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Objective: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND)., Patients and Methods: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints., Results: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND., Conclusions: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Modified and superficial inguinal lymph node dissection (MILD and SILD) are the 2 widely used templates for surgical staging of clinically node negative (cN0) penile cancer (PeCa); however, no previous reports have compared their outcomes. We compared these 2 surgical templates for oncological outcomes and complications., Materials and Methods: We retrospectively reviewed records of cN0 PeCa patients who underwent MILD/SILD at our cancer care center from January 2013 to December 2019. Patients who developed a penile recurrence during follow up were excluded from analysis of oncological outcomes. The 2 groups (MILD and SILD) were compared for baseline clinico-pathological characteristics. The primary outcome was the groin recurrence free survival (gRFS). Secondary outcomes included the false negative rate (FNR) and disease free survival (DFS) for both templates and also the post-operative wound related complication., Results: Of the 146 patients with intermediate and high risk N0 PeCa, 74 (50.7%) and 72 (49.3%) underwent MILD and SILD respectively. The 2 groups were comparable with regards to the distribution of T stage, tumor grade and the proportion of intermediate and high-risk patients. At a median follow up of 34 months (47 for SILD and 23 for MILD), a total of 5 groin recurrences were encountered; all of them occurred in the MILD group. The gRFS and DFS for the MILD group was 93.2% and 91.8% respectively; while that for the SILD group was 100% and 94.4% respectively. Too few events had occurred to determine any statistically significant difference. The FNR for MILD and SILD was 26.3% and 0% respectively. The overall complication rate was significantly higher in the SILD group (46% vs 20.3%, p=0.001), especially for Clavien Dindo 3A complications., Conclusion: MILD can fail to pick up micro-metastatic disease in a small proportion of cN0 PeCa patients, while SILD provides better oncological clearance with no groin recurrences. This oncological superiority comes at the cost of a higher incidence of wound-related complications., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: To evaluate the role of unilateral inguinal lymph-node dissection (ILND) plus contralateral dynamic sentinel node biopsy (DSNB) vs. bilateral ILND in clinical N1 (cN1) penile squamous cell carcinoma (peSCC) patients., Material and Methods: Within our institutional database (1980-2020, included), we identified 61 consecutive cT1-4 cN1 cM0 patients with histological confirmed peSCC who underwent either unilateral ILND plus DSNB (26) or bilateral ILND (35)., Results: Median age was 54 years (Interquartile range [IQR]: 48-60 years). Median follow-up was 68 months (IQR 21-105 months). Most patients had pT1 (23 %) or pT2 (54.1%), as well as G2 (47.5%) or G3 (23%) tumors, while lymphovascular invasion (LVI) was present in 67.1% of cases. Considering a cN1 and a cN0 groin, overall 57 out of 61 patients (93.5%) had nodal disease in the cN1 groin. Conversely, only 14 out of 61 patients (22.9%) had nodal disease in the cN0 groin. 5-year IR-free survival was 91% (Confidence interval [CI] 80%-100%) for bilateral ILND group and 88% (CI 73%-100%) for the ipsilateral ILND plus DSNB group (P-value 0.8). Conversely, 5-year CSS was 76% (CI 62%-92%) for bilateral ILND group and 78% (CI 63%-97%) for the ipsilateral ILND plus contralateral DSNB group (P-value 0.9)., Conclusions: In patients with cN1 peSCC the risk of occult contralateral nodal disease is comparable to cN0 high risk peSCC and the gold standard, namely bilateral ILND, may be replaced by unilateral ILND and contralateral DSNB without affecting positive node detection, IRRs and CSS., Competing Interests: Conflict of Interest Nicola Nicolai certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video endoscopic, and robotic-assisted techniques have been utilized so far. In this review, we aim to describe available minimally invasive surgical approaches for ILND, and review their outcomes and complications., Methods: The PubMed, Wiley Online Library, and Science Direct databases were reviewed in February 2020 to find relevant studies published in English within 2000-2020., Findings: There are different minimally invasive platforms available to accomplish dissection of inguinal nodes without jeopardizing oncological results while minimizing postoperative complications. Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy are safe and achieve the same nodal yield, a surrogate metric for oncological adequacy. When compared to open technique, Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy may offer faster postoperative recovery and fewer postoperative complications including wound dehiscence, necrosis, and infection. The relatively high rate and severity of postoperative complications hinders utilization of recommended ILND for oncologic indications. Minimally invasive approaches, using laparoscopic or robotic-assisted platforms, show some promise in reducing the morbidity of this procedure while achieving adequate short and intermediate term oncological outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate the local recurrence rates of men treated with Mohs microsurgery (MMS) for penile carcinoma. The secondary outcome was surgical complications from the MMS procedure or the subsequent reconstructive procedures., Materials and Methods: All patients from 2010 to 2020 with penile carcinoma at our institution were seen in a multidisciplinary setting. Patients with Ta, Tis, T1, and T2 disease were considered candidates for MMS. Clinical and pathologic data were collected for analysis. Local recurrence rates were stratified by stage and complications reported per the Clavien-Dindo Grade., Results: A total of 43 patients met inclusion criteria. The median age at diagnosis was 64 years. Stage distribution was Ta in 4.7%, Tis in 58.1%, T1a in 14.0%, T1b in 7.0%, and T2 in 16.3%. No patients had a positive surgical margin after MMS. The overall local recurrence rate was 2% (n = 1) at a median of 47 months. Local recurrence rates at 1, 3, and 5 years for Ta, Tis, and T1 patients were 0%. Local recurrence rates for T2 patients were 14% at 1 year. Complications occurred in 12% (n = 5), all of which were Clavien-Dindo ≤ III., Conclusions: MMS provides effective local control for Ta, Tis, and T1 penile cancer with an overall local recurrence rate of 2% and an acceptable complication rate. A multi-disciplinary team involving urologic oncology, reconstructive urology, and MMS