Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD).

BACKGROUND: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled. METHODS: The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12-item measure) assessed immediately after a urology consultation. RESULTS: Four sites administered the previsit DA (39 patients), 4 sites administered the within-visit DA (44 patients), 3 sites administered both previsit and within-visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within-visit DA study arm, 67% for the previsit DA only arm, 58% for the within-visit DA only arm, and 58% for the usual-care arm. Neither the previsit DA nor the within-visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively). CONCLUSIONS: DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge.

Diminished long-term recovery of peak flow rate (PFR) after robotic prostatectomy in men with baseline PFR <10 mL/s and incidental association with high-risk prostate cancer.

OBJECTIVE: The aim of this study was to evaluate the effects of robot-assisted radical prostatectomy (RARP) on uroflowmetry (UF) parameters among men with baseline peak flow rates (PFR) <10 mL/s. METHODS: A single-surgeon RARP database of 1082 men who underwent prospective UF testing was analyzed. Men filled out International Prostate Symptom Score questionnaires and underwent uroflowmetry and post-void bladder ultrasound before surgery and at each follow-up visit. Patients were divided into 2 groups based on preoperative PFR: those with PFR <10 mL/s (n = 158) and those with PFR ≥10 mL/s (n = 924). Univariate and multivariate regression models tested the association of preoperative characteristics in predicting postoperative PFR improvement. Within the PFR <10 mL/s group, preoperative variables were analyzed to predict pathologic outcomes. RESULTS: Three months after RARP, men with baseline PFR <10 mL/s had a 3-fold improvement in PFR (from mean of 7.0 to 24.2 mL/s), whereas in men with PFR ≥10 mL/s there was a 50% improvement (from mean of 19.7 to 28.9 mL/s; P < .001). Improvement in PFR remained stable for >5 years, but mean postoperative PFR was 20% lower in men with baseline PFR <10 mL/s. Preoperative prostate-specific antigen (odds ratio [OR] 0.75; 95% confidence interval [CI] 0.59-0.95) and PFR (OR 0.52; 95% CI 0.34-0.80) were independent predictors of the percentage improvement in men with baseline PFR <10 mL/s. Preoperative PFR ≤7 mL/s was an independent predictor of Gleason score ≥8 (P = .016), seminal vesicle invasion (P = .010), and lymph node invasion (0.029). CONCLUSIONS: After RARP, PFR improved significantly, with the improvement persisting over long-term follow-up. However, men with baseline PFR <10 mL/s had a 20% lower postoperative PFR over 5 years, suggesting permanent damage to the bladder and the need for early treatment to maintain bladder health. There appears to be an association between baseline PFR ≤7 mL/s and adverse pathologic features.

Surgeon-led prostate cancer lymph node staging: pathological outcomes stratified by robot-assisted dissection templates and patient selection.

