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Objective Guidelines for muscle-invasive bladder cancer (MIBC) recommends that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) program have been poorly described. Methods Using the SEER database, we collected data of MIBC according to the American Joint Commission on Cancer (AJCC). We considered differences in patient demographics and tumor characteristics based on three treatment groups: Chemotherapy (both adjuvant and neoadjuvant) with radical cystectomy, radical cystectomy, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends were included for each treatment group. Kaplan–Meier curves were performed to compare cause-specific survival. A Cox proportional-hazards model was utilized to describe predictors of survival. Results Of 16 728 patients, 10 468 patients received radical cystectomy alone, 3236 received chemotherapy with radical cystectomy, and 3024 received chemoradiotherapy. Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American; stage III patients tended to be divorced. Patients who received chemotherapy with radical cystectomy tended to be males; stage II patients were less likely to be Asian than White. Stage III patients were less likely to receive chemoradiotherapy as a treatment option than stage II. Chemotherapy with radical cystectomy and chemoradiotherapy are both underutilized treatment options, though increasingly utilized. Kaplan–Meier survival curves showed significant differences between stage II and III tumors at each interval. A Cox proportional-hazards model showed differences in gender, tumor stage, treatment modality, age, and marital status. Conclusions Radical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends. Significant disparities exist in those who receive radical cystectomy over chemoradiotherapy for treatment.

Purpose: Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether soluble B7-H1 (sB7-H1) levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome.Experimental Design: We developed an ELISA for quantification of sB7-H1 in biological fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein microsequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T-cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome.Results: sB7-H1 was detected in the cell supernatants of some B7-H1–positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver proapoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (P < 0.001), tumors of advanced stage (P = 0.017) and grade (P = 0.044), and tumors with necrosis (P = 0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (P = 0.010).Conclusion: Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome. Clin Cancer Res; 17(7); 1915–23. ©2011 AACR.

Supplementary Table S1 details the list of primers and their sequence used in this study.

This contains supplementary figures 1-4. Figure S1 displays H19 mRNA expression quantification and bodyweight measurements of additional phenotypes in the study. The data relates to Figure 1. Figure S2 contains additional IHC measurements for experimental mice for p-ERK and p-AKT. Figure S2 also contains apoptosis quantification data by TUNEL assay. These data relate to Figure 4 of the main text. Figure S2 also conatains mRNA expression measurements of proliferation related genes, related to Figure 5. Figure S3 conatains characterization data of Insulin receptor isoform expression and Igf1-receptor expression in experimental mouse prostates. Figure S4 contains additional data pertaining to human prostate IHC for IGF2, pERK, and pAKT expression, including correlation of these markers in prostate cancer and the average levels in various prostate tissue pathologies. This figure is related to Figure 5 of the main text.

Loss of imprinting (LOI) is an epigenetic event that relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor IGF2, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between IGF2 LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF-binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI. We found that Igf2 LOI increased the prevalence and severity of prostatic intraepithelial neoplasia (PIN), a premalignant lesion. Engineering Nkx3.1 deficiency into our model increased the frequency of PIN lesions in an additive fashion. Prostates harboring LOI displayed increased MAPK signaling and epithelial proliferation. In human prostate tissue arrays, we documented a positive correlation in benign tissues of IGF2 levels with phospho-ERK and phospho-AKT levels. Overall, our results establish that Igf2 LOI is sufficient on its own to increase rates of neoplastic development in the prostate by upregulating critical cancer-associated signaling pathways. Cancer Res; 77(19); 5236–47. ©2017 AACR.

Supplementary Figures S1-S5; Supplementary Materials and Methods.

Supplementary Figures 1-6 from B7-H3 Ligand Expression by Prostate Cancer: A Novel Marker of Prognosis and Potential Target for Therapy

