Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer

ABSTRACT Objective: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). Materials and Methods: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. Results: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. Conclusion: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Predicting Limited Survival Following Inguinal Lymph Node Dissection in Penile Cancer: Should We Revisit the Goals of Care?

OBJECTIVE: Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit. METHODS: Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT). A multivariable Cox proportional hazards model for overall survival (OS) was developed using the NCDB and applied to the INT dataset. Parameters were used to make receiver operating characteristic (ROC) curves. ROC-related criteria were optimized to identify a predictive probability cut point and dichotomize patients from INT into risk groups for limited OS of <6 and <12 months. RESULTS: NCDB had 860 deaths; 105 (5%) at 6 months and 296 (15%) at 12 months. INT had 257 deaths; 56 (8%) at 6 months and 124 (18%) at 12 months. Limited OS was associated with older age, greater T and N stage, and fewer lymph nodes removed. Optimized ROC criteria using the OS <6 months curve best dichotomized INT patients into high-risk group with median OS of 24 months (95% CI 18-34) and low-risk group with median OS of 174 months (95% CI 120-NE). CONCLUSION: We developed a simple model that could be used as a screening tool for early palliative care referral.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer.

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Concomitant vs Staged Therapeutic Inguinal Lymphadenectomy in Clinically Node Positive Penile Squamous Cell Carcinoma: Does It Make a Difference?

PURPOSE: Inguinal lymph node dissection within 3 months of primary tumor resection in penile cancer has been associated with longer recurrence-free and cancer-specific survival. However, the optimal timing and effect of lymphadenectomy performed concurrently at the time of primary lesion management on oncologic outcomes in clinically lymph node positive penile squamous cell carcinoma remains unknown. MATERIALS AND METHODS: An international, multicenter cohort of 966 penile cancer cases was queried for penile squamous cell carcinoma management after the year 2000, clinically lymph node positive status, and performance of penile surgery and inguinal lymph node dissection. Cohorts were stratified as concomitant if inguinal lymph node dissection and penile surgery occurred on the same date or staged when inguinal lymph node dissection was performed after penile resection. Rates and patterns of penile squamous cell carcinoma recurrence were reported. Distant recurrence-free, cancer-specific, and overall survival were estimated using Kaplan-Meier analyses and groups compared with log-rank testing. RESULTS: Of 253 contemporary men with clinically lymph node positive penile squamous cell carcinoma, 96 (38%) underwent concomitant inguinal lymph node dissection and 157 (62%) had inguinal lymph node dissection performed in a staged manner. Penile cancer was most likely to recur distantly (19%) followed by in the groin (14%) or pelvis (5%). There were no differences in distant recurrence-free, cancer-specific, or overall survival between management strategies. Multivariable analysis adjusting for stage, treatment center, and perioperative chemoradiation also demonstrated no recurrence-free, cancer-specific, or overall survival benefit between management strategies. CONCLUSIONS: Inguinal lymph node dissection performed concurrently with excision of the penile tumor for clinically node positive penile squamous cell carcinoma is not associated with differences in recurrence-free, cancer-specific, or overall survival compared to staged lymph node dissection.

Risk factors and survival outcomes for upstaging after inguinal lymph node dissection for cN1 penile squamous cell carcinoma.

OBJECTIVES: To identify incidence and risk factors for upstaging from cN1 to pN2/N3 at inguinal lymphadenectomy (ILND) for penile cancer (pSCC). Our secondary objective is to assess survival outcomes and associations for cN1 patients undergoing ILND. SUBJECTS/PATIENTS AND METHODS: Patients with pT≥1cN1cM0 pSCC who underwent bilateral ILND and had complete data were identified in a multi-institutional international cohort from 8 referral centers in 7 countries diagnosed from 1980 to 2017. Upstaging was defined as pN2/N3 at ILND. Multivariable logistic regression analysis was used to determine associations with upstaging, and Cox multivariable logistic regression analysis to determine associations with overall survival (OS). RESULTS: Of 144 patients were included in the final study population. 84 patients (58%) were upstaged from cN1 to pN2/N3, and 25 (17%) were down staged to pN0. Upstaging was associated with pT3/T4 (OR 4.1, 95%CI 1.5-11.7, P < 0.01) and pTX (OR 7.1, 95CI 1.6-51.1, P = 0.02). Age, smoking status, HPV status, and LVI were not associated with upstaging. Age (HR 1.03/y, 95%CI 1.01-1.06, P < 0.01) and upstaging (HR 2.8, 95%CI 1.3-5.9, P < 0.01) were associated with worse OS. Upstaged patients had a 5-year OS of 49%, compared with 86% for patients who were not upstaged. CONCLUSION: The majority of cN1 pSCC patients harbor a higher-risk disease state than their clinical staging suggests, especially those with higher pT stages. More intensive pre-operative workup may be warranted for these patients to identify upstaging prior to ILND and potentially qualify them for neoadjuvant chemotherapy or clinical trials.