is essential to patient management., Competing Interests: Conflicts of interest The other authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The majority of penile malignant tumors are squamous cell carcinomas. They are pathologically defined as epithelial neoplasms originating in the squamous cells of the inner mucosal lining of the glans, coronal sulcus or foreskin. Tumor location and site of origin is preferentially in glans (70%) followed by foreskin (25%) and coronal sulcus (5%). Despite the variable geographic distribution, pathological features of penile carcinomas in areas of high- and low-risk are similar. Penile tumors are morphologically heterogeneous. A major advance, based on biological, etiological and prognostic factors, is the 2016 WHO classification separating epithelial penile neoplasia, precancerous and invasive, in non-HPV and HPV-related., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Due to its rarity and lack of prospective studies, clinical evidence for the management of the inguinal lymphatic nodal basin with radiation therapy in penile cancer (PeCa) has been limited. In this report, we review the current literature and further investigated the landscape of radiation sensitivity in nodal metastases of PeCa utilizing our well-established genome-based radiosensitivity index (RSI) platform. We hypothesized that optimal therapeutic gain could be achieved in PeCa stratified by the combination of clinicopathological parameters, genomic heterogeneity, and RSI-based radiation dose prescription (RxRSI). Similar to primary PeCa lesions, we found that the majority of PeCa nodal metastases are genomically radioresistant with significant heterogeneity. RxRSI should be considered to inform and optimize the radiation therapy dose prescription to the individual tumor biology., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Penile aesthetics after partial penectomy (PP) for penile cancer (PC), significantly affect a patient's health-related quality of life (HRQoL), self-esteem, and sexual function. Satisfactory reconstruction has become a major milestone in the treatment of these patients., Methods: Clinical charts of all patients that underwent PP and reconstruction with an inverted urethral flap (IUF) were reviewed. The primary endpoints were recurrence-free survival (RFS), overall survival (OS), and progression-free survival (PFS) which were graphically represented by Kaplan-Meier estimates. The key secondary endpoints were Health-related quality of life (HRQoL), erectile function, and lower urinary tract symptoms., Results: Between May 2007 and December 2019, 74 patients with PC underwent PP and IUF reconstruction. The median age was 62 years (IQR 52-76), median follow-up was 72 months (IQR 38-121). Twenty-nine patients (39.2%) underwent inguinal lymph node dissection, 62 (83.8%) underwent dynamic sentinel lymph node biopsy. Kaplan-Meier estimates of OS, RFS, and PFS showed a 6-year OS of 86.5%, 6-year RFS of 90.5%, and a 6-year PFS of 85.1%. Regarding functional outcomes, we found a mean global health score of 84.6% ± 10.4 at the EQ-5D-3L-VAS. The mean Voiding score of the ICIQ-MLUTS was 1.7 ± 3.2 and a mean IIEF-5 score of 17.3 ± 7., Conclusions: To the best of our knowledge, we report the largest cohort in the literature of PP with IUF reconstruction. These results are important since early-stage PC is the most common stage at diagnosis. In carefully selected patients' preservation of a longer urethral stump to allow for the inverted flap is safe and does not compromise oncological outcomes while preserving HRQoL., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To perform a systematic review and meta-analysis evaluating the peri-operative outcomes, complications, and oncological outcomes of Robotic-Assisted Video-Endoscopic Inguinal Lymphadenectomy (RAVEIL)/Video-Endoscopic Inguinal Lymphadenectomy (VEIL) with Open Inguinal Lymph-Node Dissection (OILND) for management of inguinal lymph-nodes in carcinoma of the penis., Methods: A comprehensive literature search was performed in January 2021 using the PubMed, Embase, and Cochrane databases. Data from human studies comparing RAVEIL/VEIL vs. OILND in carcinoma of penis published in English was extracted and analyzed by two independent authors., Results: Two Randomised Controlled Trials and 6 cohort studies were included in the meta-analysis. RAVEIL/VEIL group exhibited increased operative time (Mean Difference [MD] = 15.28 [14.19; 16.38], P < 0.001), shorter hospital stay (MD = -1.06 [-1.14; -0.98], P < 0.001), and decreased duration of drainage (MD = -2.82 [-3.21; -2.43], P < 0.001), wound infection (Odds Ratio [OR] = 0.15 [0.08; 0.27], P < 0.001), skin necrosis (OR = 0.12 [0.05; 0.28], P < 0.001), lymphedema (OR = 0.41 [0.24; 0.72], P = 0.002), and major complications (OR = 0.11 [0.05; 0.24], P < 0.001) as compared to OILND group. Recurrence rate and number of deaths were comparable in both the groups. RAVEIL/VEIL groups showed slightly larger lymph-node yield (MD = 0.44 [0.18; 0.70], P < 0.001) as compared to OILND group., Conclusion: RAVEIL/VEIL has lesser skin complications, lymphedema, and better lymph-node yield as compared to OILND. It is comparable in terms of lymphocele and recurrence. It has lesser hospital stay and duration of drainage but owing to heterogeneity, the results should be interpreted with caution. Further studies are required to determine long-term oncological outcomes like overall survival and disease-specific survival., Competing Interests: Conflict of interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the feasibility, safety, and efficiency of bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer., Materials and Methods: We reviewed retrospectively the records of 65 patients who underwent inguinal lymph nodes dissection (ILND) for penile cancer from January 2012 to May 2019. Treatments included open ILND (OILND, 19 patients), video-endoscopic inguinal lymphadenectomy (VEIL) using single laparoscopy (S-VEIL, 24 patients), and VEIL using double laparoscopies (D-VEIL, 22 patients). We evaluated the peri-operative and short-term oncological outcomes of the three groups., Results: The mean operative time of D-VEIL (105.91 ± 10.87 minutes) was significantly shorter than the other two groups, OILND shorter than S-VEIL (160.47 ± 13.74 minutes, 191.67 ± 17.80 minutes, respectively) (P < 0.001). Intraoperative blood loss in the S-VEIL and D-VEIL groups were 53.54 ± 8.78 and 48.41 ± 13.22 ml, respectively; they were significantly lower than that of the OILND group (99.74 ± 9.64 ml; P < 0.001). The numbers of unilateral and total lymph nodes harvested were similar in all groups. The complication rates in the S-VEIL group (4.2%) and the D-VEIL group (4.5%) were significantly lower than that in the OILND group (63.2%; P < 0.001). Compared with open surgery (13.53 ± 1.74 days for hospitalization; 11.37 ± 1.92 days for the left side of drain, 11.95 ± 1.84 days for the right side), the two VEIL groups had significantly shorter drainage tube residence time (7.42 ± 2.02 and 7.32 ± 1.52 days, respectively for the left side; 7.63 ± 1.81 and 7.27 ± 1.58 days, respectively for the right side), shorter postoperative hospitalization (9.46 ± 1.64 and 9.00 ± 1.83 days, respectively) (P < 0.001). There were no statistically significant differences in rates of regional recurrence and short-term survival among the three groups., Conclusion: Bilateral inguinal lymphadenectomy using double laparoscopies simultaneously can provide adequate oncological outcomes safely and efficiently, and carry significantly lower morbidity than OILND, at a median follow-up of 33.5 months. It is a more time-saving surgical approach for penile cancer patients who need bilateral ILND., Competing Interests: Conflict of interest All the authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To report long-term oncological outcomes after penile-sparing surgery (PSS) for superficial (Ta-Tis) or initially invasive (T1) penile cancer patients., Methods: We retrospectively analysed 85 patients with Ta/Tis/T1cN0cM0 penile cancer (1996-2018). All patients underwent PSS: circumcision, excision or laser ablation. First, Kaplan-Meier plots and multivariable Cox regression models tested tumor recurrence rates (any local/regional/metastatic). Second, Kaplan-Meier plots depicted progression-free survival (≥T2 or N1-3 or M1 disease)., Results: Median (IQR) follow-up time was 64 (48-95) months. Overall, 48 (56%) patients experienced tumor recurrence. Median (IQR) time to tumor recurrence was 34 (7-52) months. Higher recurrence rates were observed for Tis (65%) and T1 (64%), compared to Ta (40%), but these differences were not significant on multivariable Cox regression analyses (HR:2.0 with 95% CI [0.9-5.1] and HR:2.2 with 95% CI [0.9-5.9], respectively). Moreover, higher recurrence rates were observed for G2-3 tumors (74%), compared to G1 (57%), but these differences were not significant on multivariable Cox regression analyses (HR:1.6; 95% CI [0.8-3.2]). During follow-up, 15 (17.5%) vs. 18 (21.2%) vs. 10 (11.5%) patients underwent 1 vs. 2 vs. ≥3 PSS. Moreover, 26 (30.6%) and 4 (4.7%) men were treated with glansectomy and partial/total penile amputation due to local progression, tumor size or patient preference. Additionally, 24 (28%) men underwent invasive nodal staging. Last, 22 (25.9%) patients experienced disease progression. Median (IQR) time to disease progression was 51 (31-82) months., Conclusion: Patients treated with PSS for newly diagnosed superficial or initially invasive squamous cell carcinoma of the penis should be informed about the non-negligible risk of tumor recurrence and disease progression over time. In consequence, strict follow-up protocols are needed., Competing Interests: Conflicts of interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: We reviewed the medical and surgical management and long-term outcomes for patients diagnosed with penoscrotal extramammary Pagets disease (EMPD) within an eUROGEN centre., Patients and Methods: Retrospective review of cases from an institutional database with biopsy proven penoscrotal EMPD., Results: A total of 10 patients were identified with penoscrotal EMPD over a 10-year period. Two patients had a previous history of gastrointestinal and urogenital cancers (20%) and no synchronous or metachronous cancers were identified. Eight patients with non-invasive EMPD (80%) underwent wide local excision of the affected skin, with at least a 5mm macroscopic resection margin and in selected cases simultaneous multiple mapping biopsies around the lesion were performed. Residual disease was present at the margins in seven patients (87.5%), of which three required further surgical excision or adjuvant topical immunotherapy (42.8%). Recurrence after complete excision was 12.5% and was successfully treated with topical imiquimod immunotherapy and CO 2 laser therapy. Two patients (20%) had invasive carcinoma and metastatic disease at diagnosis., Conclusion: Reported recurrence rates of non-invasive penoscrotal EMPD are high and residual disease is present in most cases requiring either close clinical surveillance or adjuvant treatment. We propose an algorithm in the management of this rare disease., Competing Interests: Conflict of interest We declare no completing interest., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Perineal urethrostomy (PU) is often the definitive form of urinary diversion in patients with locally-advanced or anatomically unfavorable penile cancer (PC) requiring total penectomy. Here, we report post-operative PU-related complications and PU stenosis rates after total penectomy with PU in a large multicenter cohort of PC patients., Methods: We retrospectively reviewed the medical records of 299 patients who underwent PU as a means of urinary diversion for primary PC across seven international centers from 2000 to 2020. The Clavien-Dindo grading system was used to record 30-day post-operative complications. Cumulative incidence of stenosis was evaluated using the Kaplan-Meier method., Results: Median patient age was 67 years (interquartile range (IQR) 58-74), and median follow-up was 19 months (IQR 7.2-57). A total of 58 patients (19%) developed a 30-day post-operative complication, of which 45 (79%) were deemed minor (CD Grade I and II). Wound infection (11%; CD grade I-III) and dehiscence (4.0%; CD grade I-III) were the more common complications. The overall incidence of stenosis was 12% (35/299 patients), of which 26 (74%) needed surgical revision (probability of stenosis revision at one year of 9.3%, median time until the revision: 6.1 months (IQR 3.0-13)). Only two stenoses were seen after two years of follow-up., Conclusion: We present the most extensive series of PU in the management of PC to date. Wound infections of the primary surgical site were the most common complication. Stenosis occurred mostly within one and a half years after treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Inguinal lymph node (ILN) staging and therapeutic procedures are important for the diagnosis and management of suspected Inguinal lymph node metastasis in the setting of penile cancer. Morbidity associated with inguinal lymph node dissection (ILND) and the lack of standardization in its perioperative management are both significant. In this study, we aimed to define current management approaches and potential opportunities for improving outcomes., Methods and Materials: A questionnaire was developed with 16 questions regarding pre, peri, and postoperative management of patients undergoing ILND. The