OBJECTIVES: To evaluate the perioperative, pathological, and oncological outcomes from surgeon-led pathological staging of pelvic lymph node (LN) metastases at the time of robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Over the 6-year period of 2006-2012, three distinct pelvic LN dissection (PLND) strategies were used in chronological order at a single cancer referral hospital. Strategies were characterised by both an omission of PLND (pNx) vs inclusion decision threshold, and standard vs extended templates for patients selected for PLND. The three cohorts included: (i) omission vs standard template (04/2006-10/2007), for dominant Gleason score 4-5 or a prostate-specific antigen (PSA) level of >10 ng/mL; (ii) omission/standard vs extended template (11/2007-12/2010), for dominant Gleason score 4-5, PSA level of >10 ng/mL, any single core >7 mm, or >3 ipsilateral positive cores; and (iii) extended template with minimal exceptions (01/2011-08/2012). Standard outcomes data compared included: Clavien-Dindo complication rates, LN metrics (yield, percentage positive), and biochemical recurrence (BCR). A novel metric comprised 'pNx regret': the rate of pNx patients upgraded/upstaged. Exploratory analyses included selection criteria for reduced PLND templates, i.e. low-yield subsets. RESULTS: Standard PLND yielded 8-10 LNs and a positive-LN yield of 2.2-6.2%. The addition of an extended PLND (E-PLND) significantly increased the yield to 14-20 LNs and the positive-LN yield to 17.4-18.4% (both P < 0.001). E-PLND had the highest impact on the percentage of positive LNs (%pN1) for high-risk disease (9.3 vs 32.8%, P = 0.002), modest for intermediate risk (4.2 vs 10.9%, P = 0.003), and minimal impact on low risk disease (4.1 vs 0%, P = 0.401). The combined strategies of setting a very low threshold for E-PLND and sending separate LN packets increased the LN yields (18 vs 24, P < 0.001), but did not significantly change the observed %pN1 rates by clinical risk group (P = 0.975). Efforts to reduce the need for E-PLND included omission by clinical criteria, but resulting in 'pNx regret' in 16-19%. A third of patients with unilateral disease and positive LNs were found to have contralateral disease. A subset of men with minimal biopsy volume Gleason score 4 + 3 had pN1 rates after E-PLND of three of 14 (21%) compared to minimal biopsy volume Gleason score 3 + 4 pN1 rates after E-PLND of 0 of 31. E-PLND takes about twice as long to perform but with no statistically significant difference in complications (5.0 vs 6.0%, P = 0.511). The 5-year BCR rates were higher for E-PLND, given the selection criteria, but not different for overall survival. CONCLUSIONS: The net benefit of E-PLND remains uncertain, and therapeutic impact will probably require a randomised trial, given the strong selection criteria. E-PLND contributes to oncological staging in a significant number of high- and intermediate-risk patients, and should be bilateral. Immediate concerns include longer operative times, but no higher complication rates.

Salvage Percutaneous Cryoablation for Locally Recurrent Renal-Cell Carcinoma After Primary Cryoablation.

BACKGROUND: The management of locally recurrent renal-cell carcinoma (RCC) following cryoablation remains a clinical dilemma. There is limited data regarding the management of locally recurrent disease in the setting of patients who have failed initial percutaneous cryoablation (PCA). We evaluate and report our experience with salvage PCA for local recurrence following renal cryoablation failure. PATIENTS AND METHODS: We reviewed our experience with patients who underwent salvage PCA for local biopsy proven RCC recurrence following primary cryoablation procedures. Complications and oncologic outcomes were evaluated. Recurrence-free survival after primary and repeat cryoablation was plotted using the Kaplan-Meier curves. RESULTS: A total 250 patients underwent primary cryoablation for RCC and 20 (8%) patients were identified who underwent repeat PCA for 21 locally recurrent tumors. The mean tumor size was 2.4 cm. Biopsy revealed clear cell in 14 patients, three papillary and four chromophobe RCC. All repeat cryoablation procedures were completed successfully, with no treatment failures on postprocedure imaging. There were no complications or deaths. With the median follow-up of 30 months (range 7-63), 3 (15%) patients experienced local recurrence. One patient had an enhancing lesion at 13 months following repeat PCA and underwent a third PCA. Two patients had recurrence at 6 and 35 months respectively and underwent successful laparoscopic partial nephrectomy. Local recurrence-free, metastasis-free and cancer-specific survival rates were 85%, 100%, and 100% respectively. Limitations include retrospective design and small number of patients. CONCLUSIONS: Repeat PCA after primary cryoablation failure is feasible, has a low complication rate, and acceptable short-term oncologic outcomes. Further studies with durable follow-up are required.

Active surveillance for prostate cancer: when to recommend delayed intervention.