Patterns of Recurrence following Inguinal Lymph Node Dissection for Penile Cancer: Optimizing Surveillance Strategies.

PURPOSE: Our primary objective is to detail the incidence, site, and timing of penile squamous cell carcinoma (pSCC) recurrence after inguinal lymph node dissection (ILND). MATERIALS AND METHODS: We performed a retrospective analysis of 551 patients who underwent ILND for pSCC from 2000 to 2017. The primary outcome was pSCC recurrence after ILND. Recurrences were identified and stratified by site. Timing of recurrence was determined. Multivariable logistic regression analysis determined associations with recurrence. Multivariable Cox regression analysis determined associations with overall survival (OS). Sub-group analysis of the distant recurrences analyzed timing and OS by site of distant recurrence. RESULTS: After ILND pSCC recurred in 176 (31.9%) patients. Median time to recurrence was 10 months for distant recurrences, 12 for inguinal, 10.5 for pelvic, and 44.5 for local. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months of ILND, versus 127 months for local recurrences. Post-ILND recurrence was associated with pN2 (OR 1.99, 95% CI 1.0-4.1), and pN3 (OR 7.2, 95% CI 4.0-13.7). Patients who had local recurrence had similar OS to those without (HR 1.5, 95% CI 0.6-3.8), and worse OS was identified in patients with inguinal (HR 4.5, 95% CI 2.8-7.1), pelvic (HR 2.6, 95% CI 1.5-4.5), or distant (HR 4.0, 95% CI 2.7-5.8) recurrences. Patients with lung recurrences had worse OS than other sites (HR 2.2, 95% CI 1.1-4.3). CONCLUSIONS: Of the patients 31.9% had post-ILND recurrence associated with high pN staging. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months, suggesting surveillance beyond this is low yield. Local recurrences occurred over a longer timeline, emphasizing necessity of long-term surveillance of the primary site.

Association Between Human Papillomavirus Infection and Outcome of Perioperative Nodal Radiotherapy for Penile Carcinoma.

BACKGROUND: Data on the impact of human papillomavirus (HPV) infection status and outcomes for perioperative treatments for patients with lymph node-involved penile squamous-cell carcinoma (PSCC) are lacking. OBJECTIVE: To analyze the benefit from perioperative radiotherapy (RT) for PSCC according to HPV infection status. DESIGN, SETTING, AND PARTICIPANTS: In an international multicenter database of 1254 patients with PSCC who received inguinal lymph node dissection (ILND), 507 had suitable clinical information. INTERVENTION: ILND, with or without chemotherapy or RT for involved lymph nodes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier and restricted mean survival time (RMST) analyses for overall survival (OS) were performed for all patients and after propensity score-matching (PSM; n = 136), for which patient age, histology, type of penile surgical procedure, pathological tumor and nodal stage, ILND laterality, pelvic LND, and perioperative treatment were taken into account when assessing differences between HPV+ and HPV- patients. Finally, we looked at genomic alterations in PSCC using data from the Foundation Medicine database (n = 199) to characterize HPV+ PSCC. RESULTS AND LIMITATIONS: Patients with HPV+ PSCC (n = 86; 17%) had lower clinical N stage (p < 0.001) and inguinal lymph node metastasis density (p < 0.001). Perioperative RT was delivered in 49 patients (9.7%), with the vast majority receiving adjuvant RT (n = 40). HPV+ patients had similar median OS (p = 0.1) but longer RMST than HPV- patients at different time points. Nevertheless, HPV+ patients treated with perioperative RT exhibited longer median OS (p = 0.015) and longer RMST compared to HPV- patients. In the PSM cohorts, HPV+ status remained significantly associated with longer OS after RT. The HPV- PSCC group had a higher frequency of TP53 mutations compared to HPV+ PSCC (75% vs 15%; p < 0.001). The results are limited by the retrospective nature of the data. CONCLUSIONS: Perioperative RT was more effective in the HPV+ PSCC subgroup. Reasons for the enhanced radiosensitivity may be related to the lack of TP53 mutations. PATIENT SUMMARY: We analyzed data from a large multicenter database for patients with penile cancer who had received inguinal lymph node dissection, with or without chemotherapy or radiotherapy. We found that for tumors positive for human papillomavirus (HPV), use of radiotherapy resulted in prolonged survival compared to HPV-negative tumors. On the basis of these results we are inspired to design studies on the use of radiotherapy in HPV-selected patients.

