Impact of PI3K-AKT-mTOR Signaling Pathway Up-regulation on Prognosis of Penile Squamous-Cell Carcinoma: Results From a Tissue Microarray Study and Review of the Literature.

PURPOSE: To assess the prognostic value of PI3K-AKT-mTOR signaling pathway up-regulation in a contemporary cohort of penile squamous-cell carcinoma (PSCC) patients. PATIENTS AND METHODS: Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence. RESULTS: HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47-10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55-24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42-20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02-22.48; P = .002). CONCLUSION: PI3K-AKT-mTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation.

Trends in Insurance Status during Initial Presentation of Testicular Carcinoma: Examining Health Outcomes and Implications of Health Reform for Young Adults in the United States.

INTRODUCTION: We evaluated trends in insurance status, and assessed socioeconomic factors associated with clinically metastatic testicular cancer presentation and potential barriers to treatment in the United States. METHODS: The National Cancer Database was queried for patients with testicular germ cell tumors diagnosed from 2004 to 2014. Temporal trends and forecast of insurance status were examined in the years before and after the ACA (Affordable Care Act) was enacted. Multivariable logistic regression was used to assess predictors of clinically metastatic presentation. RESULTS: A total of 58,348 patients were identified with 37.95% presenting with clinically metastatic disease. The uninsured rate remained relatively unchanged during the years before and after the ACA was enacted (11.7% vs 11.9%, respectively). Predictors for clinically metastatic presentation were Medicaid (OR 2.12, 95% CI 1.80-2.50), Medicare (OR 1.35, 95% CI 1.13-1.60) and uninsured status (OR 1.41, 95% CI 1.22-1.64) compared to privately insured patients. A forecast model revealed no significant changes in the uninsured rate (11.58% to 11.60%) for 2015 through 2017. CONCLUSIONS: Socioeconomic disparities continue to be barriers for young adults presenting with testicular cancer in the United States. Longer prospective followup will be required to assess the impact of payer status with the reportedly increased health coverage fostered by the ACA.

Implications of Programmed Death Ligand-1 Positivity in Non-Clear Cell Renal Cell Carcinoma.

The purpose of this study was to assess the prognostic value of programmed death ligand-1 (PD-L1) positivity in a non-clear cell renal cell carcinoma (non-ccRCC) cohort. PD-L1 expression was evaluated by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) specimens from 45 non-ccRCC patients with available tissue. PD-L1 positivity was defined as ≥1% of staining. Histopathological characteristics and oncological outcomes were correlated to PD-L1 expression. Cancer-specific survival (CSS) and recurrence-free survival (RFS) stratified by PD-L1 status were estimated using the Kaplan-Meier method. Median age was 58 years and median follow-up was 40 months. Non-ccRCC subtypes included sarcomatoid (n = 9), rhabdoid (n = 6), medullary (n = 2), Xp11.2 translocation (n = 2), collecting duct (n = 1), papillary type I (n = 11), and papillary type II (n = 14). PD-L1 positivity was noted in nine (20%) patients. PD-L1 positivity was significantly associated with higher Fuhrman nuclear grade (P = 0.048) and perineural invasion (P = 0.043). Five-year CSS was 73.2 and 83% for PD-L1 positive and negative tumors, respectively (P = 0.47). Five-year RFS was 55.6 and 61.5% for PD-L1 positive and negative tumors, respectively (P = 0.58). PD-L1 was expressed in a fifth of non-ccRCC cases and was associated with adverse histopathologic features. Expression of biomarkers such PD-L1 may help better risk-stratify non-ccRCC patients to guide treatment decisions and follow-up strategies.

National Trends and Predictors of Organ-sparing for Invasive Penile Tumors: Expanding the Therapeutic Window.

