Impact of Variant Histology on Oncological Outcomes in Upper Tract Urothelial Carcinoma: Results From the ROBUUST Collaborative Group.

INTRODUCTION: Oncologic implications of variant histology (VH) have been extensively studied in bladder cancer; however, further investigation is needed in upper tract urothelial carcinoma (UTUC). Our study aims to evaluate the impact of VH on oncological outcomes in UTUC patients treated with radical nephroureterectomy (RNU). METHODS: A retrospective analysis was performed on patients who underwent a robotic or laparoscopic RNU for UTUC using the ROBUUST database, a multi-institutional collaborative including 17 centers worldwide. Logistic regression was used to assess the effect of VH on urothelial recurrence (bladder, contralateral upper tract), metastasis, and survival following RNU. RESULTS: A total of 687 patients were included in this study. Median (IQR) age was 71 (64-78) years and 470 (68%) had organ confined disease. VH was present in 70 (10.2%) patients. In a median follow-up of 16 months, the incidence of urothelial recurrence, metastasis, and mortality was 26.8%, 15.3%, and 11.8%, respectively. VH was associated with increased risk of metastasis (HR 4.3, P <.0001) and death (HR 2.0, P =.046). In multivariable analysis, VH was noted to be an independent risk factor for metastasis (HR 1.8, P =.03) but not for urothelial recurrence (HR 0.99, P =.97) or death (HR 1.4, P =.2). CONCLUSION: Variant histology can be found in 10% of patients with UTUC and is an independent risk factor for metastasis following RNU. Overall survival rates and the risk of urothelial recurrence in the bladder or contralateral kidney are not affected by the presence of VH.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center

ABSTRACT Purpose To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. Materials and Methods Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. Results A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. Conclusion The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center.

PURPOSE: To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. MATERIALS AND METHODS: Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. RESULTS: A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. CONCLUSION: The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Risk of residual cancer after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumour and International Germ Cell Cancer Cooperative Group intermediate/poor prognosis: A multi-institutional retrospective cohort study.

INTRODUCTION: Current guidelines recommend surveillance in metastatic non-seminomatous germ cell tumour patients treated with first-line-chemotherapy and a complete clinical response (normalisation of serum tumour markers and residual masses <1 cm). However, this recommendation is based on a series including patients with good prognosis according to International Germ Cell Cancer Cooperative Group prognostic group (IGCCCG-PG). The aim of this study was to analyse the proportion of residual teratoma and survival among patients with intermediate/poor IGCCCG-PG and a complete clinical response after first-line-chemotherapy. MATERIAL & METHODS: This is a retrospective study of men with intermediate/poor IGCCCG-PG, who had a complete clinical response after first-line chemotherapy. Patients were either followed by surveillance or treated with post-chemotherapy retroperitoneal lymph node dissection (pcRPLND). RESULTS: Between 2009 and 2018, 143 men with intermediate (n = 83) or poor (n = 60) IGCCCG-PG were treated at 11 international centres. Among 33 patients treated with pcRPLND, the specimen showed teratoma and viable cancer in 16 (48%) and 4 (12%). During a median a 7-year follow-up, 20/110 (18%) patients managed with surveillance relapsed, of whom seven (6%) had a retroperitoneal-only relapse versus 2/33 patients managed with pcRPLND relapsed. No difference was observed regarding overall survival (OS) among men treated with pcRPLND or surveillance (5-year OS, 93% and 89%, p-value = 0.35). The median time-to-recurrence among men on surveillance was 1.3 years (range: 0.3-9.1), and the most common sites of relapses included retroperitoneum (11%), chest (5%), and bones (4%). CONCLUSIONS: While most men with intermediate/poor IGCCCG-PG harbour teratoma/cancer in the retroperitoneum despite a complete response to first-line-chemotherapy, only 6% managed with surveillance relapsed in the retroperitoneum. There was no significant difference in OS between the two groups.

Recurrence patterns in bladder cancer patients with no residual disease (pT0N0) at radical cystectomy: A 20-year experience.