B7 coregulatory ligands can be aberrantly expressed in human disease. In the context of cancer, these ligands may act as antigen-specific inhibitors of T-cell–mediated antitumoral immunity. We recently reported that B7-H1 expression by carcinomas of the kidney and bladder portends aggressive disease and diminished survival. The expression of these proteins in prostate cancer, however, has not been investigated. We evaluated B7-H3 and B7-H1 protein expression in the pathologic specimens of 338 men treated for clinically localized prostate cancer between 1995 and 1998 with radical retropubic prostatectomy. Expression levels of B7-H3 in prostate cancer were correlated with pathologic indicators of aggressive cancer as well as clinical outcome. We report that B7-H3 is uniformly and aberrantly expressed by adenocarcinomas of the prostate, high-grade prostatic intraepithelial neoplasia, and four prostate cancer cell lines, whereas B7-H1 is rarely expressed. B7-H3 is expressed by benign prostatic epithelia, although at a more reduced level relative to neoplastic tissue. Increasing levels of B7-H3 intensity correlate with worsening clinicopathologic features of prostate cancer. Marked B7-H3 intensity, present in 67 (19.8%) specimens, confers a >4-fold increased risk of cancer progression after surgery (risk ratio, 4.42; P < 0.001). A survey of normal tissues revealed that B7-H3 is expressed within the liver, urothelium, and fetal kidney. In summary, B7-H3 is aberrantly expressed in all prostate cancers and represents an independent predictor of cancer progression following surgery. Moreover, B7-H3 encompasses a novel diagnostic and potential therapeutic target for the clinical management of prostate cancer and, perhaps, other malignancies as well. [Cancer Res 2007;67(16):7893–900]

Salvage cystectomy is required for some patients with intravesical recurrence after trimodality therapy. We compared postoperative outcomes between salvage cystectomy post-trimodality therapy, primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy.We included 265 patients who underwent radical cystectomy at Massachusetts General Hospital for cT1-T4 bladder cancer between 2003 and 2013. Patients were grouped as salvage cystectomy post-trimodality therapy, primary cystectomy or primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Early (≤90 days) and late (90 days) complications were compared. Disease-specific survival and overall survival were calculated using a Cox regression model, and adjusted survival curves were generated.The median followup from the time of cystectomy was 65.5 months. There was no difference in intraoperative and early complications between the groups. The detection of late complications was higher in salvage cystectomy post-trimodality therapy compared to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy (p=0.03). In multivariable Cox regression analysis, salvage cystectomy post-trimodality therapy was associated with a higher incidence of any late (HR 2.3, p=0.02) and major late complications (HR 2.1, p0.05). There was no difference in disease-specific survival (p=0.8) or overall survival (p=0.9) between the groups.Salvage cystectomy post-trimodality therapy for intravesical recurrence post-trimodality therapy has an intraoperative and early complication rate comparable to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Salvage cystectomy post-trimodality therapy is associated with a higher risk of overall and major late complications than primary cystectomy. The disease-specific survival and overall survival of patients who require salvage cystectomy post-trimodality therapy are comparable to both groups.

Chronic BK polyomavirus (BKPyV) infection is recognized as a potential oncogenic factor of urothelial carcinoma (UC) in renal transplant recipients. Recent studies have reported a positive correlation among BKPyV integration, persistent overexpression of viral large T antigen (TAg), and malignancy, yet little is known about the specific integration mechanisms and the impacts of viral integration. Here, we performed whole-genome sequencing (WGS) and viral capture-based sequencing on high-grade immunohistochemically TAg-positive UCs in two renal transplant recipients. A total of 181 integration sites, including the three found by WGS, were identified by viral capture-based sequencing, indicating its enhanced sensitivity and ability in identifying low-read integration sites in subpopulations of the tumor cells. The microhomologies between human and BKPyV genomes were significantly enriched in the flanking regions of 84.5% the integration sites, with a median length of 7 bp. Notably, 75 human genes formed fusion sequences due to viral insertional integration. Among them, the expression of 15 genes were statistically associated with UC based on GEO2R expression analysis. Our results indicated a multisite and multifragment linear integration pattern and a potential microhomology or nonhomologous end joining integration mechanism at the single-nucleotide level. We put forward a potential selection mechanism driven by immunity and centered on viral integration in the carcinogenesis of BKPyV.