INTRODUCTION: The purpose of this study was to analyze contemporary trends and predictors in the use of organ-sparing treatment (OST) for low-stage invasive penile tumors as well as to ascertain its impact on overall mortality (OM) in those with high-risk (pT2) disease. PATIENTS AND METHODS: The National Cancer Data Base was queried for patients with clinically nonmetastatic penile cancer and available pathologic tumor (pT) and treatment data from 1998 to 2012. Independent predictors for performance of OST were analyzed. Multivariable Cox proportional hazard regression was used to identify factors of OM in a subset of patients with pT2 disease. RESULTS: A total of 4231 patients with ≤ pT2cN0cM0 primary penile cancer were identified over a median follow-up of 39.6 months. Approximately 49% of patients received OST over the study period (P = .009). Older age, Hispanic ethnicity, urban counties, academic facilities, and pT2 disease were negative predictors for OST (all P < .05), whereas grade and years of diagnosis where associated with increased performance (P < .01). In subgroup analysis of pT2 patients, older age, black race, comorbidity, node status, and grade were associated with higher OM (all P < .05). When compared with radical penectomy, partial penectomy was associated with decreased OM (hazard ratio, 0.67; 95% confidence interval, 0.52-0.87; P = .002), whereas organ-sparing did not affect survival (hazard ratio, 0.83; 95% confidence interval, 0.52-1.31; P = .419) in these patients. CONCLUSION: Ethnic and socioeconomic differences exist in the local management of penile tumors. No impact on OM was observed for those with high-risk cases treated with organ-sparing at intermediate follow-up. More studies are needed to evaluate oncologic efficacy of organ-sparing in carefully selected invasive penile tumors.

Surgical management of penile carcinoma in situ: results from an international collaborative study and review of the literature.

OBJECTIVES: To evaluate recurrence after penile-sparing surgery (PSS) in the management of carcinoma in situ (CIS) of the penis in a large multicentre cohort of patients. PATIENTS AND METHODS: We identified consecutive patients from five major academic centres, treated between June 1986 and November 2014, who underwent PSS for pathologically proven penile CIS. The primary outcome was local recurrence-free survival (RFS), which was estimated using the Kaplan-Meier method. RESULTS: A total of 205 patients were identified. Treatment methods included circumcision, glansectomy, wide local excision, laser therapy and total glans resurfacing. Over a median (interquartile range [IQR]) follow-up of 40 (26-65.6) months, there were 48 local recurrences, with 45.8% occurring in the first year and 81.3% occurring by year 5. The majority of recurrences were observed in the laser group (58.3%). The median (IQR) time to local recurrence was 15.9 (5.66-26.14) months. The 1- 2- and 5-year RFS rates were 88.4, 85.6 and 75%, respectively, and the median (IQR) RFS time was 106.5 (80.2-132.2) months. CONCLUSIONS: Among patients with penile CIS selected for surgical management, durable responses at intermediate- to long-term follow-up were noted. For those with glandular CIS, glans resurfacing offered the best outcomes.

Postchemotherapy lymph node dissection for isolated retroperitoneal nodal recurrences for penile cancer: Is cure possible in highly selected cases?

Outcomes for advanced penile carcinoma remain poor with limited options for curative treatment. Nodal recurrences represent worse prognosis and are typically treated with a combination of radiation, chemotherapy, or consolidative resection. Although the ideal management for recurrences remains unknown, there is some evidence supporting the role of chemotherapy followed by consolidative resection. Using a multimodal strategy, we describe the curative potential of postchemotherapy retroperitoneal lymph node dissection for penile cancer patients with isolated locoregional recurrences in the retroperitoneum.

Laser ablation as monotherapy for penile squamous cell carcinoma: A multi-center cohort analysis.

INTRODUCTION: Although the trend towards penile sparing therapy is increasing for penile squamous cell carcinoma, outcomes for laser ablation therapy have not been widely reported. We assessed the clinical outcomes of penile cancer patients treated with only laser ablation. MATERIALS AND METHODS: A retrospective review was performed on 161 patients across 5 multi-center tertiary referral centers from 1985 to 2015. All patients underwent penile sparing surgery with only laser ablation for squamous cell carcinoma of the penis. Laser ablation was performed with neodymium-doped yttrium aluminum garnet or carbon dioxide. Overall and recurrence-free survival was calculated using the Kaplan-Meier method and compared with the log rank test. RESULTS: A total of 161 patients underwent laser ablation for penile cancer. The median age was 62 (IQR: 52-71) years and median follow-up was 57.7 (IQR: 28-90) months. The majority of patients were pTa/Tis (59, 37%) or pT1a (62, 39%). Only 19 (12%) had a poorly differentiated grade. The 5-year recurrence-free survival was 46%. When stratified by stage, the 5-year local recurrence-free survival was pTa/Tis: 50%; pT1a: 41%; pT1b: 38%; and pT2: 52%. The inguinal/pelvic nodal recurrence was pTa/Tis: 2%; pT1a: 5%; pT1b: 18%; and pT2: 22%. There were no differences among stages with respect to recurrence-free survival (P = 0.98) or overall survival (P = 0.20). CONCLUSION: Laser ablation therapy is safe for appropriately selected patients with penile squamous cell carcinoma. Due to the increased risk of nodal recurrence, laser ablation coupled with diagnostic nodal staging is indicated for patients with pT1b or higher.

