The impact of non-structured PSA testing on prostate cancer-specific mortality on New Zealand Maori men.

OBJECTIVES: To assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Maori men in a New Zealand (NZ) population. PATIENTS AND METHODS: Maori men aged 40 years or older, without a history of PCa, with a PSA test between 2006 and 2018 were included. The cohort was divided into two groups; the "screened group" (ScG) consisting of men who had at least one PSA test every four years or less, and the "non-screened group" (non-SG). We measured the rate of cancer diagnoses and used competing risk analysis to assess survival. RESULTS: The study cohort included 63,939 Maori men, with 37,048 (58%) in the ScG. PCa was more frequently diagnosed in the ScG (3.7% vs. 3.0%, P < 0.001). A higher proportion of high-grade cancers were found in the non-SG (32.7% vs. 25.6%, P = 0.001). The 10-year cancer-specific survival was significantly higher in the ScG (99.4% vs. 98.5%, P < 0.001). In a multivariable risk model, PSA testing frequency was an independent predictor of PCa mortality. (HR 2.43, [95% CI 1.97-3.01], P < 0.001). CONCLUSIONS: In a cohort of only Maori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Maori could improve cancer-specific survival among Maori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

The impact of the extent and location of positive surgical margins on the risk of biochemical recurrence following radical prostatectomy in men with Gleason 7 prostate cancers.

BACKGROUND: Positive surgical margins (PSM) after radical prostatectomy (RP) have been associated with increased risk of biochemical recurrence (BCR). This is heavily influenced by other clinicopathological factors. This study aims to assess the impact of the extent and location of PSM on BCR following RP for Gleason 7 carcinoma of the prostate (CaP). MATERIALS AND METHODS: All men treated with RP between 2008 and 2017 in our region for localized or locally advanced Gleason 7 CaP, were included. Clinical (age, year, preoperative prostate specific antigen) and pathological (prostate weight, positive or negative surgical margins, International Society of Urological Pathology [ISUP] grade, T stage) data were collected. PSM were subcategorised according to Extent into favourable (unifocal and <3 mm in length) or unfavourable (multifocal or ≥3 mm in length), and Location into apical only or others. The outcome was the risk of BCR which was calculated with univariable and multivariable regression models and reported as hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The cohort constituted of 1433 men. Majority had ISUP 2 (71.2%) or localized (62%) disease. Men with PSM (n = 506) were at greater risk of BCR when compared to those with negative margins (adjusted HR = 1.52, [CI: 1.14-2.04], p = .005). Similar observation was demonstrated for both PSM location subgroups. As for the PSM extent category, only men with unfavourable PSM demonstrated an increase in BCR risk over negative margin (adjusted HR = 1.67, [CI: 1.23-2.28], p = .001). CONCLUSIONS: Within this study settings, PSM were generally associated with increased BCR risk. This, however, was not demonstrated in favourable PSM extent cases. Observation rather than active treatment in these men should be considered.

Ethnic and socio-economic disparities in prostate cancer screening: lessons from New Zealand.

OBJECTIVES: To investigate the presence of ethnic and socio-economic disparities in prostate cancer (PCa) screening and identify its impact on cancer outcomes. MATERIALS AND METHODS: From January 2008 to December 2017, all men in the Northern region of New Zealand who had a prostate-specific antigen (PSA) test performed in the community were identified from the electronic laboratory reports database. Asymptomatic men, with no known diagnosis of PCa, were included. Variables collected were age, ethnicity, social deprivation, medical therapy, PSA test information and cancer data. Disparities were investigated by comparing the frequency of PSA testing, proportions of men screened, and rates of cancer detection, between Maori (indigenous) and non-Maori ethnic groups. RESULTS: The study cohort included 248 491 men, who each received approximately 3.45 PSA tests over the 10-year study period. Maori men were less likely to be tested compared to non-Maori men (25.4% vs 46.1% of the total aged-matched region population; P < 0.001). Moreover, they received less frequent PSA testing irrespective of their deprivation status (mean difference of 0.97 PSA tests per person; P < 0.001). The higher testing frequency in non-Maori men was associated with increased PCa diagnosis rates. Nevertheless, cancers detected in Maori men were 73% more likely to be of high grade (Gleason 8 or above), compared to those in non-Maori men. CONCLUSION: There were significant ethnic disparities in PCa screening rates in the Northern region of New Zealand. Maori men, regardless of other demographic factors, were disproportionately affected. The difference in the rates of screening by ethnicity had influenced the incidence and clinical significance of the diagnosed cancers.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Age-adjusted reference values for prostate-specific antigen in a multi-ethnic population.