There are no agreed upon guidelines for placing patients on active surveillance (AS). Therefore, there are no absolute criteria for taking patients off AS and when to recommend treatment. The criteria used to define progression are currently based on prostate specific antigen (PSA) kinetics, biopsy reclassification, and change in clinical stage. Multiple studies have evaluated predictors of progression such as PSA, PSA density (PSAD), prostate volume, core positivity, and visible lesion on multiparametric magnetic resonance imaging (mpMRI). Furthermore, published nomograms designed to predict indolent prostate cancer do not perform well when used to predict progression. Newer biomarkers have also not performed well to predict progression. These findings highlight that clinical and pathologic variables are not enough to identify patients that will progress while on AS. In the future, with the use of imaging, biomarkers, and gene expression assays, we should be better equipped to diagnose/stage prostate cancer and to distinguish between insignificant and significant disease.

Analysis of Improved Urinary Peak Flow Rates After Robot-Assisted Radical Prostatectomy.

PURPOSE: Longitudinal assessment of prostatic obstruction has historically been assessed with urinary peak flow rates (PFR). In this observational study, we assess the impact of prostate removal on preoperative and postoperative PFRs after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: A single surgeon (TA) performed RARPs between 2002 and 2007. Men underwent routine preoperative uroflowmetric testing: 550 qualified for analysis with a sufficient voided volume (VV) of 150 mL preoperatively and at least once postoperatively. Continence and self-assessed American Urological Association (AUA) symptom and urinary quality of life (QoL) questionnaires were queried. Uroflows were analyzed preoperatively, short-term (3-15 mos), long-term (>2 y), and by age decades, lower urinary tract symptoms (LUTS) groups, and pathologic weight cohorts. RESULTS: AUA and QoL scores improved from 8.1 and 1.6 at baseline to 4.4 and 1.0 at intermediate-term follow-up, P<0.01. Mean PFRs improved from a baseline 18.0 mL/s to 28.3, 30.8, and 36.5 at 3 months, 9 months, and >5 years follow- up (all P<0.001). Postvoid residual (PVR) volumes declined from 99 mL preoperatively to 24 mL at >5 years (P<0.01). Likewise, all age, LUTS, and prostate weight cohorts had significant improvements in PFR and PVR and stable voided volumes throughout the study. CONCLUSION: The natural history of prostatic obstruction for men 40 to 80 years typically reveals reduction of mean PFRs. We observed that removal of the prostate resulted on average with a near doubling of PFRs and decreased PVRs (>50%) by 3 months. After RARP, the average PFR was reset to 25-30 mL/s, and these results were seen across all age, LUTS, and prostate weight groups; the gains remained stable 2 to 4 years after operation.

Clinical outcomes of patients with nondiagnostic biopsy during cryoablation of small renal masses.

OBJECTIVE: To compare the outcomes of patients with biopsy-proven renal cell carcinoma (RCC), benign tumors (BTs), and nondiagnostic (ND) biopsies after renal cryoablation (RC). METHODS: We retrospectively reviewed medical records of 114 patients who underwent RC between 2003 and 2013. Patients were stratified according to biopsy histopathology results-RCC, BT, and ND biopsy. We recorded patient demographics and tumor features and examined oncologic outcomes among the 3 groups. RESULTS: RC was performed in 114 patients with 117 tumors. Seventy-two tumors (61.5%) were RCC, 18 (15.4%) were BTs (oncocytoma or angiomyolipoma), and 27 (23.1%) were ND. Patient characteristics and tumor features were similar among the 3 groups. The median follow-up was 26.5, 26.0, and 22.0 months in the RCC, BT, and ND biopsy groups, respectively (P = .18). Residual disease occurred in the RCC (1.4%) and ND biopsy (7.4%) groups, but not in the BT group (P = .19). All 9 patients (12.5%) who developed recurrent disease had biopsy-proven RCC. The 2- and 5-year recurrence-free survival rates (RFS) for patients with biopsy-proven RCC were 90.2% and 81.2%, respectively. Because no patient in the BT and ND biopsy groups had a recurrence, their RFS was 100%. CONCLUSION: No patient with a BT or ND biopsy developed a local recurrence with short-term follow-up, whereas a recurrence developed in 12.5% of biopsy-proven RCC tumors. RFS for patients with biopsy-proven RCC was worse than the other 2 biopsy groups, although not statistically significant. Long-term follow-up in a larger cohort of patients is needed to further evaluate these preliminary findings.

Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: Natural history and outcomes after surgical resection with curative intent.

PURPOSE: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. Although existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate postnephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. PATIENTS AND METHODS: An institutional review board-approved review from 1986 to 2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy, and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. RESULTS: OS for the entire cohort (n = 77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who has NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and recurrence-free survival. Limitations include the retrospective nature of this study and relatively small sample size. CONCLUSIONS: Long-term survival for patients with sRCC, even in clinically localized disease, is poor. Aggressive surveillance of those who have NED following nephrectomy is essential, and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted.

Preoperative predictors of pathological lymph node metastasis in patients with renal cell carcinoma undergoing retroperitoneal lymph node dissection.

PURPOSE: Patients with locally advanced renal cell carcinoma represent a subset that may benefit from retroperitoneal lymph node dissection. We identified preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma without distant metastasis who underwent retroperitoneal lymph node dissection. MATERIALS AND METHODS: We retrospectively analyzed data on a consecutive cohort of 1,270 patients with cTany Nany M0 renal cell carcinoma who were treated at a single institution from 1993 to 2012. Multivariate analysis was performed to determine preoperative predictors of pathologically positive lymph nodes in patients who underwent retroperitoneal lymph node dissection. A nomogram was developed to predict the probability of lymph node metastasis. Overall, cancer specific and recurrence-free survival was estimated using the Kaplan-Meier Method. RESULTS: We identified 1,270 patients with renal cell carcinoma without distant metastasis who had (564) or did not have (706) retroperitoneal lymph node dissection performed. Of the 564 patients 131 (23%) and 433 (77%) had pN1 and pN0 disease, and 60 (37%) and 29 (7.2%) had cN1pN0 and cN0pN1 disease, respectively. ECOG PS, cN stage, local symptoms and lactate dehydrogenase were associated with nodal metastasis on multivariable analysis. A nomogram was developed with a C-index of 0.89 that demonstrated excellent calibration. Differences in overall, cancer specific and recurrence-free survival among pNx, pN0 and pN1 cases were statistically significant (p <0.001). CONCLUSIONS: Local symptoms, ECOG PS, cN stage and lactate dehydrogenase were independent predictors of lymph node metastasis in patients who underwent retroperitoneal lymph node dissection. Our predictive nomogram using these factors showed excellent discrimination and calibration.

A comparative analysis of complications after robot-assisted radical prostatectomy for men aged ≤69 and ≥70 years.

BACKGROUND AND PURPOSE: Robot-assisted radical prostatectomy (RARP) is a popular treatment option for localized prostate cancer. Literature is lacking on the effect of advanced age on complication rates in men undergoing robotic prostatectomy. We performed a comparative analysis of complication rates for men ≤69 and ≥70 years undergoing RARP. METHODS: After IRB approval, we reviewed our initial 1000 consecutive patients who underwent RARP from 6/2002 to 6/2011 for intraoperative and postoperative complications, and we compared complication rates stratified by age ≤69 and ≥70 years. Complications were graded according to the Clavien-Dindo classification system. The Fischer's exact test was used to compare complication rates, and a p-value of <0.05 was considered statistically significant. RESULTS: In our cohort, 868 men were ≤69 and 129 men were ≥70. Overall, the intraoperative and postoperative complication rates for the entire cohort were 0.90% and 10.2%, respectively. There was no statistically significant difference in individual postoperative complications between the two groups, however, the overall postoperative complications rates for men ≤69 and ≥70 were 9.4% and 15.4%, respectively (p-value=0.043). Major complication rates for men ≤69 and ≥70 were 6.7% (58) and 10.8% (14), respectively (p=0.10); minor complications rates were 2.8% (22) and 4.6% (6), respectively (p=0.25). CONCLUSIONS: In our study, men ≥70 had a significantly higher overall complication rate after RARP compared with men ≤69 years; however, the individual, minor, and major complications were not different between the two groups. RARP is relatively safe in this older age group. Identifying complications and proposing insightful working solutions have decreased both minor and major complication rates after RARP.

