternativa de tratamiento atractiva para hombres en el extremo favorable del riesgo intermedio, pero conlleva un riesgo moderadopero real de enfermedad metastásica en comparación con pacientes de riesgo bajo. Múltiples marcadores están siendo evaluados para lograr una predicciónmás precisa del subgrupo de pacientes adecuado.

Vigilancia activa en cáncer de próstata de riesgo intermedio / No disponible

Objetivos: La Vigilancia Activa (VA) es un tratamiento bien establecido para pacientes con cáncer de próstata (CaP) de bajo riesgo, con mejores resultados funcionales y excelentes resultados oncológicos. Como tal, suena atractiva su aplicación en pacientes con CaP de riesgo intermedio. A seguir, presentamos una revisión de la experiencia actual con el uso de VA en CaP de riesgo intermedio. Métodos: Lo primero es una buena estratificación de riesgo. Hay múltiples factores (edad, porcentaje de Gleason 4, densidad de APE, raza/etnicidad y predisposición genética) y marcadores genéticos que han demostrado ser útiles en la población en VA. Después de hacer una revisión de estos factores en pacientes de riesgo intermedio, hicimos una revisión de la evidencia actual (estudios aleatorizados y cohortes prospectivas) para dar una visión del uso de VA en esta población. Resultados: Nuestra capacidad para predecir la evolución de pacientes de riesgo intermedio no es perfecta. Si bien los beneficios de VA son atractivos, las experiencia colectiva ha demostrado repetidamente que el uso de VA en pacientes de riesgo intermedio tiene mayor tasa de enfermedad metastásica y pérdida de la oportunidad curativa. Por el otro lado, estos mismos estudios han demostrado que existe un subgrupo de esos pacientes que cursan con enfermedad indolente y se podrían beneficiar de VA. Desafortunadamente, esta heterogeneidad no se define bien con las clasificaciones histopatológicas tradicionales. Los biomarcadores (clínicos, genómicos y radiológicos) serán la clave para una apropiada estratificación de riesgo y selección de pacientes. El uso adecuado de estos biomarcadores en pacientes de riesgo intermedio es actualmente tema de grandes estudios. Conclusiones: La VA es una alternativa de tratamiento atractiva para hombres en el extremo favorable del riesgo intermedio, pero conlleva un riesgo moderado pero real de enfermedad metastásica en comparación con pacientes de riesgo bajo. Múltiples marcadores están siendo evaluados para lograr una predicción más precisa del subgrupo de pacientes adecuado

Objectives: Active Surveillance (AS) has become an established treatment option for men with low-risk prostate cancer (PCa), demonstrating superior functional outcomes and excellent oncologic outcomes. As such, it has been appealing to extend AS to patients with intermediate risk PCa. We provide a review of the current experience with AS in the intermediate-risk PCa population. Methods: Risk stratification is the key to treatment success. Many clinical factors (age, percent Gleason 4, PSA density, race/ethnicity, and genetic predisposition) and genomic markers have proven prognostic value in the AS population. We performed a systematic review of the currently available data (randomized trials and prospective cohort studies) to establish the status of AS in the intermediate risk patient population. Results: Our ability to predict the natural history of intermediate risk prostate cancer is imperfect. While the benefits of AS make it an appealing option for men with intermediate risk disease, the published experience todate demonstrates that AS for all men with intermediate risk disease leads to higher rates of metastatic disease and loss of the opportunity for cure. These same studies also demonstrate that a subset of patients with intermediate risk disease have indolent disease that may benefit from AS. This heterogeneity is not adequately captured with traditional histopathologic staging. Clinical, genomic, and radiologic biomarkers play a key role in appropriate risk stratification and patient selection. The optimal use of these biomarkers in the intermediate risk patient is currently the subject of intense evaluation. Conclusion: Active surveillance for men at the favorable end of intermediate risk prostate cancer is an appealing alternative to radical therapy, but carries a modest but increased risk of metastatic disease compared to low risk cancer. Many biomarkers are currently being evaluated to enhance precise risk stratification of this important subgroup of patients

Future developments in ureteral stents.