OBJECTIVE: To examine the oncological outcomes and recurrence patterns in patients with no residual disease at the time of radical cystectomy (RC). METHODS: A retrospective review of our IRB-approved bladder cancer database identified patients who underwent RC between 2000 and 2019 and were found to have no residual disease (pT0N0), either following neoadjuvant chemotherapy (NAC) or transurethral resection (TURBT) alone. The primary outcome was recurrence-free survival (RFS). Regression models assessed factors influencing recurrence, and a detailed description of recurrence patterns was compiled. RESULTS: From a total of 2222 patients, 234 (10.5%) were included with a median age of 67 years. NAC was used in 89 (38%) patients and 145 (62%) cases were rendered pT0 following TURBT alone. At a median follow-up of 44 months, there were 16 (6.8%) recurrences, 10 (63%) of which occurred in the ypT0 group. None of the patients with clinical Ta/Tis disease had a recurrence after RC. The median time to recurrence was 9 months. Ninety-one percent (10/11) of recurrences in the ypT0 group were within 2 years of cystectomy, while half of the recurrences in the pT0 group occurred after 2 years. Patients with ypT0 had worse 2- and 5-year RFS compared to the pT0 group (85% and 84% vs. 99% and 95%, respectively; P = 0.003). Variant histology was noted in 49 (21%) patients; the recurrence rate was higher in this subgroup compared to those with pure urothelial carcinoma (12.2% vs. 5.4%, P = 0.02). Lung metastasis and involvement of distant organs, while rare, were noted at similar rates in both groups. CONCLUSION: Patients with pT0N0 pathology at the time of cystectomy should prudently undergo long-term surveillance as recurrence and metastasis can still develop up to 4 years after surgery. Patients achieving ypT0 after NAC exhibit worse prognosis and shorter times to recurrence, closer follow-up may be considered.

Distal ureter and bladder cuff excision using the "Keyhole Technique" during Robotic Radical Nephroureterectomy

ABSTRACT Introduction: Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all urothelial tumors (1). Radical nephroureterectomy (RNU) remains the standard treatment for high, and low-grade UTUC (2). Although the open approach has been considered the gold standard, robotic techniques have shown comparable oncological outcomes with potential advantages in terms of peri-operative morbidity (3). Materials and Methods: We present a novel "Keyhole" technique for management of distal ureter and bladder cuff during robotic RNU. This technique allows the surgeon to directly visualize the ureteric orifices, delineate resection borders, and maintain oncologic principles of en-bloc excision without necessitating secondary cystotomy incision or concomitant endoscopic procedure. Descriptive demographic characteristics, surgical, pathological, and oncological outcomes were analyzed. Complications were reported using the Clavien-Dindo classification system. Results: Between 2015 and 2020, ten patients underwent robotic RNU with bladder cuff excision using the Keyhole technique (single-dock, single-position). Median age was 75 years. Eight patients underwent surgery for right-sided tumors. Median operative time, estimated blood loss, and length of hospital stay were 287 min, 100 mL, and 3 days, respectively. No intraoperative complications occurred, and one grade II complication occurred during the 90-day postoperative period. All patients had high-grade UTUC, being 90% pure urothelial. Bladder recurrences occurred in 30% of patients with an overall median follow-up of 11.2 months. Conclusions: Keyhole technique for the management of distal ureter and bladder cuff during RNU represents a feasible approach with minimal 90-day complications and low bladder recurrence rate at centers of experience.

Primary Retroperitoneal Lymph Node Dissection for Patients With Pathologic Stage II Nonseminomatous Germ Cell Tumor-N1, N2, and N3 Disease: Is Adjuvant Chemotherapy Necessary?

PURPOSE: According to National Comprehensive Cancer Network guidelines, adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the risk of relapse in pathologic nodal (pN) stage pN2 or pN3, whereas surveillance is preferred for pN1. We sought to explore the oncologic efficacy of primary RPLND alone for pathologic stage II in nonseminomatous germ cell tumors (NSGCTs) to reduce overtreatment with chemotherapy. METHODS: Patients with pathologic stage II NSGCT after primary RPLND between 2007 and 2017 were identified. Patients were excluded for elevated preoperative serum tumor markers, receipt of AC, or if pure teratoma or primitive neuroectodermal tumor elements were found in the retroperitoneal pathology. RESULTS: We identified 117 patients with active NSGCT in the retroperitoneum after primary RPLND. We excluded seven patients who lacked meaningful follow-up and 13 patients who received AC. There were 97 patients treated with RPLND alone: 41 pN1, 46 pN2, and 10 pN3. In total, 77 of 97 patients had not recurred after a median follow-up time of 52 months. The 2-year recurrence-free survival (RFS) was 80.3%, and the 5-year RFS was 79%. No differences in RFS were noted among nodal stage-pN1, pN2, and pN3-on Kaplan-Meier analysis. Lymphovascular invasion in the orchiectomy specimen, a high-risk pathologic feature, was also predictive of recurrence after primary RPLND. All 20 patients who recurred were treated with first-line chemotherapy and remained continuously disease free. CONCLUSION: Most men with pathologic stage II disease treated with surgery alone in our series never experienced a recurrence. We did not observe a difference in recurrences between patients with pN1 and pN2. The recommendation for AC for pN2 disease may be overtreatment in most patients.