OBJECTIVE: To establish age-adjusted reference values for prostate-specific antigen in an ethnically diverse population. METHODS: Between 2009 and 2017, data were collected from all men aged 40-79 years, who had a prostate-specific antigen test in the northern region of New Zealand, where the prostate-specific antigen testing service is provided by a single community laboratory and using the same assay analyzer. Men known to have prostate cancer, who developed prostate cancer during the study period, who were treated with finasteride, or who had prostate-specific antigen levels above 20 ng/mL were excluded. Age-adjusted prostate-specific antigen reference values were calculated for each of the main ethnic groups in the country including: Maori (indigenous), Pacific, Asian and European. For every 5-year age interval, the 95th percentile of the log prostate-specific antigen distribution was used to define the upper limit of normal. RESULTS: The study cohort included 215 132 apparently healthy men, with a median age and prostate-specific antigen concentration of 59 years and 0.9 ng/mL, respectively. Prostate-specific antigen levels for the entire cohort increased with age (Pearson correlation = 0.362, P < 0.001). This relationship was most prominent in Pacific men. Similarly, the upper reference limit for the entire cohort increased with age, from 1.60 ng/mL for men aged 40-44 years to 7.61 ng/mL for those aged 75-79 years. Significant ethnic differences were present within each interval, which was most apparent in the older age groups. CONCLUSION: Ethnic differences in age-adjusted prostate-specific antigen reference values are present in New Zealand. These need to be considered when prostate-specific antigen results are being interpreted in clinical practice.

Predictors of surgical intervention following initial surveillance for acute ureteric colic.

PURPOSE: To identify clinical and stone-related factors predicting the need for surgical intervention in patients who were clinically considered appropriate for non-surgical intervention. PATIENTS AND METHODS: We conducted a retrospective review of a contemporary cohort of patients who were selected for surveillance following presentation with acute ureteric colic. Data on patient demographic and stone variables, inpatient management and long-term outcomes were evaluated. Multivariate logistic regression was used to generate a nomogram predicting need for surgical intervention. The accuracy of the nomogram was subsequently validated with an independent cohort of patients presenting with ureteric colic. RESULTS: Of 870 study eligible patients presenting with acute ureteric colic, 527 were initially treated non-surgically and included in the analysis. 113 of these eventually required surgical intervention. Median time from first presentation to acute surgery was 11 (IQR 4-82) days. In our final MVA analysis, duration of symptoms more than 3 days, not receiving alpha-blockers, positive history of previous renal calculi and stone location, burden and density were independent predictors of need for surgical intervention. Patients who required opioid analgesia were more likely to have surgical intervention; however, this did not reach statistical significance. The area under the curve (AUC) of the final model was 0.802. The nomogram was validated with a cohort of 210 consecutive colic patients with AUC of 0.833 (SE 0.041, p < 0.001). CONCLUSIONS: We have identified independent predictors of the need for surgical intervention during an episode of renal colic and formulated a nomogram. Combined with the diligent use of acute ureteroscopy at our centre, this nomogram may have clinical utility when making decisions regarding treatment options with potential healthcare cost savings.

Cytoreductive Nephrectomy for Renal Cell Carcinoma with Venous Tumor Thrombus.