Penile Sparing Surgery for Penile Cancer: A Multicenter International Retrospective Cohort.

PURPOSE: We evaluated recurrence outcomes of penile sparing surgery in what is to our knowledge the largest multicenter cohort of patients to date. MATERIALS AND METHODS: We retrospectively identified patients treated with penile sparing surgery from May 1990 to July 2016 at 5 tertiary referral institutions. Treatments consisted of circumcision, wide local excision, laser therapy with or without local excision, partial or total glansectomy and glans resurfacing. The study primary end point was local recurrence-free survival, defined from initial treatment to time of local recurrence and estimated with the Kaplan-Meier method. RESULTS: After applying study exclusion criteria 1,188 patients were included in analysis. During the median followup of 43.0 months there were 252 local recurrences (21.2%), of which 99 (39.3%) developed in year 1. Median time to local recurrence was 16.3 months and the 5-year local recurrence-free survival incidence was 73.6%. When stratified by stage, the 5-year local recurrence-free survival rate was 75.0%, 71.4% and 75.9% in Ta/Tis, T1 and T2 cases, respectively (log rank p = 0.748). Of the recurrences 58.3% were treated with repeat organ sparing procedures and the secondary partial (total) penectomy rate was 19.0%. Only margin status was significantly associated with local recurrence on multivariate analysis (p = 0.001). Study limitations included the retrospective design and the heterogeneous clinical approach. CONCLUSIONS: Penile sparing surgery can provide excellent local control for superficial penile tumors as well as for appropriately selected invasive lesions. Strict followup in the early postoperative period is highly recommended.

Evaluating the accuracy of intraoperative frozen section during inguinal lymph node dissection in penile cancer.

INTRODUCTION: Inguinal lymph node dissection is an integral part in the management of invasive penile tumors with intraoperative assessment often aiding decision-making during dissection. In this study, we evaluate the diagnostic value of intraoperative frozen section (FS) and analyze clinicopathologic factors that affect its accuracy. MATERIAL AND METHODS: We, retrospectively, reviewed 84 patients with squamous cell carcinoma of the penis who underwent inguinal lymph node dissection at our institution. Intraoperative FS from the superficial inguinal nodes was available in 65 patients and compared with correspondent permanent sections (pathologic node staging [pN]). Sensitivity and specificity were calculated and factors associated with a false negative event were analyzed using logistic regression. RESULTS: The total positive node rate was 60% (39/65). Of 39 pN+ cases, 10 (25.6%) had false-negative FS, whereas the remaining 29 were concordant intraoperatively. Sensitivity and specificity were 0.74 and 1, respectively. On univariable analysis, higher body mass index was associated with a false negative event although there was no association with age, receipt of neoadjuvant therapy, or clinical node stage. CONCLUSION: Intraoperative FS is highly specific and moderately sensitive for the detection of positive superficial inguinal lymph nodes in penile cancer. Its use can help guide intraoperative surgical planning while limiting its reliance for patients with higher body mass index.

Glansectomy as Primary Management of Penile Squamous Cell Carcinoma: An International Study Collaboration.

OBJECTIVE: To analyze the recurrence and survival outcomes of glansectomy in patients with penile squamous cell carcinoma. MATERIALS AND METHODS: We performed a retrospective review of 410 patients across 5 international tertiary referral centers between 1999 and 2016. All patients had tumors involving the glans penis and underwent glansectomy as primary treatment. The Kaplan-Meier method and log-rank test were used to calculate survival and recurrence. Median follow-up was 42 months (interquartile range [IQR] 29-56). RESULTS: The median age was 64 years (IQR 53-72). Median tumor size was 2.2 cm (IQR 1.5-3.0). A total of 240 patients (58.5%) had pT2 disease, whereas only 43 patients (10.5%) had pT3 or pT4 disease. The majority of the cohort had poorly differentiated tumors (43.7%). Most recurrences were local at 7.6% (31 patients). Only 14 patients (3.4%) had regional recurrence and 9 patients (2.2%) had distant recurrence. When stratified by pathologic stage, tumors that were pT2 or higher were (P < .001) and were more likely to be poorly differentiated (P < .001). There were no differences in recurrence location among pathologic stages (P = .15). The 1-, 2-, and 5-year recurrence-free survival were 98%, 94%, and 78%, respectively. There were no differences in overall survival when stratified by stage (P = .67). CONCLUSION: Glansectomy is an oncologically safe treatment modality for squamous cell carcinoma of the glans in appropriately selected invasive tumors.