A risk calculator predicting recurrence in lymph node metastatic penile cancer.

OBJECTIVES: To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. PATIENTS AND METHODS: The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. RESULTS: Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low (<19%) 24m-R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment (P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts (P > 0.1). CONCLUSION: Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

Optimising the selection of candidates for neoadjuvant chemotherapy amongst patients with node-positive penile squamous cell carcinoma.

OBJECTIVES: To identify predictors of poor overall survival (OS) amongst patients with penile squamous cell carcinoma (pSCC) with clinical inguinal lymphadenopathy (cN+), in order to define the best candidates for neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Using an international, multicentre database of 924 patients with pSCC, we identified 334 men who harboured cN+ with available clinical and follow-up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative computed tomography (CT) assessment. Fluorine-18 fluorodeoxyglucose positron-emission tomography (18 F-FDG-PET)/CT scan was performed based on clinical judgment of the treating physician. Regression-tree analysis generated a risk stratification tool for prediction of 24-month overall mortality (OM). Kaplan-Meier explored the OS benefit related to the use of NAC according to the regression-tree-stratified subgroups. RESULTS: Overall, 120 (35.9%), 152 (45.5%), and 62 (18.6%) patients harboured cN1, cN2, and cN3 disease. 18 F-FDG-PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal and pelvic nodal PET detection. The median OS was 107 months, with a 24-month OS of 66%. At regression-tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT-detected inguinal and pelvic nodal activity had a higher risk of 24-month OM (>50%). NAC was associated with improved 24-month OS rates (54% vs 33%) only in this subgroup of patients (P = 0.002), which was also confirmed after multivariable adjustment (hazard ratio 0.28, 95% confidence interval 0.13-0.62; P = 0.002). CONCLUSION: Patients with pSCC with cN3 or cN2 and inguinal and pelvic 18F-FDG-PET/CT scan detected disease had higher 24-month OM rates according to our regression-tree model. NAC was associated with improved OS only in these subgroups of patients. Our novel decision model may help to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.

Nomogram-based prediction of overall survival after regional lymph node dissection and the role of perioperative chemotherapy in penile squamous cell carcinoma: A retrospective multicenter study.

OBJECTIVES: To improve the prognostic allocation of patients with penile squamous-cell carcinoma (PSCC) receiving regional lymph node dissection (LND). PATIENTS AND METHODS: An international, multicenter, retrospective study was performed on patients with PSCC who received regional LND, with or without perioperative therapy, from 1980 to 2017. We first used a random forest (RF) method with missing data imputation. Additionally, data were modeled using Cox proportional hazard regression, and a Cox model was also fit including prespecified variables. Based on the latter model, a nomogram for estimating 12-month and 24-month overall survival (OS) was developed. RESULTS: There were 743 patients who received LND at 7 referral centers from Europe, the USA, Brazil, and China. Of these patients, 689 were analyzed: 86 (12.5%) received neoadjuvant chemotherapy (NAC); 171 (24.8%) received adjuvant chemotherapy (AC), and 74 (10.7%) received adjuvant radiotherapy. The variables significantly associated with OS were age (P < 0.001), the pathologically involved/total removed LN ratio (P < 0.001), pN stage (overall P < 0.001), and NAC (P = 0.013). NAC and AC were ineffective in N1-2 patients (clinical and pathological, respectively), whereas they provided OS improvements in N3 patients. Finally, we developed a nomogram predicting 12- and 24-month OS based on prespecified variables (c-index: 0.75). The study is limited by its retrospective nature. CONCLUSIONS: We propose a tool that can be offered as an aid to physicians to enhance decision-making, clinical research, and patient counseling whenever LND is needed for PSCC. Administration of NAC and AC should be restricted to clinical and pathological N3 patients, respectively.