PURPOSE: Careful selection is critical to identify those with metastatic renal cell carcinoma who are most likely to benefit from cytoreductive nephrectomy. Surgery in patients who have metastatic renal cell carcinoma with tumor thrombus is complex and may not benefit some patients with poor overall survival. We evaluated whether preoperative variables or risk stratification systems could predict overall survival following cytoreductive nephrectomy. MATERIALS AND METHODS: Prognostic factors for overall survival after surgery were evaluated in patients who had metastatic renal cell carcinoma with venous tumor thrombus at 5 institutions from 2000 to 2014. Prognostic variables, including metastatic renal cell carcinoma risk models, were evaluated for associations with overall survival. Multivariable analysis was used to determine independent associations of preoperative variables with overall survival. RESULTS: A total of 427 patients with metastatic renal cell carcinoma were identified with tumor thrombus. Patients with inferior vena cava thrombus above the diaphragm had shorter median overall survival vs those with renal vein only thrombus (9.2 months, IQR 4.2-30.8, vs 21.7, IQR 7.7-42.8, p = 0.0165). Individual risk factors from prognostic models were evaluated among other preoperative characteristics for associations with overall survival in 122 patients (32%) who died within 270 days of surgery. Independent predictors of overall survival included lactate dehydrogenase greater than the upper limit of normal (p = 0.003), systemic symptoms (p = 0.003), inferior vena cava thrombus above the diaphragm (p = 0.02) and sarcomatoid features (p = 0.005). CONCLUSIONS: Poor overall survival following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma with tumor thrombus is associated with inferior vena cava thrombus above the diaphragm, poor risk group, systemic symptoms or sarcomatoid dedifferentiation. Patients with expected poor overall survival should be considered for preoperative systemic therapy clinical trials.

Surgical control and margin status after robotic and open cystectomy in high-risk cases: Caution or equivalence?

PURPOSE: The benefits of robotic-assisted radical cystectomy (RARC) are unclear, especially in patients with high-risk disease (pT3/T4). We evaluated pathological and postoperative outcomes of RARC versus open radical cystectomy (ORC) in these patients. METHODS: We identified bladder cancer patients treated with RARC or ORC from January 2010-August 2014. Clinicodemographic factors were examined for potential confounding. Our primary outcome of interest was positive soft-tissue surgical margins (STSMs). Secondary outcomes included post-operative complications and length of stay (LOS). We used logistic regression to define the association between clinical factors with outcomes of interest, focusing on patients with locally advanced disease. RESULTS: We identified 472 patients treated with ORC (407, 86.2 %) or RARC (65, 13.8 %) of which 215 (45.6 %) were high-risk cases based on advanced pathologic stage (pT3/4). RARC patients were more commonly men (96.9 vs. 73.2 %, p < 0.01), had better performance status (ECOG 0, 78.5 vs. 59.7 %, p = 0.031), and received less neoadjuvant chemotherapy (21.5 vs. 39.3 %, p = 0.006). Total (52.3 vs. 59.7 %, p = 0.26) and high-grade complication rates (13.8 vs. 19.7 %, p = 0.27) were similar, but median LOS was shorter after RARC (6 vs. 7 days, p < 0.01). On multivariate analysis, prior pelvic radiation (OR: 4.78, 95 % CI: 2.16-10.57), and advanced tumor stage (OR: 3.06, 95 % CI: 1.56-6.03) were independently associated with positive STSMs in high-risk patients but robotic surgical approach was not (OR: 0.81, 95 % CI: 0.29-2.30; p = 0.69). CONCLUSION: RARC had similar short-term postoperative outcomes compared to ORC and did not compromise oncological control in patients with extravesical disease.

Dose dense MVAC prior to radical cystectomy: a real-world experience.