questionnaire was approved by the Society of Urologic Oncology (SUO) Questionnaire Committee, which facilitated its dissemination through an initial email and a follow-up reminder to 1,003 members. The study was conducted from July to August, 2020., Results: Of the 1,003 SUO members invited to participate, 93 responded (9.3% response rate); 49% performed 1 to 2 ILNDs annually, and 60% chose open ILND for high-risk primary cancer cN0. For suspicious lymph nodes > 2 cm, 69% preferred ILND, 86% preoperative systemic neoadjuvant chemotherapy, followed by surgery for bulky inguinal metastasis, and 84% used perioperative antibiotics (ABX), 53% of whom discontinued ABX 24 hours after surgery. Prophylactic anticoagulation was used by 78% of respondents, and 60% stopped it after ambulation. Specific ligation of lymphatics (versus none) was used by 82% of respondents, 55% obtained frozen sections, and 94% used inguinal drains. A saphenous sparing technique was used by 75% of respondents. An incisional wound vacuum device was used by 17% of respondents. Compression stockings and/or referral to a lymphedema specialist were used to manage postoperative lymphedema by 61% of respondents., Conclusions: Responses to a penile lymphadenectomy survey were relatively low and were primarily from the academic surgeon subset of the SUO. Significant consensus ( ≥ 70%) was noted for neoadjuvant chemotherapy for bulky nodal metastasis prior to surgery, perioperative antibiotic use, ligation of lymphatics, drain placement, and saphenous sparing dissection techniques. Other evidenced-based strategies that could decrease morbidity were rarely used, including dynamic sentinel node biopsy, incisional wound vacuums, and lymphedema prevention. Prospective trials are needed to validate and resolve existing treatment paradigms and to optimize perioperative pathways to reduce complications in penile cancer management., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: We determined whether a clinicopathological nomogram is able to predict the risk of pelvic lymph node metastasis (LNM) in penile cancer patients after inguinal lymph node dissection (ILND)., Methods: Ninety-eight patients with bilateral ILND who underwent pelvic lymphadenectomy at 10 centers were retrospectively analyzed. The most predictive features in the nomogram were selected by the stepwise logistic regression method and then tested and verified by multivariate logistic regression analyses. The nomogram was assessed using concordance indices and calibration curves., Results: Of the 181 pelvic basins, pelvic LNM was observed in 52 packages (43 patients). Bilateral pelvic LNM was present in 9 patients (9/43, 20.9%). There was no crossover metastatic spread from one inguinal side to the other pelvic side. Age, previous resection, the biopsy procedure for inguinal lymph nodes, vascular invasion, and ipsilateral inguinal lymph node status were all independent risk factors for pelvic LNM (all P < 0.05) in the multivariate logistic regression analysis. The nomogram exhibited a good probability for survival agreement, with a concordance index of 0.868 (95% CI: 0.813-0.922)., Conclusions: A novel nomogram suggests that the risk of pelvic LNM can be effectively predicted in penile carcinoma patients and may provide a useful guide for clinicians. Further external validation is needed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic-related constraints on healthcare access have raised concerns about adverse outcomes from delayed treatment, including the risk of cancer progression and other complications. Further, concerns were raised about a potentially significant backlog of patients in need of cancer care due to the pandemic-related delays in healthcare, further exacerbating any potential adverse outcomes. Delayed access to surgery is particularly relevant to urologic oncology since one-third of new cancers in men (20% overall) arise from the genitourinary (GU) tract and surgery is often the primary treatment. Herein, we summarize the prepandemic literature on deferred surgery for GU cancers and risk of disease progression. The aforementioned data on delayed surgery were gathered in the context of systemic delays present in certain healthcare systems, or occasionally, due to planned deferral in suboptimal surgical candidates. These data provide indirect, but sufficient insight to develop triage schemas for prioritization of uro-oncological cases. Herein, we outline the extent to which the pandemic-related triage guidelines had influenced urologic practice in various regions. To study the adverse outcomes in the pandemic-era, a survey of urologic oncologists was conducted regarding modifications in their initial management of urologic cancers and any delay-related adverse outcomes. While the adverse effects directly from COVID-19 related delays will become apparent in the coming years, the results showing short-term outcomes are quite instructive. Since cancer care was assigned a higher priority at most centers, this strategy may have avoided significant delays in care and limited the anticipated negative impact of pandemic-related constraints., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC)., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used., Results: 666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045)., Conclusions: The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To characterize the treatment trends and outcomes in clinical stage T1 penile cancer using the National Cancer Database (NCDB)., Methods: The National Cancer Database was queried for all men with cT1 penile cancer from 2004 to 2015. Patients were categorized as cT1a or cT1b. Treatment was categorized as no treatment, local therapy (including penile sparing therapies), partial penectomy, or radical penectomy. Trends in treatment were analyzed over time and in correlation with stage and demographic variables. Stage and treatment type were evaluated in respect to pathological outcomes and survival., Results: A total of 2,484 men were identified with cT1 penile cancer, 90.1% of which had cT1a disease. The most common treatments were local therapy for cT1a and partial penectomy for cT1b. Over the time period studied, use of local therapy decreased while use of partial or radical penectomy increased. Patients treated at low volume facilities were more likely to undergo no treatment (8.0% vs. 6.5% in high volume) or local therapy (49.9% vs. 41.5% in high volume, P < 0.001). Local therapy was associated with increased risk of positive margin (odds ratio 4.7, P < 0.001) and positive margin was associated with a trend toward decreased overall survival (P = 0.07)., Conclusions: In the past decade, there has been decreased use of local therapy and increased use of partial or radical penectomy in cT1 penile