PURPOSE OF REVIEW: We present a review of recent literature to summarize the most recent evidence on the use of ureteral stents, including the use of different materials and treatment of stent-related symptoms. RECENT FINDINGS: Metal stents are able to resist lumen occlusion from extrinsic compression allowing longer indwelling time and making them an option for long-term use. Biodegradable stents have the advantage not to require secondary procedures; however, they have not proven their safety in the clinical setting yet. Coated and drug-eluting stents seem to be promising concepts to prevent stent-related symptoms, but still have to be considered as experimental approaches. The most commonly used stent type is the standard double J stent, named for its J-shaped curled ends and manufactured from polyurethane, silicone or various polymers. SUMMARY: After more than 5 decades of using stents there are promising advancements in their designs and materials aiming to maintain their patency and control stent-related symptoms. Long-term metallic stents and coated stents are good options that should be considered in selected patients. Biodegradable stents are promising developments but not sophisticated yet. Pain medication, alpha-blocker and antimuscarinic medications are still frequently used and necessary. Treatment combinations can result in better outcomes than monotherapy.

The who, when, and why of primary adrenal malignancies: Insights into the epidemiology of a rare clinical entity.

BACKGROUND: Primary malignancies of the adrenal glands are rare. Epidemiologic assessment of primary adrenal malignancies is lacking and has been limited to case reports and series. Population-level data can provide a better understanding of the incidence, distribution, and prognostic factors associated with these rare malignancies. METHODS: The Surveillance, Epidemiology, and End Results database (1973-2013) was queried for all patients who were diagnosed with primary adrenal malignancies, categorized in 5 histologic groups: adrenocortical carcinoma (ACC), pheochromocytoma and paraganglioma (PH), neuroblastoma (NE), non-Hodgkin lymphoma (NHL), and sarcoma (SA). Age-adjusted incidence, distribution trends, and cancer-specific survival (CSS) for each group were analyzed. RESULTS: In total, 4695 patients with primary adrenal malignancies were identified, including 2057 with ACC, 512 with PH, 1863 with NE, 202 with NHL, and 61 with SA. The age-adjusted incidence of all 5 histologic subtypes was rising. Age at presentation differed substantially by histologic group: NE was the most prevalent during the first decade of life, whereas ACC predominated after age 30 years, and NHL outnumbered PH after age 70 years. Patient-specific factors were not associated with advanced disease at the time of presentation. The 5-year CSS rate for each histologic subtype was 38% for ACC, 69% for PH, 64% for NE, 38% for NHL, and 42% for SA. Survival outcomes for patients with ACC, NHL, PH and SA remained unchanged over the 40-year study period. Multimodal therapy was associated with higher CSS in patients with NE. CONCLUSIONS: This first population-level analysis of all primary adrenal malignancies provides important initial data regarding presentation and clinical outcomes. Notably, except for patients with NE, the survival of patients with these rare cancers has not improved over the past 40 years.

Renal tumor biopsy: indicators, technique, safety, accuracy results, and impact on treatment decision management.

CONTEXT: Renal tumor biopsy (RTB), as distinct from the more common renal biopsy for medical renal disease, is an option for patients with renal masses. It is mainly used for small renal masses (SRM) but it may also be indicated for larger masses and even in the presence of metastatic disease. Its main indication in SRM is to avoid intervention for benign kidney tumors but increasingly enables more personalized treatment for kidney cancer patients. OBJECTIVE: The objective of this paper is to provide a comprehensive review of the most recent literature available for RTB including the indications, the technique and also the possible complications. RESULTS: The urological community continues to optimize the indications for RTB. Non-operative treatment modalities, such as active surveillance, ablative modalities, and immunotherapy, may have different results influenced by tumor histology. Continuing concern regarding complications and accuracy and, therefore, the utility of RTB has been addressed. Recent reports support the potential benefit of RTB, safely avoiding a significant number of interventions with good results and minimal complications. CONCLUSION: Urologists should be aware of the benefits of RTB and develop experience with this technique to optimize the results. This diagnostic strategy should be discussed with patients and adopted as it has been with other solid tumors.