Objectives To identify the potential indicators for higher-risk disease and poor outcome in younger prostate cancer (PCa) patients (age ≤ 50) who had undergone radical prostatectomy (RP) in the prostate-specific antigen (PSA) era. Materials and methods A total of 186 PCa cases of age ≤ 50 who underwent RP between 2003 and 2010 at our center were included for study. High-risk disease after RP was defined as cases with pre-PSA ≥ 20 ng/ml and/or Gleason score (GS) ≥ 4 + 3 and/or pT stage ≥ 3. The poor outcome group was defined as cases with biochemical recurrence (BCR) and/or metastasis (Mets) and/or all-cause death. Multivariate logistic regression models were performed to identify independent risk factors for both high-risk disease and poor outcome. Results Among 186 younger PCa patients aged ≤ 50, 36 cases (19.5%) had high-risk disease and 24 cases (12.9%) had poor outcome. The presence of biopsy perineural invasion (BxPNI) was significantly associated with high-risk disease and showed a trend to correlate with worse outcome in univariate analysis. On multivariate logistic regression analysis, BxPNI was shown to be a significant independent risk factor with covariate of D'Amico for poor outcome (p = 0.047) and an independent risk factor with covariate of BxGPC for high-risk PCa excepting the variables to define high-risk disease (p = 0.013). Prognostically, cases with BxPNI showed a poor BCR-free survival in univariate analysis but did not reach significance (p = 0.063). Conclusion Our results show that BxPNI could be considered as a risk classification factor to identify the best candidates among younger PCa patients for further treatment and may also be used for developing active surveillance (AS) selection criteria for younger PCa patients.

Objectives With the rapid increase in younger age prostate cancer (PCa) patients, the impact of younger age on decision‐making for PCa treatment needs to be revaluated in the new era. Materials and Methods A systematic literature search was performed using PubMed, EMBASE, and Web of Science up to October 2019 to identify the eligible radical prostatectomy (RP) studies focusing on understanding the impact of age on clinicopathological features and oncological prognosis in patients with localized PCa in PSA era. Meta‐analyses were conducted using available hazard ratios (HRs) from both univariate and multivariate analyses. Results Twenty‐six studies including 391 068 patients with RP treatments from the PSA era were included. Of these studies, age of 50 years old (age50) is the most commonly used cut‐off age to separate the younger patient group (including either age, Younger age correlated with favorable clinicopathological characteristics and better BCR prognosis in low‐ to intermediate‐risk patients. In high‐risk group, younger patients often showed significantly worse oncological outcomes. Age 50 can be used as a practical cut‐off age to separate younger age patients from older age patients.

BK polyomavirus (BKPyV)-associated cancer after transplantation has gained increasing attention. However, the role of BKPyV integration on oncogenesis is still unclear. In this study, next-generation virome capture sequencing of primary and metastatic tumors were performed in three patients with BKPyV-associated urothelial carcinoma after renal transplantation. As a result, a total of 332 viral integration sites were identified in the six tumors. Integration of BKPyV in both primary and metastatic tumors followed the mechanism of microhomology-mediated end joining mostly, since microhomologies between human and BKPyV genomes were significantly enriched in flanking regions of 84% of the integration sites. Viral DNA breakpoints were nonrandom and tended to assemble in large T gene, small T gene and viral protein 2 gene. There were three, one and one consensus integration sites between the primary and metastatic tumors, which affected LINC01924, eIF3c, and NEIL2 genes in the three cases respectively. Thus, we concluded that integration of BKPyV was a continuous process occurring in both primary and metastatic tumors, generating heterogenous tumor cell populations. Through this ongoing process, certain cell populations might have gained growth advantage or metastatic potential, as a result of viral integration either affecting the cellular genes where the viral DNA integrated to or altering the expression or function of the viral genes.

INTRODUCTION AND OBJECTIVE:Prognostic models have been developed and validated to estimate survival in the setting of metastatic renal cell carcinoma (mRCC) using patient specific data, including t...

INTRODUCTION AND OBJECTIVE:Advancements in treatment strategies for metastatic renal cell carcinoma (mRCC) have led to a great variety of available targeted, immune checkpoint inhibitor (ICI), and ...

Objectives: To investigate the association between biopsy perineural invasion (PNI) and oncological outcomes of prostate cancer (PCa) after radical prostatectomy (RP).Materials and methods:...