PURPOSE: Our primary endpoint was to assess pathological response rate (pT0N0 and ≤pT1N0) for patients with BCa treated with the accelerated or dose dense MVAC (ddMVAC) chemotherapy followed by radical cystectomy (RC) in this real-word multi-institutional cohort. MATERIALS AND METHODS: We retrospectively reviewed records of patients with urothelial cancer who underwent ddMVAC and RC at seven contributing institutions from 2000 to 2015. Patients with cT2-4a, M0 BCa were included. Presence of cT3-4 disease, hydronephrosis, lymphovascular invasion and/or existence of sarcomatoid, or micropapillary features on the initial transurethral resection of bladder tumor specimen was defined as high-risk disease. Logistic regression models for prediction of pT0N0 and ≤pT1N0 were generated for the entire cohort as well as for the cN0 subgroup. The multivariable Cox proportional hazards regression model for survival using post RC data was used to assess hazard ratios (HRs) for the variables of interest. RESULTS: A total of 345 patients received ddMVAC chemotherapy during the study period; 85% had high-risk features. The median number of chemotherapy cycles was 4 (IQR 4-4); >90% of patients completed all scheduled cycles. The observed rates of pT0N0 and ≤pT1N0 were 30.4 and 49.3%, respectively, among cN0 patients. On the multivariable regression model, the presence of more than one clinical high-risk element was associated with 70% [OR 0.30 95% CI (0.10-0.86); p = 0.02] reduction in the odds of achieving partial pathological response. CONCLUSIONS: A complete response (pT0N0) was observed in one-third of patients after neoadjuvant ddMVAC therapy, and a partial response (≤pT1N0) was observed in nearly half of the cases in this real-world experience with this regimen. To our knowledge, this represents the largest experience outside clinical trial settings.

Bilateral benign renal oncocytomas and the role of renal biopsy: single institution review.

BACKGROUND: The goal was to assess the natural history and management of patients with pathologically proven bilateral (synchronous) RO after undergoing initial partial nephrectomy (PN). METHODS: All patients underwent either robotic/laparoscopic or open PN by two experienced genitourinary oncologists from 2005-2013. Final pathology was determined by surgical excision, CT-guided percutaneous core biopsy (CT-biopsy) or fine needle aspiration (FNA). Patient demographics, tumor characteristics (pathologic data, location, size) type of surgery, pre/post estimated glomerular filtration rate (eGFR) and surgical complications were recorded. RESULTS: Twelve patients were identified with bilateral RO. Median age at the time of surgery was 68 years (46-77) (Table 1). The median size of the largest tumor(s) resected was 2.75 cm (1.5-5.5 cm) and second largest tumor(s) was 1.75 cm (1.0-4.0 cm). Four patients underwent bilateral staged PN and one patient underwent simultaneous bilateral PN (horseshoe kidney). Two patients underwent RFA at the time of biopsy of the contralateral mass after PN. Five patients underwent CT-bx/FNA (5/5) of the contralateral mass followed by active surveillance. Mean follow up was 34 months. There was no significant change in median creatinine pre- and post-operatively. One patient was lost to follow up and one patient died of unknown causes 5 years post-operatively. eGFR decreased an average of 16.96% post-operatively, including a single patient whose eGFR increased by 7.8% after surgery and a single patient whose eGFR did not change (Table 2). CONCLUSIONS: Patients with bilateral renal masses and pathologically proven RO can be safely managed with active surveillance after biopsy confirmation of the contralateral mass.

Final Pathological Stage after Neoadjuvant Chemotherapy and Radical Cystectomy for Bladder Cancer-Does pT0 Predict Better Survival than pTa/Tis/T1?