cancer. Men treated at low volume facilities are more likely to be treated with local therapy which is associated with increased rates of positive margins and may also be associated with a trend toward decreased overall survival. Centralization of care in T1 penile cancer may lead to improved outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Surgical management of penile cancer depends on accurate margin assessment and staging. Advanced optical imaging technologies may improve penile biopsy and organ-sparing treatment. We evaluated the feasibility of confocal laser endomicroscopy for intraoperative assessment of benign and malignant penile tissue., Patients and Methods: With institutional review board approval, 11 patients were recruited, 9 with suspected penile cancer, and 2 healthy controls. Confocal laser endomicroscopy using a 2.6-mm fiber-optic probe was performed at 1 or 2 procedures on all subjects, for 13 imaging procedures. Fluorescein was administered intravenously approximately 3 minutes prior to imaging for contrast. Video sequences from in vivo (n = 12) and ex vivo (n = 6) imaging were obtained of normal glans, suspicious lesions, and surgical margins. Images were processed, annotated, characterized, and correlated with standard hematoxylin and eosin histopathology., Results: No adverse events related to imaging were reported. Distinguishing features of benign and malignant penile tissue could be identified by confocal laser endomicroscopy. Normal skin had cells of uniform size and shape, with distinct cytoplasmic membranes consistent with squamous epithelium. Malignant lesions were characterized by disorganized, crowded cells of various size and shape, lack of distinct cytoplasmic membranes, and hazy, moth-eaten appearance. The transition from normal to abnormal squamous epithelium could be identified., Conclusions: We report the initial feasibility of intraoperative confocal laser endomicroscopy for penile cancer optical biopsy. Pending further evaluation, confocal laser endomicroscopy could serve as an adjunct or replacement to conventional frozen section pathology for management of penile cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We analyzed adherence rates to contemporary guidelines regarding inguinal lymph node dissection (ILND) for squamous cell carcinoma of the penis, as well as ILND association with cancer specific mortality (CSM), and complication rates., Materials and Methods: Within the Surveillance, Epidemiology, and End Results and the National Inpatient Sample databases, 943 and 317 nonmetastatic penile cancer patients (1998-2015) were respectively identified. Multivariable analyses focused on ILND rates, CSM, and complication rates. Inverse probability of treatment weighting adjustment was used in CSM analyses., Results: Within the Surveillance, Epidemiology, and End Results database, ILND was performed in 233 (24.7%) patients. ILND rates did not vary over time (P = 0.2). In the overall cohort (n = 943), ILND was an independent predictor of lower CSM (hazards ratio [HR]: 0.42; P < 0.001). In Multivariable CSM analyses stratified according to N-stage, ILND was associated with lower CSM in N1 (HR: 0.25; P < 0.001) and N2-3 (HR: 0.42; P = 0.01), but not in N0 patients. Within the National Inpatient Sample database, presence of LN invasion (LNI) was associated with longer hospitalization (odds ratio: 1.27, P = 0.01), but not with higher complications or in-hospital mortality., Conclusions: The adherence to guidelines for ILND was low (24.7%), and did not change over time. Nonetheless, a CSM benefit related to ILND was observed in N1, N2, and N3 patients. Complication rates and in-hospital mortality did not differ according to LNI. However, hospital stay may be longer in LNI patients. Finally, it should be noted that lack of distinction between clinical and pathological N-stage represents an important limitation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The nodal status is a strong predictor for clinical outcome in patients with penile cancer. We aimed to evaluate the association between preoperative plasma IGFBP2 levels and nodal status in patients with penile squamous cell carcinoma (PSCC)., Methods: This retrospective study enrolled 56 penile cancer patients who underwent penectomy between 2015 and 2017. Preoperative plasma IGFBP2 levels were detected by enzyme linked immunosorbent assay, which was analyzed in association with clinicopathological parameters (age, body mass index, pathological grade, phimosis, histological subtype, tumor stage, and nodal status). Univariable and Multivariable Cox regression analysis was conducted to identify the prognostic factors that influence disease free survival in PSCC. CCK8 assay and clonogenic assay were used to evaluate the cell viability and tumorigenic potential of PSCC cell line, respectively; wound healing assay, and transwell invasion assay were conducted to evaluate the effect of IGFBP2 depletion on cell migration and invasion in PSCC cells; IGFBP2 protein expression was analyzed by Western blotting., Results: Plasma IGFBP2 levels were markedly higher in preoperative PSCC than those in healthy male subjects (P = 0.0007). Penectomy led to a significant reduction of plasma IGFBP2 levels in PSCC patients (P = 0.0098). Preoperative plasma IGFBP2 levels were significantly associated with nodal status of PSCC (P < 0.0001). At the cutoff value of 486.2 ng/ml, preoperative plasma IGFBP2 produced a sensitivity of 80.8% and a specificity of 86.7% to discriminate nodal metastasis. Preoperative plasma IGFBP2 levels could serve as independent prognostic factor for disease free survival in PSCC (P = 0.001). Further, knockdown of IGFBP2 expression suppressed cell growth, inhibited clonogenesis, and attenuated cell migration and invasion in Penl1 cells; depletion of IGFBP2 expression attenuated the levels of p-AKT and p-ERK1/2, while increased the expression of p16 and cleaved caspase-3 in Penl1 cells. Silencing IGFBP2 also led to a considerable decline of MMP2/9 levels in culture supernatant of Penl1 cells., Conclusion: Higher preoperative plasma IGFBP2 was closely associated with nodal metastasis, which might serve as a useful diagnostic and prognostic biomarker for clinical management of PSCC. IGFBP2 might play an important role in the malignant progression of PSCC. Therapeutic strategies targeting IGFBP2-related signaling pathways may have a therapeutic benefit in PSCC patients., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Penile cancer is a rare disease in Europe and North America. Cancer registry data were used to estimate the incidence, mortality, and survival of penile cancer in Saxony, Germany., Methods: Data on incidence were analyzed for the period 1961 to 2012 and mortality for the period 1990 to 2012. Trend analyses