Gleason grade (GG) on prostate biopsy is important for risk stratification and clinical decision making. Multiparametric MRI (mpMRI) improved detection of clinically significant disease and some studies suggest that MRI-fusion biopsy combined with systematic biopsy results in fewer upgrades on final surgical pathology. However, the downgrade rate is unclear and there is controversy in the literature. The objectives of this study are to assess the concordance of combination biopsy with final surgical pathology, and furthermore, to specifically determine downgrade rates.In our institutional mpMRI-ultrasound fusion biopsy database, 173 underwent targeted and systematic biopsy followed by radical prostatectomy (RP). GG on targeted, systematic and combination (targeted and systematic) biopsy were compared with GG on RP. Concordance rates between biopsy types were compared with the McNemar test. Proportion of GG upgrade or downgrade at the time of RP was also evaluated.Surgical pathology was concordant with 44.5% of systematic biopsies, 46.8% of targeted biopsies, and 56.7% of combination biopsies. Combination biopsy significantly overestimated the final GG on RP compared to systematic biopsy (16.8% vs. 8.7% RR 1.93, 95% CI 1.36-2.75, P0.001). Downgrade rate from unfavorable to favorable intermediate-risk disease was 46.2%, and from high-risk to intermediate-risk disease was 45.1%.Combination (targeted and systematic) biopsy is associated with the highest concordance rate between biopsy and RP pathology when compared with systematic or targeted biopsy alone. However, targeting MRI lesions and therefore the higher risk components, may at times overestimate the final surgical pathology which can result in overtreatment of what may truly be less aggressive disease.

Background: Guidelines for Muscle-Invasive Bladder cancer (MIBC) recommends that patients receive neoadjuvant chemotherapy with radical cystectomy or chemoradiotherapy, as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) have been poorly described. Methods: Using the SEER database, we collected data of MIBC according to the AJCC (American Joint Commission on Cancer). We considered differences in patient demographics and tumor characteristics based on three treatment groups: chemotherapy with radical cystectomy, radical cystectomy alone, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends of each treatment were compared. Results: Of 16,728 patients, 10,468 patients received radical cystectomy alone, 3,236 received radical cystectomy plus chemotherapy, and 3,024 received chemotherapy plus radiation. Patients who received chemoradiotherapy tended to be older and African American compared to radical cystectomy alone (

Objective The objective of this study was to evaluate the impact of the anterior/posterior status of positive surgical margin (PSM) on long-term outcomes after radical prostatectomy for prostate cancer. Patients and methods We included 391 consecutive PSM patients after radical prostatectomy between 1993 and 2007 excluding cases with multiple location PSM or lack of anterior/posterior status data. The oncologic impact of anterior-PSM and posterior-PSM were examined by Kaplan-Meier analysis and the Cox proportional hazards model. Results There were 115 cases (29.4%) with apex-PSM, 257 cases (65.7%) with peripheral PSM, and 19 cases (4.9%) with bladder neck PSM. Among the 257 peripheral PSM cases, 58 cases (22.6%) were with anterior-PSM, 174 cases (67.7%) were with posterior-PSM, and 25 cases (9.7%) were with both anterior and posterior PSM. Over a median follow-up of 12.6 years, patients with anterior-PSM, especially those with low to intermediate Gleason score (≤7), showed a biochemical recurrence (BCR) prognosis similar to those with apex-PSM. In contrast, patients with posterior-PSM showed significantly higher BCR risk on both univariate and multivariate analyses when compared with those with apex-PSM. No impact on metastasis-free survival or overall survival was observed. Conclusions In our study, we found that prostate cancer patients with anterior-PSM showed a more favorable BCR prognosis similar to those with apex-PSM when comparing to patients with posterior-PSM. Our study results may help physicians to choose different treatment options for patients diagnosed with different PSM status including considering further adjuvant treatment for patients with posterior-PSM.

Perineural invasion (PNI) after radical prostatectomy (RP) is a common feature of prostate cancer (PCa) and has been associated with unfavorable tumor characteristics. However, its prognostic relevance is controversial. In this study, we evaluated the impact of both PNI status (PNI+ versus PNI-) and quantified number of PNI focus on the long-term prognosis of biochemical recurrence (BCR) after RP. After reevaluating PNI of a total of 721 patients with localized PCa who underwent RP at our institution between 2000 and 2002, we examined associations between PNI status or PNI focus number and clinicopathological factors including tumor stage, Gleason score, margin status, tumor location, preoperative prostate specific antigen, age, prostate weight as well as BCR outcome. PNI was present in 530 of 721 cases (73.5%) of the RP specimens and was associated with more aggressive disease. BCR occurred in 19.4% of all patients within a median follow-up period of 8.5 years. PNI+ status was associated with poor BCR prognosis in univariate analysis but lost in multivariate analysis. Based on the number of PNI focus, PNI was further divided into 2 distinct group: PNI+ a (≤3) and PNI+ b (>3). In a multivariate Cox regression model, PNI+ b (>3) was identified as an independent BCR prognostic factor. Quantification of PNI focus number beside the dichotomized status recording will not only provide more detailed information but also be a novel prognostic indicator for risk stratification. Further external validation will be needed for an optimal cut-off value of the PNI focus number. Our findings will help further research on the relevance of PNI in the pretreatment setting and support ongoing efforts to understand its role of cancer progression.