PURPOSE: We assessed survival dependent on pathological response after neoadjuvant chemotherapy in a large multicenter patient cohort, with a particular focus on the difference between the absence of residual cancer (pT0) and the presence of only nonmuscle invasive residual cancer (pTa, pTis, pT1). MATERIALS AND METHODS: We retrospectively reviewed records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent radical cystectomy at 19 contributing institutions from 2000 to 2013. Patients with cT2-4aN0M0 and eventual pN0 disease were selected for this analysis. Estimated overall survival was compared between patients with pT0 and pTa/Tis/T1 disease. A multivariable Cox proportional hazards regression model for overall survival was generated to evaluate hazard ratios for variables of interest. RESULTS: Of 1,543 patients treated with neoadjuvant chemotherapy and radical cystectomy during the study period 257 had pT0N0 and 207 had pTa/Tis/T1N0 disease. The Kaplan-Meier mean estimates of overall survival for pT0 and pTa/Tis/T1 cases were 186.7 months (95% CI 145.9-227.6, median 241.1) and 138 months (95% CI 118.2-157.8, median 187.4), respectively (p=0.58). In the Cox proportional hazards regression model for overall survival pTa/Tis/T1N0 status (HR 0.36, 95% CI 0.23-0.67) and pT0N0 status (HR 0.28, 95% CI 0.17-0.47) compared to pT2N0 pathology, positive surgical margin (HR 1.75, 95% CI 1.07-2.86), and receiving a methotrexate, vinblastine, doxorubicin and cisplatin regimen compared to an "other" regimen (HR 0.45, 95% CI 0.27-0.76) were predictors of overall survival. CONCLUSIONS: pTa/Tis/T1N0 and pT0N0 stage on the final cystectomy specimen are strong predictors of survival in patients treated with neoadjuvant chemotherapy and radical cystectomy. We did not discern a statistically significant difference in overall survival when comparing these 2 end points.

Preoperative Patient Reported Mental Health is Associated with High Grade Complications after Radical Cystectomy.

PURPOSE: Psychological distress has been associated with an impaired immune response and poor wound healing. We hypothesized that preoperative patient reported mental health would be associated with high grade 30-day complications after radical cystectomy. MATERIALS AND METHODS: We retrospectively identified patients who underwent radical cystectomy for bladder cancer who completed Short Form 12 (SF-12) surveys for self-assessment of health status less than 6 months before surgery. Median physical and mental composite scores were calculated. An expert model including known predictors of postoperative high grade complications was developed, and SF-12 physical composite score and mental composite score were added to determine their association with this end point. RESULTS: From January 2010 to August 2014, 472 patients underwent radical cystectomy for bladder cancer, of whom 274 (58.1%) completed preoperative SF-12 questionnaires. Responders were more likely to be white (p=0.024), have higher preoperative albumin (p=0.037), receive neoadjuvant chemotherapy (p=0.002), have pT3/T4 disease (p=0.044) and have positive soft tissue surgical margins (p=0.006). Median SF-12 physical composite score was 43.1 (IQR 33.0-51.5) and mental composite score was 48.5 (IQR 39.5-54.7) in responders. Overall 46 (16.8%) responders experienced a high grade 30-day complication. Patients with a high grade complication had a lower preoperative median SF-12 mental composite score (44.8 vs 49.8, p=0.004) but no difference in physical composite score (39.2 vs 43.8, p=0.06). SF-12 mental composite score was also a significant predictive variable when added to our expert model (p=0.01). CONCLUSIONS: Preoperative patient reported mental health was independently associated with high grade complications after radical cystectomy. Therefore, patient self-assessment of health status before surgery through validated questionnaires may provide additional information useful in predicting short-term postoperative outcomes.

A Multi-Institutional Analysis of Outcomes of Patients with Clinically Node Positive Urothelial Bladder Cancer Treated with Induction Chemotherapy and Radical Cystectomy.