Adjuvant pelvic radiation is associated with improved survival and decreased disease recurrence in pelvic node-positive penile cancer after lymph node dissection: A multi-institutional study.

PURPOSE: Few studies have examined the role of radiation therapy in advanced penile squamous cell carcinoma. We sought to evaluate the association of adjuvant pelvic radiation with survival and recurrence for patients with penile cancer and positive pelvic lymph nodes (PLNs) after lymph node dissection. MATERIALS AND METHODS: Data were collected retrospectively across 4 international centers of patients with penile squamous cell carcinoma undergoing lymph node dissections from 1980 to 2013. Further, 92 patients with available adjuvant pelvic radiation status and positive PLNs were analyzed. Disease-specific survival (DSS) and recurrence were analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards model. RESULTS: 43% (n = 40) of patients received adjuvant pelvic radiation after a positive PLN dissection. Median follow-up was 9.3 months (interquartile range: 5.2-19.8). Patients receiving adjuvant pelvic radiation had a median DSS of 14.4 months vs. 8 months in the nonradiation group, respectively (P = 0.023). Patients without adjuvant pelvic radiation were associated with worse overall survival (hazard ratio [HR] = 1.7; 95% CI: 1.01-2.92; P = 0.04) and DSS (HR = 1.9; 95% CI: 1.09-3.36; P = 0.02) on multivariable analysis. Median time to recurrence was 7.7 months vs. 5.3 months in the radiation and nonradiation arm, respectively (P = 0.042). Patients without adjuvant pelvic radiation was also independently associated with higher overall recurrence on multivariable analysis (HR = 1.8; 95% CI: 1.06-3.12; P = 0.03). CONCLUSIONS: Adjuvant pelvic radiation is associated with improved survival and decreased recurrence in this population of patients with penile cancer with positive PLNs.

Delay to Inguinal Lymph Node Dissection Greater than 3 Months Predicts Poorer Recurrence-Free Survival for Patients with Penile Cancer.

PURPOSE: To our knowledge it is unknown whether concomitant inguinal lymph node dissection at the time of penectomy improves outcomes in patients with penile cancer. We analyzed predictors of regional recurrence as well as disease specific survival based on time of inguinal lymph node dissection. We also determined an optimal time to perform inguinal lymph node dissection. MATERIALS AND METHODS: We reviewed the records of 84 consecutive patients with available nodal pathology findings. Recurrence-free and disease specific survival was estimated using the Kaplan-Meier method. Optimal time to inguinal lymph node dissection was assessed by ROC curves and used for dichotomization. Cox proportional HRs were used to identify predictors of regional recurrence after inguinal lymph node dissection. RESULTS: A total of 47 (56%) and 37 patients (44%) presented with cN0 and cN+ disease, respectively, during a median followup of 21 months. A cutoff point of 3 months to perform inguinal lymph node dissection was used to dichotomize the cohort into early vs delayed groups. Early dissection in 51 men demonstrated 5-year recurrence-free survival of 77% vs 37.8% in 33 who underwent delayed dissection. Positive node disease (HR 23.2, 95% CI 2.98-181.2) and early inguinal lymph node dissection (HR 0.48, 95% CI 0.21-0.98) were predictors of regional recurrence. Five-year disease specific survival was 64.1% and 39.5% in the early and late dissection groups, respectively. CONCLUSIONS: Three months appears to be an optimal window for performing inguinal lymph node dissection. While prospective trials are needed to define the role of upfront groin dissection, our results may help delineate patterns of referral and timing of inguinal lymph node dissection in patients with penile cancer.

Management of Renal Masses in an Octogenarian Cohort: Is There a Right Approach?