OBJECTIVES: To develop and externally validate a model that quantifies the likelihood that a pathologically node-negative in a patient with clear cell renal cell carcinoma (cRCC) has, indeed, no Lymph node metastasis (LNM). PATIENTS AND METHODS: Data from 1389 patients treated with radical nephrectomy (RN) and lymph node dissection (LND) were analyzed. For external validation, we used data from 2270 patients in the Surveillance, Epidemiology and End Results (SEER) database. We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathological nodal staging score (pNSS), which represents the probability that a patient is correctly staged as node-negative as a function of the number of examined lymph nodes (LNs). RESULTS: The mean and median number of LNs removed were 7.0 and 5.0 (standard deviation, SD: 6.6, interquartile range, IQR: 7.0) in the development cohort and 5.6 and 2.0 (SD: 8.6, IQR: 5.0) in the validation cohort, respectively. The probability of missing a positive LN decreased with increasing number of LNs examined. In both the validation and the development cohort, the number of LNs needed for correctly staging a patient as node negative increased with higher pathological tumor stage and Fuhrman Grade. CONCLUSIONS: The number of examined LNs needed for adequate nodal staging in cRCC depends on pathological tumor stage and Fuhrman grade. We developed here and then externally validated a pNSS, which could help to refine patients counseling, decision-making regarding risk stratified surveillance regimens and inclusion criteria for clinical trials of adjuvant therapy.

OBJECTIVE We assessed whether type 2 diabetes is associated with renal cell carcinoma (RCC), independent of key potential confounders, in two large prospective cohorts with biennially updated covariate data. RESEARCH DESIGN AND METHODS A total of 117,570 women from the Nurses’ Health Study (NHS) and 48,866 men from the Health Professionals Follow-Up Study (HPFS) were followed from 1976 and 1986, respectively, through 2014. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs for associations between type 2 diabetes and pathology-confirmed RCC, overall and by stage, grade, and histologic subtype. RESULTS During 38 years of follow-up in the NHS, we confirmed 418 RCC case subjects, including 120 fatal cases. Over 28 years in the HPFS, we confirmed 302 RCC case subjects, including 87 fatal cases. Women with type 2 diabetes had a significantly increased risk of RCC compared with women without type 2 diabetes (multivariable HR 1.53; 95% CI 1.14–2.04), with some evidence that the association was stronger for ≤5 (HR 2.15; 95% CI 1.44–3.23) than >5 (HR 1.22; 95% CI 0.84–1.78) years’ duration of type 2 diabetes (Pdifference 0.03). Among men, type 2 diabetes was not associated with total RCC (HR 0.89; 95% CI 0.56–1.41) or with RCC defined by stage, grade, or subtype. Sample sizes for analyses by stage, grade, and subtype were limited. CONCLUSIONS We found that type 2 diabetes was independently associated with a greater risk of RCC in women but not in men.

Loss of imprinting (LOI) is an epigenetic event that relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor IGF2, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between IGF2 LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF-binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI. We found that Igf2 LOI increased the prevalence and severity of prostatic intraepithelial neoplasia (PIN), a premalignant lesion. Engineering Nkx3.1 deficiency into our model increased the frequency of PIN lesions in an additive fashion. Prostates harboring LOI displayed increased MAPK signaling and epithelial proliferation. In human prostate tissue arrays, we documented a positive correlation in benign tissues of IGF2 levels with phospho-ERK and phospho-AKT levels. Overall, our results establish that Igf2 LOI is sufficient on its own to increase rates of neoplastic development in the prostate by upregulating critical cancer-associated signaling pathways. Cancer Res; 77(19); 5236–47. ©2017 AACR.

Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus.Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models.A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02).We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials.

Background Trimodality bladder-sparing therapy (TMT) is an acceptable treatment for selected patients with muscle-invasive urothelial cancer. Outcomes of TMT in histologic variants remains largely unknown. Objective To compare outcomes of pure urothelial carcinoma (PUC) to variant urothelial carcinoma (VUC) after TMT. Design, setting, and participants Retrospective study of patients treated with TMT at a single cancer center from 1993 until 2013. Outcome measurements and statistical analysis Kaplan-Meier survival probabilities, and univariate and multivariable Cox regression analysis. Results and limitations Of 303 patients treated with TMT, 66 (22%) had VUC. Fifty (76%) had VUC with squamous and/or glandular differentiation and 16 (24%) had other forms. Complete response rate after induction TMT was 83% in PUC and 82% in VUC ( p =0.9). The 5-yr and 10-yr disease-specific survival (DSS) was 75% and 67% in PUC versus 64% and 64% in VUC. The 5-yr and 10-yr overall survival (OS) was 61% and 42% in PUC versus 52% and 42% in VUC. On multivariable analysis VUC was not associated with DSS (hazard ratio: 1.3, 95% confidence interval: 0.8–2.2, p =0.3) or OS (hazard ratio: 1.2, 95% confidence interval: 0.8–1.7, p =0.4). Salvage cystectomy rates were similar (log-rank p =0.3). Limitations include retrospective design and restriction to variants of urothelial cancer. Conclusions VUC responded to TMT, and there was no significant difference in complete response, OS, DSS, or salvage cystectomy rates compared with PUC. The presence of VUC should not exclude patients from TMT. Patient summary The response of histologic variants of bladder cancer to bladder-sparing chemoradiation is largely unknown. We compared the outcomes of histologic variants of urothelial cancer to pure urothelial cancer in a large series of patients from a single institution. We found that variant histology does not significantly influence outcomes.

Introduction To evaluate if moderate CKD (eGFR

Although surgical excision is the standard of therapy for small renal masses (SRMs), there is a growing recognition of active surveillance as an option in select patients who are poor surgical candidates or who have shorter life expectancy. A number of patients on expectant management, however, subsequently advance to definitive therapy. In this study, we systematically reviewed the literature and performed a pooled analysis of active surveillance series to evaluate the rate and indications for definitive treatment after initiating a period of active surveillance. Fourteen clinical series (1245 patients; 1364 lesions) met our selection criteria. Mean lesion size at presentation was 2.30 ± 0.40 cm with a mean follow-up of 33.6 ± 16.9 months. Collectively, 34.0% of patients underwent delayed intervention, which ranged in individual series from 3.6% to 70.3%. Of patients undergoing delayed intervention, the average time on active surveillance prior to definitive treatment was 27.8 ± 10.6 months. A pooled analysis revealed that 41.0% of patients underwent therapy secondary to tumor growth rate and 51.9% secondary to patient or physician preference in the absence of clinical progression. Overall, 1.1% of all patients progressed to metastatic disease during the average follow-up period. Thus, active surveillance may be an appropriate option for carefully selected patients with SRMs. However, delayed treatment is pursued in a significant percentage of patients within 3 years. Prospective registries and clinical trials with standardized indications for delayed intervention are needed to establish true rates of disease progressions and recommendations for delayed intervention.

A 19-year-old man presented with a 2-day history of hematuria, without pain, after hiking. Imaging revealed a well-circumscribed 4.6-cm retroperitoneal mass. A procedure was performed.