Urine screening by Seldi-Tof, followed by biomarker identification, in a Brazilian cohort of patients with renal cell carcinoma (RCC).

PURPOSE: To screen proteins/peptides in urine of Renal Cell Carcinoma (RCC) patients by SELDI-TOF (Surface Enhanced Laser Desorption Ionization - Time of Flight) in search of possible biomarkers. MATERIAL AND METHODS: Sixty-one urines samples from Clear Cell RCC and Papillary RCC were compared to 29 samples of control urine on CM10 chip. Mass analysis was performed in a ProteinChip Reader PCS 4,000 (Ciphergen Biosystems, Fremont, CA) with the software Ciphergen Express 3.0. All chips were read at low and at high laser energy. For statistical analysis the urine samples were clustered according to the histological classification (Clear Cell and Papillary Carcinoma). For identification urine was loaded on a SDS PAGE gel and bands of most interest were excised, trypsinized and identified by MS/MS. Databank searches were performed in Swiss-Prot database using the MASCOT search algorithm and in Profound. RESULTS: Proteins that were identified from urine of controls included immunoglobulin light chains, albumin, secreted and transmembrane 1 precursor (protein K12), mannan-binding lectin-associated serine protease-2 (MASP-2) and vitelline membrane outer layer 1 isoform 1. Identification of immunoglobulins and isoforms of albumin are quite common by proteomics and therefore cannot be considered as possible molecular markers. K12 and MASP-2 play important physiological roles, while vitellite membrane outer layer 1 role is unknown since it was never purified in humans. CONCLUSIONS: The down expression of Protein K-12 and MASP-2 make them good candidates for RCC urine marker and should be validated in a bigger cohort including the other less common histological RCC subtypes.

Urine screening by Seldi-Tof, followed by biomarker identification, in a Brazilian cohort of patients with Renal Cell Carcinoma (RCC)

Purpose To screen proteins/peptides in urine of Renal Cell Carcinoma (RCC) patients by SELDI-TOF (Surface Enhanced Laser Desorption Ionization - Time of Flight) in search of possible biomarkers. Material and Methods Sixty-one urines samples from Clear Cell RCC and Papillary RCC were compared to 29 samples of control urine on CM10 chip. Mass analysis was performed in a ProteinChip Reader PCS 4,000 (Ciphergen Biosystems, Fremont, CA) with the software Ciphergen Express 3.0. All chips were read at low and at high laser energy. For statistical analysis the urine samples were clustered according to the histological classification (Clear Cell and Papillary Carcinoma). For identification urine was loaded on a SDS PAGE gel and bands of most interest were excised, trypsinized and identified by MS/MS. Databank searches were performed in Swiss-Prot database using the MASCOT search algorithm and in Profound. Results Proteins that were identified from urine of controls included immunoglobulin light chains, albumin, secreted and transmembrane 1 precursor (protein K12), mannan-binding lectin-associated serine protease-2 (MASP-2) and vitelline membrane outer layer 1 isoform 1. Identification of immunoglobulins and isoforms of albumin are quite common by proteomics and therefore cannot be considered as possible molecular markers. K12 and MASP-2 play important physiological roles, while vitellite membrane outer layer 1 role is unknown since it was never purified in humans. Conclusions The down expression of Protein K-12 and MASP-2 make them good candidates for RCC urine marker and should be validated in a bigger cohort including the other less common histological RCC subtypes. .

Prognostic factors in renal cell carcinoma: analysis of 227 patients treated at the Brazilian National Cancer Institute.