Comparison of radiation dose from conventional and triple-bolus computed tomography urography protocols in the diagnosis and management of patients with renal cortical neoplasms.

OBJECTIVE: To retrospectively compare the radiation dose of triple-bolus computed tomography (TBCT) and conventional CT (CCT) urography protocols, analyze the effects of body mass index (BMI) on radiation dose in each group, and assess image quality. MATERIALS AND METHODS: We retrospectively reviewed the images of patients who underwent CCT or TBCT imaging in the management of renal cortical neoplasms. We used standard volumetric CT dose index (CTDIvol) and dose length product (DLP) to estimate radiation exposure. In addition, 2 urologists rated the quality of 20 CT images from each group using a survey with a 5-point Likert scale. The survey consisted of 10 questions relating to the ability of the scan to identify relevant renal anatomy. RESULTS: The study included 120 patients. CTDIvol and DLP were 28.7% and 40.4% lower in the TBCT protocol, respectively (both P < .001). Increased BMI was associated with a higher DLP for the CCT group compared with the TBCT group (P < .001). The effect of BMI on CTDIvol did not differ between the CCT and TBCT groups. There was no difference in the urologists' assessments of CT image quality. CONCLUSION: In patients with renal cortical neoplasms, TBCT provides comparable image quality to CCT, with lower ionizing radiation exposure without compromising image quality. Obese patients may benefit more from TBCT scans.

Partial nephrectomy in the setting of metastatic renal cell carcinoma.

PURPOSE: Cytoreductive nephrectomy remains the standard of care for appropriately selected patients with metastatic renal cell carcinoma. Although the role of partial nephrectomy is well accepted in patients with localized disease, limited data are available on partial nephrectomy in the metastatic setting. We identified the indications for and outcomes of partial nephrectomy in the setting of metastatic renal cell carcinoma with particular attention to partial nephrectomy subgroups. MATERIALS AND METHODS: We analyzed data on a consecutive cohort of 33 patients with metastatic renal cell carcinoma who underwent partial nephrectomy at a single institution between 1996 and 2011. Nonparametric statistics were used to compare partial nephrectomy subgroups. Overall survival was estimated using the Kaplan-Meier method and survival functions were compared using the log rank test. RESULTS: At presentation 8 patients had bilateral synchronous renal masses, 20 had a metachronous contralateral renal mass and 5 had a unilateral renal mass. A total of 22 patients (67%) died of disease a median of 27 months postoperatively. Patients who underwent partial nephrectomy for a metachronous contralateral renal mass and a renal mass 4 cm or less had the best overall survival (61 and 42 months, respectively). Median overall survival in patients with vs without metastatic disease at original diagnosis was 27 vs 63 months (p = 0.003). CONCLUSIONS: Our findings suggest that metastasis at the original diagnosis and the timing of presentation of the partial nephrectomy index lesion have an important role in survival. These factors should be considered when determining which patients would benefit from partial nephrectomy in the setting of metastatic renal cell carcinoma.

Autotaxin-lysophosphatidic acid signaling axis mediates tumorigenesis and development of acquired resistance to sunitinib in renal cell carcinoma.