of incidence and mortality were performed using joinpoint regression. Survival rates for primary penile cancer (ICD-10 C60) were estimated; overall, by T stage, UICC stage, and by year of diagnosis for the years 1963 to 2012., Results: Age-standardized incidence increased from 1.2 per 100,000 in 1961 to 1.8 per 100,000 in 2012, with a statistically significant increase between 2003 and 2012 (annual percent change: 4.66; 95% confidence interval, CI 0.62-8.86). There was a statistically significant negative trend in mortality between 1990 and 2012 (annual percent change: -3.46, 95% CI -5.21 to -1.67). A total of 430 new cases of penile cancer were registered between 2003 and 2012, with 63% of all penile cancers occurring in men aged 60 to 79 years. Almost half of those cases were located at the glans penis. The overall relative 5-year survival for the years of diagnosis 2003 to 2012 was 72.4% (95% CI 64.8%-80.0%). Relative 5-year survival decreased with higher UICC stages (I: 96%, 95% CI 84.7%-107.3%; II: 86.3%, 95% CI 71.0%-101.5%; III: 39.6%, 95% CI 19.9%-59.3%; IV: 20.3%, 95% CI 2.4%-38.2%)., Conclusion: The incidence of penile cancer in Saxony has increased in recent years, while mortality has decreased. However, survival rates have remained constant over time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Penile squamous cell carcinoma is a rare cancer in men. The main prognosticators of survival for penile cancer patients remain the presence and the extent of lymph node metastasis. While radical inguinal lymphadenectomy has been the cornerstone of regional lymph node management for many years, it is still associated with significant morbidity and psychological distress. Recent developments in penile squamous cell carcinoma management have been met with some controversy in the urologic oncology community. Herein, we review the current controversies and developments on the role of inguinal lymphadenectomy for penile cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers., Materials and Methods: Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes., Results: Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease., Conclusions: EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To define the anatomical location of sentinel lymph nodes (SLN) in penile cancer patients based on Daseler's original zonal description using a combination of single photon emission computed tomography-computed tomography (SPECT-CT), cross sectional imaging and lymphoscintigraphy and characterise the limits of Zone V., Materials and Methods: Patients with primary penile cancer ≥T1G2 were included in the study. A total of 113 groins with impalpable inguinal lymph nodes (cN0) underwent planar lymphoscintigraphy and SPECT-CT. The sentinel lymph nodes were mapped on cross sectional imaging according to Daseler's anatomical description. Using measurements from fixed anatomical landmarks, a custom-made software program mapped the SLNs. SLNs were mapped to the previously undefined Zone V using 3 approaches to avoid observational bias: (a) as perceived by the uroradiologist, (b) limiting Zone V to a 5 mm radius from the sapheno-femoral junction or (c) using a 10 mm radius from the sapheno-femoral junction., Results: Using SPECT-CT, drainage to the groins was seen in 109 of the 113 cN0 groins (96.5%). The majority of the SLNs were located in the central and superior quadrants with 38.2% lying within Zone I, 45% in Zone II and 13% in Zone V. More importantly, sentinel lymph nodes were still localised to the inferior zones with 3% located in Zone III and 0.8% in Zone IV., Conclusions: Using a hybrid of SPECT-CT, cross sectional imaging and lymphoscintigraphy we have demonstrated that SLNs may be located in the inferior zones. We also define the limits of Zone V as an area of 5 mm radius from the sapheno-femoral junction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and Phosphatase and tensin homolog (PTEN) tumor-related proteins in equine penile papillomas (ePP) and squamous cell carcinomas (ePSCC), the occurrence of epithelial-mesenchymal transition (EMT) at the invasion front (IF) and compare our findings with current knowledge on human penile squamous cell carcinoma (hPSCC)., Material and Methods: We analyzed, by immunohistochemistry in 45 equine penile proliferative epithelial lesions, the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and PTEN using monoclonal antibodies. Tumors were histopathologically classified as well-differentiated or poorly differentiated using the IF grading scheme. Semiquantitative analysis was performed to determine down or up-regulation of the proteins and association with histopathological characteristics were statistically investigated using Mann-Whitney U test and/or Spearman's tests., Results: COX-2 was neo-expressed in 86.6% of the cases and expression progressively increased from ePP to ePSCC (P = 0.0003) and from well to poorly differentiated (P = 0.033). High COX-2 expression was associated with a high mitotic index (MI) (P = 0.026). In contrast to normal epidermis, ePSCC had very low E-cadherin expression in 64% of the cases (P = 0.0005). Vimentin was neo-expressed in 65% of poorly differentiated ePSCC at the IF indicating EMT. Cytoplasmic 14-3-3σ protein expression was reduced in 42% of the ePSCC and additionally, nuclear expression of 14-3-3σ in neoplastic keratinocytes and in the cytoplasm of stromal fibroblasts at the IF was features only found in ePSCC. PTEN protein showed a tendency to be decreased or lost in ePSCC., Conclusions: Our study provides evidence of molecular abnormalities in ePSCC similar to those reported for human PSCC. The occurrence of EMT at the IF is a common event in ePSCC. Naturally occurring ePSCC could serve as a valuable preclinical animal model to explore upcoming therapeutic options for hPSCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine whether a specific lymph node yield (LNY) affects overall survival (OS) in patients with penile cancer., Materials and Methods: Using the National Cancer Database, we identified 364 men diagnosed with pSCC who underwent ILND between 2004 and 2013. Men diagnosed on autopsy or at the time of death, patients with preoperative chemotherapy or radiotherapy, M+ and N3 disease, or with less than 3-month of follow-up were excluded. Kaplan-Meier analysis was used to compare Overall Survival (OS). A multivariable Cox regression model was developed to assess predictors of OS., Results: The median number of LN retrieved was 16 (IQR: 9-23). There was no significant difference in race, stage, grade for men with LNY ≤15 vs. >15. However, men with LNY ≤15 were significantly older than those with LNY >15 (65 vs. 59 years, p<0.001). On multivariable analysis, radical surgery, age, N+ disease, and LNY ≤15 were independent predictors