PURPOSE: Selected patients with bladder cancer with pelvic lymphadenopathy (cN1-3) are treated with induction chemotherapy followed by radical cystectomy. However, the data on clinical outcomes in these patients are limited. In this study we assess pathological and survival outcomes in patients with cN1-3 disease treated with induction chemotherapy and radical cystectomy. MATERIALS AND METHODS: Data were collected on patients from 19 North American and European centers with cT1-4aN1-N3 urothelial carcinoma who received chemotherapy followed by radical cystectomy between 2000 and 2013. The primary end points were pathological complete (pT0N0) and partial (pT1N0 or less) response rates, with overall survival as a secondary end point. Logistic regression and Cox proportional hazard ratios were used for multivariate analysis of factors predicting these outcomes. RESULTS: The total of 304 patients had clinical evidence of lymph node involvement (cN1-N3). Methotrexate/vinblastine/doxorubicin/cisplatin was used in 128 (42%), gemcitabine/cisplatin in 132 (43%) and other regimens in 44 (15%) patients. The pN0 rate was 48% (cN1-56%, cN2-39%, cN3-39%, p=0.03). The complete and partial pathological response rates for the entire cohort were 14.5% and 27%, respectively. The estimated median overall survival time for the cohort was 22 months (IQR 8.0, 54). On Cox regression analysis overall survival was associated with pN0, negative surgical margins, removal of 15 or more pelvic nodes and cisplatin therapy. CONCLUSIONS: Complete pathological nodal response can be achieved in a proportion of patients with cN1-3 disease receiving induction chemotherapy. The best survival outcomes are observed in male patients on cisplatin regimens with subsequent negative radical cystectomy margins and complete nodal response (pN0) with excision of 15 or more pelvic nodes.

Extent of pelvic lymph node dissection in penile cancer may impact survival.

INTRODUCTION: Current guidelines on management of penile carcinoma (PC) recommend ipsilateral pelvic lymph node dissection (PLND) in patients with inguinal lymph node metastasis (LNM) who meet specific criteria. The aim of this article was to assess outcomes in patients treated with bilateral PLND in the presence of unilateral metastatic pelvic nodes. METHODS: After IRB approval, four international centers contributed to this study. Men with PC and unilateral inguinal LNM and pelvic node metastases were retrospectively analyzed. Estimates of overall survival (OS) and cancer-specific survival were provided by the Kaplan-Meier method. Comparisons between subgroups were made using the log-rank test, and Cox regression analysis was used to adjust comparisons for covariates of interest. RESULTS: From 1978 to 2012, fifty-one men with unilateral inguinal LNM and positive pelvic nodes on PLND were identified. Thirty-eight (75 %) had ipsilateral and 13 (25 %) had bilateral PLND. Except the extent of the PLND, patients were comparable with respect to disease and therapeutic interventions. The Kaplan-Meier estimated median OS was significantly longer in the bilateral PLND patients (21.7 vs. 13.1, p = 0.051). On Cox regression analysis, bilateral PLND [HR 0.25, (95 % CI 0.10-0.64)], multiple pelvic node involvement [HR 2.12 (95 % CI 1.02-4.43)], neoadjuvant chemotherapy [HR 0.01, (95 % CI 0.02-0.44)] and adjuvant therapies [HR 0.16, (95 % CI 0.06-0.45)] (compared to no additional therapy) were independent predictors of OS. CONCLUSIONS: Men with PC and pelvic node metastases may benefit from a bilateral PLND. This hypothesis requires further confirmation.

Clinical role of additional adjuvant chemotherapy in patients with locally advanced urothelial carcinoma following neoadjuvant chemotherapy and cystectomy.