PURPOSE: Sunitinib is currently considered as the standard treatment for advanced renal cell carcinoma (RCC). We aimed to better understand the mechanisms of sunitinib action in kidney cancer treatment and in the development of acquired resistance. EXPERIMENTAL DESIGN: Gene expression profiles of RCC tumor endothelium in sunitinib-treated and -untreated patients were analyzed and verified by quantitative PCR and immunohistochemistry. The functional role of the target gene identified was investigated in RCC cell lines and primary cultures in vitro and in preclinical animal models in vivo. RESULTS: Altered expression of autotaxin, an extracellular lysophospholipase D, was detected in sunitinib-treated tumor vasculature of human RCC and in the tumor endothelial cells of RCC xenograft models when adapting to sunitinib. ATX and its catalytic product, lysophosphatidic acid (LPA), regulated the signaling pathways and cell motility of RCC in vitro. However, no marked in vitro effect of ATX-LPA signaling on endothelial cells was observed. Functional blockage of LPA receptor 1 (LPA1) using an LPA1 antagonist, Ki16425, or gene silencing of LPA1 in RCC cells attenuated LPA-mediated intracellular signaling and invasion responses in vitro. Ki16425 treatment also dampened RCC tumorigenesis in vivo. In addition, coadministration of Ki16425 with sunitinib prolonged the sensitivity of RCC to sunitinib in xenograft models, suggesting that ATX-LPA signaling in part mediates the acquired resistance against sunitinib in RCC. CONCLUSIONS: Our results reveal that endothelial ATX acts through LPA signaling to promote renal tumorigenesis and is functionally involved in the acquired resistance of RCC to sunitinib.

Analysis of urological procedures in men who died from prostate cancer using a population-based approach.

UNLABELLED: What's known on the subject? and What does the study add? Very few studies have examined end-of-life urological studies in men with prostate cancer. These studies reported fewer procedures in men who received primary therapy for prostate cancer. However, these studies were typically single institution or had a short follow-up period. The present study is the first population-based study examining end-of-life urological procedures and uses a geographic region encompassing 385 000 patients. Furthermore, this study incorporates both hospital- and office-based procedures. This approach has not been previously undertaken. OBJECTIVE: To determine using a population-based approach whether men with end-stage prostate cancer who had definitive primary therapy might require fewer urological interventions. Repeated urological procedures can impact health-related quality of life in patients dying from prostate cancer. PATIENTS AND METHODS: Using the Marshfield Epidemiological Study Area (MESA) database and tumour registry, we compared end-of-life interventions in men who died from prostate cancer between 1991 and 2009. Patient charts were queried for urological procedures using International Classification of Disease Modification, 9th edition (ICD9) codes for 3 years before death. Clinicopathological information was examined including whether the patient had a history of primary therapy (radiation or radical prostatectomy). RESULTS: Among 280 patients dying from prostate cancer, 52 (19%) required 153 urological procedures during the last 3 years of life. The frequency of procedures increased closer to death. The most common procedures involved nephrostomy tube (56%), Foley catheter (24%) and transurethral resection of the prostate (10%). Clinicopathological features did not predict the need for an end-of-life urological procedure. There was no difference in the frequency of upper or lower tract procedures in surgery or radiation patients compared with patients without primary therapy (P = 0.556 and P = 0.508). Using a Kaplan-Meier analysis, there were no differences between groups in the proportion of patients not requiring a procedure (n = 280; P = 0.179). CONCLUSIONS: This is the first population-based study to examine the frequency of urological procedures in patients with end-stage prostate cancer. A minority of patients (19%) required urological procedures during the final 3 years of life. A history of surgery or radiation did not influence the overall risk for urological intervention.

Chromosomal abnormalities in 2 cases of testicular failure.

This study investigated the underlying chromosomal abnormalities of testicular failure using molecular cytogenetic analysis. We report 2 cases of rare genetic anomalies that resulted in hypogonadism. The first patient presented with severe hypogonadism. Chromosome analysis revealed a mosaic 46,X,r(Y) (p11.3q11.23)/45,X karyotype, with a ring Y chromosome. A Y chromosome microdeletion assay showed a deletion in the azoospermia factor a region. The second patient presented with infertility and nonobstructive azoospermia. Cytogenetic and fluorescent in situ hybridization analysis revealed a 47,XY,+mar.ish i(15) (D15Z1++,SNRPN2,PML2) karyotype, with a small supernumerary chromosome derived from chromosome 15. These results emphasize the need for molecular cytogenetic evaluation in patients with testicular failure before using advanced reproductive techniques.

Effect of prostate volume on tumor grade in patients undergoing radical prostatectomy in the era of extended prostatic biopsies.