of worse OS. Patients with LNY ≤15 showed significantly worse 5-year OS versus those with LNY >15 (49% vs. 67%, p=0.008). Nodal density (ND) ≥12.5% was also associated with decreased 5-year OS versus ND <12.5% (31% vs. 70%, p<0.0001)., Conclusions: LNY following ILND for pSCC appears to be an independent predictor of OS. A total LNY of >15 following ILND may have a beneficial impact on OS and serve as the threshold for defining an adequate ILND., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the usage of surgical staging of inguinal lymph nodes (SSILNs) in the United States for intermediate to high-risk, clinically localized penile squamous cell cancer (SCC), to explore patient and hospital factors associated with omission of this staging, and to evaluate the effect on survival., Patients and Methods: Retrospective, observational study using the National Cancer Database from 2004 to 2014 of 1,689 men diagnosed with pT1b-T3, cN0 penile SCC, who by current guidelines should receive SSILNs-either by inguinal lymph node (ILN) dissection or sentinel node biopsy. Binomial logistic regression analysis was performed to determine predictors of SSILNs. Multivariate Cox regression analysis was performed to determine the impact of SSILNs on survival in the overall and propensity-score matched patient populations., Results: Only 25.3% of patients underwent SSILNs. Increasing patient age, higher comorbidity status, lower pathologic stage, Medicaid insurance, and treatment at a nonacademic facility were independent factors associated with the omission of SSILNs. Omission of SSILNs was an independent predictor of overall mortality, both in the overall patient population after multivariate adjustment, HR = 1.46 [(95% CI: 1.14-1.88), P = 0.003], and in the propensity-score matched adjusted population, HR = 1.59 [(95% CI: 1.20-2.13), P = 0.001]. Limitations include an inability to distinguish biopsy from ILN dissection and those inherent in observational study design., Conclusion: Utilization of SSILN for penile SCC is low and has not changed significantly since the publication of guidelines in the United States. In particular, nonacademic institutions were less likely to adhere to recommendations for performance of SSILNs. We found the omission of SSILNs is associated with a significant increase in mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To investigate predictive pathological factors for local recurrence (LR) after glansectomy for penile squamous cell carcinoma (SCC) and to develop a risk score for prediction of LR after glansectomy., Patients and Methods: In this retrospective study, we analyzed 117 patients operated between February 2005 and January 2016 in a supraregional penile cancer center in the UK for LR after glansectomy and glans reconstruction. Univariate and multivariate Cox proportional hazards regression was used to identify 4 prognostic indicators for LR. The hazard ratio (HR) of LR was estimated in Kaplan-Meier analysis, and based on these data, we designed a postoperative model for prediction of LR based on 3 risk groups., Results: Median follow-up period was 33.7 (95% CI: 26.8-40.3) months; 12.8% of the patients experienced LR. Univariate Cox proportional hazards regression revealed that the risk factors for recurrence were the presence of perineural invasion, carcinoma in situ, positive margin on definitive pathology, and high-grade disease. Based on Kaplan-Meier analysis stratified by number of factors present, we defined 3 risk groups for LR: low (0,1 risk factors) as reference, intermediate (2,3 risk factors) with HR of 13.9 (95% CI: 1.81-107.04, P = 0.0115), or high risk (all 4 risk factors present) with a HR of 34.2 (95% CI: 3.07-381.81, P = 0,0041). Limitations include the retrospective design and low number of events inherent to the rare nature of penile SCC., Conclusions: Perineural invasion, carcinoma in situ, positive definitive margins, and the presence of high-grade SCC predict LR following glansectomy. These factors can be used to stratify patients into low-, intermediate-, and high-risk groups for recurrence which may be used to tailor follow-up., (Copyright © 2017. Published by Elsevier Inc.)

Background: Sentinel lymph node (SLN) biopsy represents a well-established diagnostic tool for the assessment of lymphatic metastasis. Correct pre- and intraoperative visualization of SLN is of the utmost importance to ensure the safety and feasibility of the procedure. Aim of this study was to evaluate the diagnostic value of preoperative SLN imaging via single photon emission computed tomography/computed tomography (SPECT/CT) and planar scintigraphy in patients with penile carcinoma with nonpalpable inguinal lymph nodes., Materials and Methods: After peritumoral intradermal tracer injection (150MBq/4.05mCi Tc-99m nanocolloid), we acquired planar scintigraphies including indirect body contouring using a twin head gamma camera. Subsequently we acquired SPECT/CT images of the abdomen via a hybrid system. Prospective evaluation of 52 groins in 26 examined patients was done for all image files obtained with both techniques by 2 trained experts in consensual assessment., Results: A total of 71 SLNs in 37 groins were identified by means of planar scintigraphy. In these images, no radiolabeled lymph nodes were visualized in 15 out of 52 groins (28.8%). The SPECT/CT images showed a total of 82 SLNs in 42 groins. In 19.2% (10 of the 52 groins), there was no visualization of lymph nodes in SPECT/CT. 8 SLNs in 7 groins that were visualized in the planar technique were found to be false positive by SPECT/CT. In total, 19 SLNs in 16 groins that were overlooked by planar imaging could only be detected by SPECT/CT. In contrast to planar scintigraphy, SPECT/CT imaging enabled clear and precise anatomical localization of SLNs in all 42 groins where radiolabeled SLNs were visible. Even under consideration of all lymphatic drainage regions, statistical evaluation showed a significantly higher number of detected SLNs with SPECT/CT in comparison to the planar technique (P = 0.0022)., Conclusion: In these patients SPECT/CT is capable of visualizing SLNs that cannot be detected with planar imaging. The SPECT/CT technique reduces the number of false positive findings from planar SLN imaging and is able to show anatomic SLN localization more precisely. If possible, preoperative SLN imaging should be performed by means of the SPECT/CT technique in patients with this tumor entity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The role of adjuvant radiation in advanced penile cancer (PC) is unknown. We used the National Cancer Database (NCDB) to determine factors associated with receiving adjuvant radiation (aXRT) and their influence on prognosis in men who underwent inguinal lymph node dissection (ILND) for stage