OBJECTIVE: To evaluate if body mass index (BMI) ≥ 40 is associated with risk of postoperative complications, receipt of perioperative blood transfusion (PBT), length of hospital stay (LOS), perioperative death, or hospital readmission rate following renal mass surgery. MATERIALS AND METHODS: After Institutional Review Board approval, comprehensive information was collected for patients treated with surgery for renal mass from 2000 to 2015 at one institution. Univariable and multivariable analyses were used to evaluate the association of BMI ≥ 40 among other putative risk factors for perioperative outcomes. RESULTS: A total of 1048 patients were treated surgically, including 115 (11%) with BMI > 40. Minimally invasive and open surgical approaches were used for 480 (45.8%) and 568 (54.2%) patients, respectively. Morbid obesity was not associated with risk of major complications, overall complications, receipt of PBT, LOS, hospital readmission rate, or perioperative death. Charlson comorbidity index was the only independent predictor of major complications following renal mass surgery, P = .0006, per point odds ratio 1.2 (95%C.I. 1.08–1.32). Surgical site infections (SSIs) were more common in patients with BMI ≥ 40 vs BMI < 40 (10.5% vs 4.8%, P = .01). Following multivariable analysis, BMI ≥ 40 was the only independent predictor of SSIs, odds ratio 2.6, 95% confidence interval 1.32–5.13; P = .006. CONCLUSION: Morbid obesity (BMI ≥ 40) is an independent predictor of developing SSIs following renal mass surgery. Morbid obesity is not predictive of risk for major complications, receipt of PBT, hospital readmission, perioperative death, or LOS.

There exists a growing debate as to whether multiparametric magnetic resonance imaging with fusion transrectal ultrasound guided prostate biopsy alone without a standard template biopsy is sufficient to evaluate patients with suspected prostate cancer. Our objective was to describe our experience with fusion targeted prostate biopsy and assess whether it could obviate the need for concomitant standard 12-core template prostate biopsy.We retrospectively reviewed our prospectively collected database of patients who underwent fusion transrectal ultrasound guided prostate biopsy. All images and lesions were graded according to the Prostate Imaging Reporting and Data System, version 2. All patients underwent targeted biopsy followed by standard 12-core double sextant biopsy within the same session. Clinically significant prostate cancer was defined as Grade Group 2 or greater prostate cancer.A total of 506 patients were included in analysis. Indications were elevated prostate specific antigen with a previous negative prostate biopsy in 46% of cases, prostate cancer on active surveillance in 35%, elevated prostate specific antigen without a prior prostate biopsy in 15% and an isolated abnormal digital rectal examination in 3%. For standard vs fusion prostate biopsy the overall cancer detection rate was 57.7% vs 54.0% (p=0.12) and the clinically significant prostate cancer detection rate was 24.7% vs 30.8% (p=0.001). Of the 185 patients diagnosed with clinically significant prostate cancer 29 (16%) would have been missed if only targeted fusion prostate biopsy had been performed.Fusion targeted prostate biopsy is associated with a higher detection rate of clinically significant prostate cancer compared to standard double sextant biopsy. However, standard double sextant biopsy should still be performed as part of the routine fusion targeted prostate biopsy procedure to avoid missing a significant proportion of clinically significant prostate cancer.

INTRODUCTION AND OBJECTIVES:Active surveillance (AS) has become an accepted management strategy for very low risk, low risk, and select cases of favorable intermediate risk localized prostate cance...

At most centers strict age criteria are lacking for eligibility for active surveillance of prostate cancer. Younger men are often counseled to undergo definitive treatment despite limited data on the outcomes of active surveillance in younger men. We compared clinical characteristics and outcomes in men who enrolled in active surveillance at age less than 60 vs 60 years old or older.We retrospectively reviewed the records of 2 institutional cohorts of a total of 2,084 men in whom prostate cancer was managed by active surveillance between 1995 and 2016. We compared outcomes in men who began active surveillance at age 60 vs 60 years or older using the Kaplan-Meier method and Cox proportional hazards regression.We identified 417 and 1,667 men who began active surveillance at younger than 60 and 60 years old or older, respectively, who met study inclusion criteria. At a median followup of 6.2 years we found no significant difference between men younger than 60 and 60 years old or older in the 5-year rates of biopsy progression-free survival (83% vs 83%), treatment-free survival (74% vs 71%), metastasis-free survival (99.7% vs 99.0%) or prostate cancer specific survival (100% vs 99.7%). Of the younger men 131 (31%) ultimately underwent treatment, including for pathological progression in 67% and prostate specific antigen progression in 18%. On multivariate analysis significant predictors of biopsy progression and progression to treatment among younger men were 20% or greater involvement of any core on diagnostic biopsy (HR 2.21, p = 0.003) and prostate specific antigen density 0.15 ng/ml/ml or greater (HR 1.93, p = 0.01).Active surveillance is a viable option in select men younger than 60 years with low volume, low risk prostate cancer. However, patients must be surveyed closely and understand the significant likelihood of ultimately requiring treatment.