BACKGROUND: We reviewed the outcomes for an octogenarian population to investigate whether active surveillance (AS) provides comparable survival to partial nephrectomy (PN) or radical nephrectomy (RN). PATIENTS AND METHODS: Data were collected from 115 octogenarian patients referred for management of renal masses at Moffitt Cancer Center from 2000 to 2013. Patients were treated with AS, PN, or RN. Univariable and multivariable Cox regression models measured the association between management modality and survival. Kaplan-Meier survival analysis was used to calculate survival, and log-rank tests were used to compare survival curves. RESULTS: The median age was 82 years (interquartile range, 81-85 years). The median follow-up period was 51 months (interquartile range, 23-81 months). Of the 115 patients, 31 (27%) underwent AS, 31 (27%) underwent PN, and 53 (46%) underwent RN. The patients who underwent RN had a larger mean tumor size at 5.5 cm, with 19 patients (36%) having stage ≥ pT3 (P < .001). We found no difference in overall survival or disease-specific survival among the 3 management strategies on univariable analysis (P = .39 and P = .1, respectively). On multivariable analysis for overall survival, only the Charlson comorbidity index was associated with worse survival (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P = .002). In a subgroup analysis of cT1a patients, we also found no difference in overall or disease-specific survival among the treatment arms on univariable analysis (P = .74 and P = .9, respectively). CONCLUSION: Active treatment with PN and RN might not provide a survival advantage compared with AS in the octogenarian population with a small renal mass. However, larger renal masses should undergo active treatment in appropriately selected patients.

Patterns of Regional Lymphadenectomy for Clinically Node-negative Patients With Penile Carcinoma: Analysis From the National Cancer Database From 1998 to 2012.

PURPOSE: Evidence supports upfront regional lymphadenectomy (rND) when primary penile tumors exhibit high-risk features and negative inguinal adenopathy (cN0). We sought to analyze trends in the utilization of early rND as well as assess factors associated with its use and survival outcomes using a nationwide cancer registry database. PATIENT AND METHODS: The National Cancer Database was queried for patients with clinically nonmetastatic penile carcinoma and available nodal status who underwent rND from 1998 to 2012. Temporal trends in the utilization of early rND for those with cN0 disease were analyzed, and a multivariable logistic regression model was used to identify predictors for receiving rND. Survival analysis based on rND status was performed using the Kaplan-Meier method and Cox proportional hazard regression. RESULTS: From 1919 patients with available clinicopathologic variables, performance of early rND was documented in 377 (19.6%) patients with an increase in utilization over time (P = .001). The increase was driven by academic and comprehensive cancer programs compared with community programs (P < .001). Positive predictors were treatment facility, clinical tumor stage, and grade (all P < .05). African American patients (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33-0.86; P = .01) and those aged > 75 years (OR, 0.42; 95% CI, 0.26-0.68; P < .001) were significantly less likely to receive rND. Early rND was associated with improved overall survival (hazard ratio [HR], 0.67; 95% CI, 0.52-0.87; P = .003). CONCLUSION: There was increased use of early lymphadenectomy for patients with cN0 penile cancer driven by comprehensive and academic cancer programs. The study demonstrated demographic and socioeconomic differences that can help identify barriers to care for patients with penile cancer in the United States.

Does Implementing an Enhanced Recovery After Surgery Protocol Increase Hospital Charges? Comparisons From a Radical Cystectomy Program at a Specialty Cancer Center.

OBJECTIVE: To compare perioperative charges induced at the initial phase of a standardized enhanced recovery after surgery (ERAS) program from a tertiary referral center. METHODS: A multidisciplinary ERAS protocol was implemented in our department on July 2015. During the subsequent year, all patients were treated according to this protocol (ERAS group). The patients were compared in terms of real in-hospital charges per surgical episode with a control group consisting of consecutive patients before the start of ERAS. Individual charges were analyzed per sample population and compared with the Wilcoxon rank-sum test or t test. Additionally, cost variances for each group were evaluated. RESULTS: A total of 257 consecutive patients were evaluated of which the last 112 were ERAS patients. The median length of stay for each group was 6 days (P = .748). ERAS patients incurred higher medication charges ($1939 vs $1729, P = .036). Control patients incurred higher supplies ($861 vs $692), treatment ($90 vs $72), and miscellaneous charges ($537 vs $388) (all, P < .001). The median total charges per patient were $59,539 for the control group and $60,655 for the ERAS group (P = .175). ERAS adoption significantly reduced variance in billed charges (P < .001). CONCLUSION: ERAS implementation did not significantly increase expenditure for cystectomy patients. ERAS showed decreased variance in charges likely due to standardization of care while eliciting savings in supplies, treatment, and miscellaneous costs.