PURPOSE: We evaluated the role of several prognostic factors in predicting death and/or progressive disease in patients with renal cell carcinoma. MATERIALS AND METHODS: Between 2004 and 2010, 227 consecutive patients with renal cell carcinoma underwent radical nephrectomy at our Institute. All histological specimens were examined by the same pathologist. We considered certain histological parameters, including histological subtype, conventional Fuhrman grade, presence of sarcomatoid features, adrenal gland infiltration, invasion of the perinephric fat, vascular embolization, collecting system invasion, presence or absence of tumour necrosis (0 %, 1 % to 49 %, or 50 % or greater) and regional lymph node metastasis. RESULTS: Variables significantly associated with death and/or progressive disease on univariate analysis were histological subtype (p = 0.006), Fuhrman grade (p < 0.0001), tumor necrosis (p = 0.009), perinephric fat invasion (p = 0.002), vascular embolization (p = 0.0002), presence of lymph node involvement (p < 0.002), tumor size (p = 0.0006), TNM stage (p < 0.00001) and presence of metastasis (p < 0.00001). In the multivariable model histological subtype, tumor necrosis, lymph node involvement and presence of metastasis were independent risk factors for disease-free survival (p = 0.011, 0.042, 0.025 and p < 0.0001, respectively). CONCLUSION: Histological subtype, tumor necrosis, lymph node involvement and presence of metastasis proved to be independent prognostic factors for disease-free survival. Therefore, the presence and rate of tumor necrosis should always be informed by the pathologist and lymphadenectomy should be performed in all patients.

Prognostic factors in renal cell carcinoma: analysis of 227 patients treated at the Brazilian National Cancer Institute

PURPOSE: We evaluated the role of several prognostic factors in predicting death and/or progressive disease in patients with renal cell carcinoma. MATERIALS AND METHODS: Between 2004 and 2010, 227 consecutive patients with renal cell carcinoma underwent radical nephrectomy at our Institute. All histological specimens were examined by the same pathologist. We considered certain histological parameters, including histological subtype, conventional Fuhrman grade, presence of sarcomatoid features, adrenal gland infiltration, invasion of the perinephric fat, vascular embolization, collecting system invasion, presence or absence of tumour necrosis (0%, 1% to 49%, or 50% or greater) and regional lymph node metastasis. RESULTS: Variables significantly associated with death and/or progressive disease on univariate analysis were histological subtype (p = 0.006), Fuhrman grade (p < 0.0001), tumor necrosis (p = 0.009), perinephric fat invasion (p = 0.002), vascular embolization (p = 0.0002), presence of lymph node involvement (p < 0.002), tumor size (p = 0.0006), TNM stage (p < 0.00001) and presence of metastasis (p < 0.00001). In the multivariable model histological subtype, tumor necrosis, lymph node involvement and presence of metastasis were independent risk factors for disease-free survival (p = 0.011, 0.042, 0.025 and p < 0.0001, respectively). CONCLUSION: Histological subtype, tumor necrosis, lymph node involvement and presence of metastasis proved to be independent prognostic factors for disease-free survival. Therefore, the presence and rate of tumor necrosis should always be informed by the pathologist and lymphadenectomy should be performed in all patients.

Epidemiological aspects of penile cancer in Rio de Janeiro: evaluation of 230 cases.

PURPOSE: To determine epidemiological characteristics of penile cancer in Rio de Janeiro, its associated risk factors and clinical manifestations. PATIENTS AND METHODS: Between 2002 and 2008 we evaluated 230 patients at three public institutions, considering age, ethnicity, birthplace, marital status, educational level, religion, tobacco smoking, presence of phimosis and practice of circumcision. RESULTS: The ages ranged from 25 to 98 years, with an average of 58.35 years. Of the 230 patients, 167 (72.7%) were from the southeast region of Brazil (which includes Rio de Janeiro) and 45 (19.5%) were from the northeast of the country. Most patients were white (67.3%), married (58.6%), smokers (56.5%) and had not completed primary school (71.3%). The predominant religion was Catholic (74.8%). Of the 46 (20%) circumcised patients, only 1 (2.2%) had undergone neonatal circumcision. Grade I tumors were present in 87 (37.8%) of the patients, grade II in 131 (56.9%) and grade III in 12 (5.3%). Lymphovascular embolization was observed in 63 (27.3%) and koilocytosis in 124 (53.9%) patients. Of the total, 41.3% had corpora cavernosa or corpus spongiosum infiltration, and 40 (17.4%) had urethral invasion. Prophylactic lymphadenectomy was performed on 56 (36.1%), therapeutic lymphadenectomy on 84 (54.2%) and hygienic lymphadenectomy for advanced disease on 15 (9.7%) patients. The median time between the lesion onset and clinical diagnosis was 13.2 months. The mean follow up was 28.8 months. CONCLUSION: Most of our patients were born in this state and had low socioeconomic status. Most of them were white men, married, smokers, uncircumcised, of the Catholic faith and in their sixties or older. Their disease was in most cases diagnosed only in the advanced stages.