PURPOSE: We investigated the influence of prostate volume on biopsy and prostatectomy Gleason score, the incidence of upgrading and total tumor volume. MATERIALS AND METHODS: From 1997 to 2004, 247 patients were diagnosed with prostate cancer by multisite extended prostatic biopsy (10 or 11 cores) and underwent radical prostatectomy at our institution without neoadjuvant therapy. Medical records were reviewed to determine patient age at diagnosis, preoperative prostate specific antigen, prostate volume, clinical stage, biopsy Gleason score, pathological stage, prostatectomy Gleason score and total tumor volume. The Mann-Whitney and chi-square tests were used to compare variables among groups and multivariate regression analysis was used to determine predictors of Gleason score. RESULTS: Median patient age was 61 years and median preoperative prostate specific antigen was 5.5 ng/ml. Median prostate volume on transrectal ultrasound was 37 cc. Prostatectomy Gleason score was 6 in 31% of cases, 7 in 57% and 8-9 in 12%. Prostate volume greater than 50 cc was significantly associated with a higher incidence of well differentiated tumors (Gleason score 6) at prostatectomy, that is 17.9% in patients with a prostate volume of 25 cc or less, 28.9% in those with a prostate volume of 25 to 50 cc and 45.3% in those with a prostate volume of greater than 50 cc (p<0.01). In addition, the incidence of tumor upgrading was significantly lower in patients with a large prostate volume (greater than 50 cc) compared to that in those with a smaller prostate volume (20.8% vs 36.1%, p<0.05), particularly in the subset with biopsy Gleason score 6 (24% vs 54.1%, p<0.01). Patients with a large prostate volume (greater than 50 cc) had smaller total tumor volume with a trend toward statistical significance (median total tumor volume 0.86 vs 1.1 cc, p=0.0631). CONCLUSIONS: In the era of extended prostatic biopsies patients with a large prostate volume have a significantly higher incidence of well differentiated tumor at prostatectomy and a lower likelihood of tumor upgrading.

Identification of factors predicting response to adjuvant radiation therapy in patients with positive margins after radical prostatectomy.

PURPOSE: Radical prostatectomy (RP) is a highly effective treatment for patients with prostate cancer. However, patients with positive surgical margins after radical prostatectomy have less than ideal outcomes with 5-year progression rates between 36% and 50%. Postoperative radiation therapy (RT) is often advocated for improving these outcomes. We identified predictors of response to adjuvant RT given for positive margins after RP. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of men who underwent RP between 1987 and 1999 at our institution and who received adjuvant RT for positive surgical margins. Only patients in whom prostate specific antigen (PSA) was undetectable after RP as well as before the initiation of RT were included. Numerous clinicopathological variables, including pre-RP PSA, pathological stage, margin length and location, and extracapsular extension or seminal vesicle involvement, were assessed for their adverse effect on the biochemical recurrence rate after adjuvant RT. RESULTS: A total of 62 men met our inclusion criteria. Median age at surgery was 60.7 +/- 6.1 years and median PSA at presentation was 9.0 ng/ml (range 1.4 to 64.9). The median RT dose was 60.0 +/- 3.6 Gy. RT was started a median of 5.0 +/- 3.6 months after RP. The 5 and 10-year biochemical disease-free survival rates for the whole group were 90.2% and 87.9%, respectively. Of all parameters tested only Gleason score 4 + 3 or greater (p = 0.037) and pre-RP PSA greater than 10.9 ng/ml (p = 0.040) were predictive of biochemical recurrence after adjuvant RT on univariate analysis. On multivariate analysis only pre-RP PSA greater than 10.9 ng/ml remained an independent predictor (p = 0.031). CONCLUSIONS: In the setting of true adjuvant RT in patients with positive margins after RP and undetectable PSA those with predominant Gleason grade 4 or greater, or PSA greater than 10.9 ng/ml at presentation are at increased risk for recurrence after adjuvant RT.