Perioperative Transfusion of Leukocyte-depleted Blood Products in Contemporary Radical Cystectomy Cohort Does Not Adversely Impact Short-term Survival.

OBJECTIVE: To evaluate the effect of leukoreduced-only perioperative blood transfusion (PBT) and corresponding survival outcomes in a radical cystectomy cohort of patients. MATERIALS AND METHODS: We analyzed data from 1026 patients who underwent radical cystectomy at our institution. PBT was defined as transfusion in the intraoperative or within the postoperative hospitalization period. Multivariable analyses using Cox proportional hazards were performed to measure the association between PBT, patient variables, and 3 primary end points: recurrence-free survival, disease-specific survival, and overall survival. Kaplan-Meier curves estimated survival times and were compared with log-rank test. RESULTS: Overall, of a total of 1026 patients, 341 (33.2%) received leukoreduced PBT. The median follow-up was 27.5 months. Transfused patients were more likely to be female, had higher estimated blood loss, lower preoperative hemoglobin, were more likely to have received neoadjuvant chemotherapy, or had undergone a continent urinary diversion. Higher pathologic tumor and nodal stage were observed more frequently in patients who received PBT. On multivariable analysis, PBT was not associated with worse recurrence-free survival, disease-specific survival, and overall survival (all P > .05). Kaplan-Meier curves did not show any significant differences (all P > .05) between the transfused and nontransfused groups. In addition, no differences were found in regard to timing of transfusion, that is, intraoperative vs postoperative, in distinct analysis. CONCLUSION: No significant association was found between leukoreduced PBT and worse survival outcomes at short-term follow-up in a contemporary cohort of cystectomy patients. Prospective long-term follow-up is warranted.

Management of carcinoma in situ of the bladder: best practice and recent developments.

Management of carcinoma in situ of the bladder remains a complex and challenging endeavor due to its high rate of recurrence and progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Intravesical bacillus Calmette-Guérin is the standard first-line treatment given its superiority to other agents. However, high rates of bacillus Calmette-Guérin failure highlight the need for additional therapies. Radical cystectomy has traditional been the standard second-line therapy, but additional intravesical therapies may be more appealing for non-surgical candidates and patients refusing cystectomy. The subject of this review is the treatment strategies and available therapies currently available for carcinoma in situ of the bladder. It discusses alternative intravesical treatment options for patients whose condition has failed to respond to bacillus Calmette-Guérin therapy and who are unfit or unwilling to undergo cystectomy.

Lack of P16ink4a over expression in penile squamous cell carcinoma is associated with recurrence after lymph node dissection.

PURPOSE: There have been conflicting data in studies on the prognostic role of high risk human papillomavirus in penile squamous cell carcinoma. Using P16(ink4a) over expression as a surrogate marker for high risk human papillomavirus, we evaluated high risk human papillomavirus status with respect to various clinical features, including recurrence and overall survival, among others. MATERIALS AND METHODS: P16(ink4a) over expression was evaluated by immunohistochemistry for 119 consecutive patients with penile squamous cell carcinoma. Several variables were recorded including age, stage, histological grade, lymph node status, lymphovascular invasion, metastasis and recurrence. Median followup was 30 months. RESULTS: P16(ink4a) over expression was detected in 49.5% (59 of 119) of samples. There was no significant difference between P16(ink4a) negative and P16(ink4a) positive tumors in terms of stage (p = 0.518), histological grade (p = 0.225), lymphovascular invasion (p = 0.388), overall survival (p = 0.156) or lymph node metastasis (p = 0.748). P16(ink4a) negative tumors were more likely to recur overall (p = 0.04), especially if patients had positive lymph nodes at diagnosis (p = 0.002). CONCLUSIONS: These data suggest that P16(ink4a)/high risk human papillomavirus status is associated with recurrence, especially in patients with positive lymph nodes at diagnosis. Thus, patients with P16(ink4a) negative penile cancer, particularly those with lymph node metastases, may warrant closer observation after surgery.