Distal ureter and bladder cuff excision using the "Keyhole Technique" during Robotic Radical Nephroureterectomy.

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all urothelial tumors (1). Radical nephroureterectomy (RNU) remains the standard treatment for high, and low-grade UTUC (2). Although the open approach has been considered the gold standard, robotic techniques have shown comparable oncological outcomes with potential advantages in terms of peri-operative morbidity (3). MATERIALS AND METHODS: We present a novel "Keyhole" technique for management of distal ureter and bladder cuff during robotic RNU. This technique allows the surgeon to directly visualize the ureteric orifices, delineate resection borders, and maintain oncologic principles of en-bloc excision without necessitating secondary cystotomy incision or concomitant endoscopic procedure. Descriptive demographic characteristics, surgical, pathological, and oncological outcomes were analyzed. Complications were reported using the Clavien-Dindo classification system. RESULTS: Between 2015 and 2020, ten patients underwent robotic RNU with bladder cuff excision using the Keyhole technique (single-dock, single-position). Median age was 75 years. Eight patients underwent surgery for right-sided tumors. Median operative time, estimated blood loss, and length of hospital stay were 287 min, 100 mL, and 3 days, respectively. No intraoperative complications occurred, and one grade II complication occurred during the 90-day postoperative period. All patients had high-grade UTUC, being 90% pure urothelial. Bladder recurrences occurred in 30% of patients with an overall median follow-up of 11.2 months. CONCLUSIONS: Keyhole technique for the management of distal ureter and bladder cuff during RNU represents a feasible approach with minimal 90-day complications and low bladder recurrence rate at centers of experience.

Long-term renal function in patients with chronic kidney disease following radical cystectomy and orthotopic neobladder.

OBJECTIVE: To evaluate long-term renal function in patients with chronic kidney disease (CKD) Stage IIIa who underwent radical cystectomy and orthotopic neobladder (RC/ONB) compared to matched controls. PATIENTS AND METHODS: Using our Institutional Review Board-approved institutional database, patients with a glomerular filtration rate (GFR) of 45-59.9 mL/min/1.73 m2 who underwent RC/ONB were identified. A control group of patients with a GFR of ≥60 mL/min/1.73 m2 was selected. Groups were matched based on age, baseline hypertension/diabetes mellitus, perioperative chemotherapy, and preoperative hydronephrosis. A decrease in GFR of >10 mL/min/1.73 m2 during the follow-up was considered significant. A multivariate Cox regression analysis was performed to identify predictors of GFR decline in each group. RESULTS: Of 1237 patients who underwent RC/ONB, 508 patients were included (254 per group). The mean preoperative GFR was 53.3 mL/min/1.73 m2 in the study group and 78.8 mL/min/1.73 m2 in controls. The median follow-up was 3.7 years. During follow-up, GFR stayed at or above baseline in 51% of the study patients compared to 46% of the controls (P = 0.5). The mean time to a significant GFR decline in the study patients was significantly longer compared to the controls (5.6 vs 2 years, respectively; P < 0.001). In multivariate analysis, neoadjuvant chemotherapy was found to be the strongest predictor of a significant GFR decline as well as GFR decline below baseline (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.29, P = 0.004; and HR 2.15, 95% CI 1.4-3.29, P < 0.001, respectively). CONCLUSION: Patients with CKD Stage IIIa who undergo ONB appear to have comparable long-term renal function to those with a GFR of ≥60 mL/min/1.73 m2 . An ONB reconstruction is a safe option for patients with CKD Stage IIIa desiring a continent diversion.

Safety and feasibility of urological procedures in Jehovah's Witness patients.