Epidemiological aspects of penile cancer in Rio de Janeiro: evaluation of 230 cases

PURPOSE: To determine epidemiological characteristics of penile cancer in Rio de Janeiro, its associated risk factors and clinical manifestations. PATIENTS AND METHODS: Between 2002 and 2008 we evaluated 230 patients at three public institutions, considering age, ethnicity, birthplace, marital status, educational level, religion, tobacco smoking, presence of phimosis and practice of circumcision. RESULTS: The ages ranged from 25 to 98 years, with an average of 58.35 years. Of the 230 patients, 167 (72.7 percent) were from the southeast region of Brazil (which includes Rio de Janeiro) and 45 (19.5 percent) were from the northeast of the country. Most patients were white (67.3 percent), married (58.6 percent), smokers (56.5 percent) and had not completed primary school (71.3 percent). The predominant religion was Catholic (74.8 percent). Of the 46 (20 percent) circumcised patients, only 1 (2.2 percent) had undergone neonatal circumcision. Grade I tumors were present in 87 (37.8 percent) of the patients, grade II in 131 (56.9 percent) and grade III in 12 (5.3 percent). Lymphovascular embolization was observed in 63 (27.3 percent) and koilocytosis in 124 (53.9 percent) patients. Of the total, 41.3 percent had corpora cavernosa or corpus spongiosum infiltration, and 40 (17.4 percent) had urethral invasion. Prophylactic lymphadenectomy was performed on 56 (36.1 percent), therapeutic lymphadenectomy on 84 (54.2 percent) and hygienic lymphadenectomy for advanced disease on 15 (9.7 percent) patients. The median time between the lesion onset and clinical diagnosis was 13.2 months. The mean follow up was 28.8 months. CONCLUSION: Most of our patients were born in this state and had low socioeconomic status. Most of them were white men, married, smokers, uncircumcised, of the Catholic faith and in their sixties or older. Their disease was in most cases diagnosed only in the advanced stages.

Renal cell carcinoma and proteomics.

Renal cell carcinoma (RCC) represents 3% of adult malignancies. About 30% of RCC patients develop metastatic disease. So far, drugs cannot significantly increase the survival of these patients. We present a recent review of proteomics and RCC. Proteomic technologies have been used in the research to discover new markers of RCC that might increase survival. Furthermore, newly discovered markers cannot increase patient survival, rather their prognostic value supporting therapeutic decisions or new agents targeted at these new markers. More research is required to develop proteomic technologies and biomarkers for identification and validation.

Human papillomavirus and penile cancers in Rio de Janeiro, Brazil: HPV typing and clinical features.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA in penile cancers in Rio de Janeiro, Brazil. MATERIALS AND METHODS: We studied, prospectively, 80 consecutive cases of patients with penile cancers who underwent surgical treatment at three different Hospitals in Rio de Janeiro between March 1995 and June 2000. Of these patients, 72 were diagnosed with invasive squamous cell carcinoma and 8 patients with verrucous carcinoma. The following parameters were observed: presence or absence of HPV DNA viral type, histological subtypes, clinical stage and overall survival. RESULTS: HPV DNA was detected in 75% of patients with invasive carcinomas and in 50% of patients with verrucous carcinomas. High risk HPVs were detected in 15 of 54 (27.8%) patients with HPV positive invasive tumors and in 1 of 4 (25%) patients with HPV positive verrucous tumors. HPV 16 was the most frequent type observed. No correlation was observed between HPV status and histological subtype (p = 0.51) as well as HPV status and stage stratification (p = 0.88). HPV status was also not significantly associated with the presence of regional metastases (p = 0.89). The overall survival was related to the presence of lymph node metastases (p < 0.0001). CONCLUSIONS: HPV infection may have contributed to malignant transformation in a large proportion of our penile cancer cases but only inguinal metastasis was a prognostic factor for survival in these patients with penile carcinoma.