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.

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.

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.

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.

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.

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.

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.

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.