OBJECTIVES: To describe the safety and feasibility of urological transfusion-free surgeries in Jehovah's Witness patients. METHODS: An institutional review board-approved, retrospective review of Jehovah's Witness patients who underwent urological transfusion-free surgeries between 2003 and 2019 was carried out. Surgeries were stratified into low, intermediate and high risk based on complexity, invasiveness and bleeding potential. Patient demographics, perioperative data and clinical outcomes are reported. RESULTS: A total of 161 Jehovah's Witness patients (median age 63.4 years) underwent 171 transfusion-free surgeries, including 57 (33.3%) in low-, 82 (47.9%) in intermediate- and 32 (18.8%) in high-risk categories. The mean estimated blood loss increased with risk category at 48 mL (range 10-50 mL), 150 mL (range 50-200 mL) and 388 mL (range 137-500 mL), respectively (P < 0.001). Implementing blood augmentation and conservation techniques increased with each risk category (3.5% vs 29% vs 69%, respectively; P < 0.001). Average length of stay increased concordantly at 1.6 days (range 0-12 days), 2.9 days (range 1-13 days) and 5.6 days (range 2-12 days), respectively (P ≤ 0.001). However, there was no increase in complication rates and readmission rates attributed to bleeding among the risk categories at 30 days (P = 0.9 and 0.4, respectively) and 90 days (P = 0.7 and 0.7, respectively). CONCLUSIONS: Transfusion free urological surgery can be safely carried out on Jehovah's Witness patients using contemporary perioperative optimization. Additionally, these techniques can be expanded for use in the general patient population to avoid short- and long-term consequences of perioperative blood transfusion.

A Preoperative Nomogram to Predict Renal Function Insufficiency for Cisplatin-based Adjuvant Chemotherapy Following Minimally Invasive Radical Nephroureterectomy (ROBUUST Collaborative Group).

BACKGROUND: Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU). OBJECTIVE: To create a model predicting renal function decline after minimally invasive RNU. DESIGN, SETTING, AND PARTICIPANTS: A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) <50 ml/min/1.73 m2 at 3 mo after RNU. Patients with baseline eGFR >50 ml/min/1.73 m2 (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR <50 ml/min/1.73 m2 was built based on the coefficients of the least absolute shrinkage and selection operation (LASSO) logistic regression. The discrimination, calibration, and clinical use of the nomogram were investigated. RESULTS AND LIMITATIONS: The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p < 0.001) and cancer-specific death risk (HR: 5.19, p < 0.001) was statistically significant. The limitation mainly lies in its retrospective design. CONCLUSIONS: A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection. PATIENT SUMMARY: We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.

Bladder Recurrence Following Diagnostic Ureteroscopy in Patients Undergoing Nephroureterectomy for Upper Tract Urothelial Cancer: Is Ureteral Access Sheath Protective?

OBJECTIVE: To examine the effect of diagnostic ureteroscopy (URS) and ureteral access sheath usage on bladder recurrence following radical nephroureterectomy (RNU). METHODS: We retrospectively reviewed the records of patients who underwent RNU between 2005 - 2019. Patients with a history of bladder cancer and those without a bladder cuff resection were excluded. Bladder recurrence was the primary outcome and cox regression modeling was used to assess the impact of URS adjusting for other factors. RESULTS: Out of 271 RNU cases, 143 were included with a median age of 73 years (IQR 65 - 80). URS was performed in 104 cases (73%) and a ureteral access sheath was used in 26 (25%). With a median follow-up of 27 months, there were 36 (25%) bladder recurrences. The bladder recurrence rate (median time to recurrence) for patients who had URS vs no URS was 30.8% (9.0 months) and 7.7% (12.1 months), respectively (P = .02). A lower recurrence rate was noted in patients whom a ureteral access sheath was utilized (11.5%) vs those with no access sheath (39.7%, P = .01). Multivariable analysis revealed a significant increase in bladder recurrence if URS was performed prior to RNU (HR 5.6 [1.7 - 18.5], P <.004), however, this effect was mitigated if a ureteral access sheath was used (HR 1.3, [0.3 - 6.4], P = .76). Ureteral stent usage and performing a ureteroscopic biopsy had no significant effect on bladder recurrence. CONCLUSION: Diagnostic URS in patients undergoing RNU for UTUC significantly increases the risk of bladder recurrence. This effect may be mitigated by using a ureteral access sheath.

Risk factors and natural history of parastomal hernia after radical cystectomy and ileal conduit.