PURPOSE: Neoadjuvant chemotherapy (NAC) can downstage invasive bladder cancers prior to radical cystectomy (RC) and improve overall survival. However, the optimal management in patients with persistent non-organ confined disease (pT3-T4 and/or pN+) following RC has not been completely defined. The aim of this study was to describe outcomes associated with the use of adjuvant chemotherapy (AC) in patients with residual non-organ confined cancer at RC following NAC. MATERIALS AND METHODS: Using data from a high-volume referral institution, pT3-T4 and/or pN+ patients who received NAC and then also RC were identified. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed with Kaplan-Meier analysis. RESULTS: From 2001 to 2013, 161 patients received NAC and then RC. Eighty-eight pT3-T4 and/or pN+ patients were identified. Twenty-nine (33 %) received AC. Adjuvant chemotherapy in the majority of patients was carboplatin-based (16), followed by cisplatin (8) and other, mainly taxane-containing regimens (5). The median RFS was 17.5 months in the AC and 13.7 months in the non-AC group (p = 0.78). AC remained an insignificant predictor for RFS after adjusting for pT, pN and margin status (HR 0.89, 95 % CI 0.48-1.68]). CSS was 23 and 22 months (p = 0.65) and remained insignificant after adjusting for pathologic confounders. CONCLUSIONS: In our current study population, adjuvant conventional cytotoxic chemotherapy was not associated with significant improvements in RFS or CSS. The choice of AC regimens, and incorporation of newer treatments, may be the key for improving outcomes in this high-risk patient group.

Clinical and therapeutic factors associated with adverse pathological outcomes in clinically node-negative patients treated with neoadjuvant cisplatin-based chemotherapy and radical cystectomy.

PURPOSE: Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4aN0M0 UC who received three or four cycles of NAC followed by RC were selected. Logistic regression was used to predict pN+,

Disparities in Penile Cancer.

BACKGROUND: Although penile cancer is a rare malignancy in developed nations, racial and socioeconomic differences exist in the incidence of the disease and its associated survival-related outcomes. METHODS: A search of the literature was performed for research published between the years 1990 and 2015. Case reports and non-English-language articles were excluded, instead focusing specifically on large, population-based studies. RESULTS: The incidence of penile cancer is higher in Hispanic and African American men compared with whites and Asians. Men with penile cancer also appear to have a distinct epidemiological profile, including lower educational and income levels, a history of multiple sexual partners and sexually transmitted infections, and lack of circumcision with the presence of phimosis. African American men presented at a younger age with a higher stage of disease and worse survival rates when compared with white men. Rates of cancer-specific mortality increased with age, single marital status, and among those living in regions of lower socioeconomic status. CONCLUSIONS: An understanding of sociodemographical differences in the incidence and survival rates of patients with penile cancer can help advance health care policy changes designed to improve access and minimize disparities in cancer care for all men alike.

Peritoneal Cytokine Levels Can Predict Anastomotic Leak on the First Postoperative Day.

BACKGROUND: Accumulating evidence suggests that peritoneal cytokine concentrations may predict anastomotic leak after colorectal surgery, but previous studies have been underpowered. OBJECTIVE: We aimed to test this hypothesis by using a larger prospectively collected data set. DESIGN: This study is an analysis of prospectively collected data. SETTINGS: This study was conducted at 3 public hospitals in Auckland, New Zealand. PATIENTS: Patients undergoing colorectal surgery recruited as part of 3 previous randomized controlled trials were included. MAIN OUTCOME MEASURES: Data on peritoneal and plasma levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α on day 1 after colorectal surgery were reanalyzed to evaluate their predictive value for clinically important anastomotic leak. Area under receiver operating characteristic curve analysis was performed. RESULTS: A total of 206 patients with complete cytokine data were included. The overall anastomotic leak rate was 8.3%. Concentration levels of peritoneal interleukin-6 and interleukin-10 on day 1 after colorectal surgery were predictive of anastomotic leak (area under receiver operating characteristic curve, 0.72 and 0.74; p = 0.006 and 0.004). Plasma cytokine levels of interleukin-6 were higher on day 1 after colorectal surgery in patients who had an anastomotic leak, but this was a poor predictor of anastomotic leak. Levels of other peritoneal and plasma cytokines were not predictive. LIMITATIONS: The study was not powered a priori for anastomotic leak prediction. Although the current data do suggest that peritoneal levels of interleukin-6 and interleukin-10 are predictive of leak, the discriminative value in clinical practice remains unclear. CONCLUSIONS: Peritoneal levels of interleukin-6 and interleukin-10 on day 1 after colorectal surgery can predict clinically important anastomotic leak.