OBJECTIVE: To investigate the incidence, risk factors and natural history of parastomal hernia (PSH). MATERIALS AND METHODS: We reviewed the records of patients who underwent radical cystectomy (RC) and ileal conduit (IC) procedure between 2007 and 2020. Patients who had available follow-up computed tomography (CT) imaging were included in this study. All CT scans were re-reviewed for detection of PSH according to Moreno-Matias classification. Patients who developed hernia were followed up and classified into stable or progressive (defined as radiological upgrading and/or need for surgical intervention) groups. Multivariable Cox regression was performed to identify independent predictors of hernia development and progression. RESULTS: A total of 361 patients were included in this study. The incidence of radiological PSH was 30%, graded as I (56.5%), II (12%) and III (31.5%). The median (interquartile range [IQR]) time to radiological hernia was 8 (5-15) months. During the median (IQR) follow-up of 27 (13-47) months in 108 patients with a hernia, 26% patients progressed. The median (IQR) time to progression was 12 (6-21) months. On multivariable analysis, female gender (hazard ratio [HR] 1.86), diabetes (HR 1.81), chronic obstructive pulmonary disease (COPD; HR 1.78) and higher body mass index (BMI; HR 1.07 for each unit) were independent predictors for radiological PSH development. No significant factor was found to be associated with hernia progression. CONCLUSION: Radiological PSH after RC and IC occurred in 30% of patients, a quarter of whom progressed in a median time of 12 months. Female gender, diabetes, COPD and high BMI were independent predictors for radiological hernia development.

Long-Term Oncologic Outcomes after Primary Retroperitoneal Lymph Node Dissection: Minimizing the Need for Adjuvant Chemotherapy.

PURPOSE: We analyzed the oncologic outcomes of men undergoing primary retroperitoneal lymph node dissection and characterized the use of adjuvant chemotherapy and template dissections. MATERIALS AND METHODS: Retrospective review of the Indiana University testis cancer database identified patients who underwent primary retroperitoneal lymph node dissection between January 2007 and December 2017. Patients and providers were contacted to obtain information regarding adjuvant therapy, recurrence and survival. The primary outcome was recurrence-free survival. Kaplan-Meier curves assessed survival differences stratified by pathological stage, template of dissection and use of adjuvant chemotherapy. RESULTS: A total of 274 patients were included in the study. Most men presented with clinical stage I disease (214, 78%). A modified unilateral template was performed in 257 (94%) and bilateral template in 17 (6%). Overall 148 (54%) and 126 (46%) men had pathological stage (PS) I and PS-II disease, respectively. Thirteen patients (10%) with PS-II disease were treated with adjuvant chemotherapy. With a median followup of 55 months only 33 (12%) patients had recurrence. Of the 113 patients with PS-II disease who did not receive chemotherapy 21 (19%) had disease relapse and 81% were cured with surgery alone and never had recurrence. No difference in recurrence-free survival was noted between modified and bilateral template dissections. CONCLUSIONS: The use of adjuvant chemotherapy has been minimal during the last decade. The majority (81%) of men with PS-II disease were cured with retroperitoneal lymph node dissection alone and were able to avoid chemotherapy. Modified unilateral template dissection provided excellent oncologic control while minimizing morbidity.

Penile cancer epidemiology and risk factors: a contemporary review.

PURPOSE OF REVIEW: Our objective is to present an overview of epidemiologic, clinical, and molecular risk factors with a focus on contemporary literature. RECENT FINDINGS: Penile cancer is a rare and aggressive neoplasm that accounts for less than 1% of male malignancies in the United States. Geographical disparities in incidence of disease are evident with high rates concentrated in the developing world (2.8-6.8 per 100 000) where neonatal circumcision is low and socioeconomic conditions predispose patients to multiple risk factors. Western countries have a significantly lower incidence and can be as low as 0.3 per 100 000. Many risk factors have been identified including lack of circumcision, phimosis, balanitis, obesity, lichen sclerosus, smoking, and psoralen UV-A phototherapy. In addition, human papilloma virus (HPV) has been linked to nearly 40% of cases and molecular mediators continue to be investigated. SUMMARY: Although Penile cancer can be a debilitating disease, several of the known risk factors are modifiable. Public health campaigns aimed to increase awareness, promote better hygiene, and deploy HPV vaccines have had varied success at decreasing disease burden. Focus should be placed on implementing such interventions in developing countries and at-risk populations.

Updates on the epidemiology and risk factors for penile cancer.

Penile cancer is a rare neoplasm representing less than 1% of all malignancies in the USA and Europe but is a significant public health hazard in the developing world. Male neonatal circumcision has been associated with a dramatic decrease in penile cancer rates with countries such as Israel, where circumcision is widely performed, having the lowest incidence in the world at <0.1% of malignancies. Many risk factors have been identified for penile cancer including phimosis, lack of circumcision, obesity, lichen sclerosis, chronic inflammation, smoking, UVA phototherapy, socioeconomic status, human papillomavirus (HPV) infection and immune compromised states. The relationship between these factors and invasive disease varies and continues to be investigated. Our objective was to present a contemporary overview of the epidemiology and risk factors for invasive penile cancer.