III disease., Materials and Methods: We queried the NCDB from 1998-2012 for all men with PC who had pathologic nodal status and aXRT data available. Clinical and pathologic variables associated with aXRT were examined using chi-square testing. Logistic regression evaluated the odds of receiving aXRT while multivariate Cox regression analysis evaluated the influence of aXRT on overall survival (OS)., Results: A total of 589 patients underwent ILND for stage III PC with 23% (N = 136) receiving aXRT. Mean age was 61.8 ±13.7 years. Factors associated with receiving aXRT included higher pathologic nodal stage (MV OR 1.85, 95% CI: 1.13-3.05), while greater distance of travel (MV OR 0.48, 95% CI: 0.25-0.92), and treatment in an academic setting (MV OR 0.53, 95% CI: 0.35-0.81) were inversely associated with receiving aXRT. On Cox regression analysis, aXRT improved OS (combined HR 0.58, 95% CI: 0.39-0.86), which appeared to have been driven by higher nodal burden (N2: HR 0.53, 95% CI: 0.32-0.88; N1: HR 1.36, 95% CI: 0.60-3.09)., Conclusions: Determinants of aXRT delivery in stage III PC appear to be related to the proximity to community cancer centers and greater nodal burden. We find evidence of a survival benefit with the use of aXRT, particularly in those with higher nodal stage. Multi-institutional studies are needed to confirm these findings and improve treatment algorithms for high-stage PC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To describe the survival outcomes of organ sparing surgery (OSS), partial penectomy (PP), and total penectomy (TP) in pathological stage pT1/pT2 penile cancer (PC) as reported in the United States National Cancer Data Base., Methods: Patients with pT1/pT2 PC, treated with surgery as their primary treatment modality were classified into 3 groups according to the type of surgery into OSS, PP, and TP. Patient and tumor characteristics of the groups were compared using bivariate analysis, and Cox- proportional hazard model was used for survival analysis., Results: A total of 4,238 patients were examined. There were 1,211, 2,360, and 584 patients in the OSS, PP, and TP groups, respectively. In 83 patients, the type of surgery was missing. The 5- and 10-year overall survival rates for OSS, PP, and TP were 88% and 74% vs. 85% and 72% vs. 79% and 63%, respectively (P ≤ 0.001). In addition, in a multivariable model for predictors of patient survival, OSS did not predict poor patient survival (hazard ratio = 0.88, CI: 0.64-1.21)., Conclusions: Our results demonstrate, at national level, OSS in early stage PC provided comparable outcomes in selected patients compared to PP and TP. Also, organ preservation was not associated with any significant reduction in patient survival in early stage PC. Our results help with early stage PC patient informed treatment decisions and anticipated outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To evaluate whether socioeconomic factors affect pathologic stage, treatment delays, pathologic upstaging, and overall survival (OS) in patients with penile cancer (PC)., Patients and Methods: A total of 13,283 eligible patients diagnosed with PC from 1998 to 2012 were identified from the National Cancer Database. Socioeconomic, demographic and pathologic variables were used in multivariable regression models to identify predictors of pathologic T stage ≥2, pathologic lymph node positivity, cT to pT upstaging, treatment delays, and OS., Results: A 5-year OS was 61.5% with a median follow-up of 41.7 months. Pathologic T stage ≥2 was identified in 3,521 patients (27.2%), 1,173 (9.2%) had ≥pN1 and 388 (7.9%) experienced cT to pT upstaging. Variables associated with a higher likelihood of pathologic T stage ≥2 included no insurance (OR = 1.79, P<0.001), lower higher education based on zip code (OR = 1.13, P = 0.027), black race (OR = 1.17, P = 0.046) and Hispanic ethnicity (OR = 1.66, P<0.001). Patients with Hispanic ethnicity (OR = 1.46; P<0.001) or living in nonmetropolitan areas were more likely to have ≥pN1 (P = 0.001). Lack of insurance was associated with cT to pT upstaging (OR = 2.05, P = 0.001) as was living in an urban vs. metropolitan area (OR = 1.35, P = 0.031). In addition to TNM stage, black vs. white race (HR = 1.56, P<0.001), living in an urban vs. metropolitan area (hazard ratio [HR] = 1.18, P = 0.022), age (HR = 1.04, P<0.001) and Charlson score (HR = 1.49, P<0.001) were associated with lower OS., Conclusion: Socioeconomic variables including no insurance, lower education, race, Hispanic ethnicity, and nonmetropolitan residence were found to be poor prognostic factors. Increased educational awareness of this rare disease may help reduce delays in diagnosis, improve prognosis and ultimately prevent deaths among socioeconomically disadvantaged men with PC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To investigate contemporary survival trends in penile cancer., Methods: The National Cancer Database was queried for men with penile cancer diagnosed between 1998 and 2009. Patient, tumor, treatment, and facility characteristics were obtained. Overall survival (OS) was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model for all cases and stratified by stage., Results: A total of 8,122 cases of penile cancer were reported from 1998 to 2009 in the National Cancer Database. Complete staging, survival, and covariate data were available for 5,043 cases. The estimated crude 5-year OS for the entire cohort was 61.0%. For all patients, no significant differences in crude 5-year OS were detected between 2006 to 2009 and 2002 to 2005 compared to 1998 to 2001. On multivariable analysis, OS did not significantly differ across all eras. Regional lymph node dissection was associated with improved OS (hazard ratio [HR] = 0.777, P ≤ 0.0001). In patients who underwent lymph node dissection, dissection of ≥8 nodes significantly improved survival (HR = 0.672; P = 0.0011). Additional modeling stratified by stage revealed that OS for stage II cancers increased significantly in 2006 to 2009 compared to 1998 to 2001 (HR = 0.714; P = 0.0034)., Conclusions: Survival in penile cancer has remained unchanged as a whole and for each stage, except for stage II disease. An improved survival trend was detected in stage II penile cancer. Performing a lymph node dissection, especially extensive dissections, may benefit long-term survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: We have previously shown the importance of the complement system in differentiating between patients with squamous cell carcinoma of the penis (SCCP) and controls. These patients had low expression of C3a and C4 fragments. Therefore, in this study, we investigated the complement protein C3a as a potential circulating biomarker in these patients by a commercially available enzyme-linked immunosorbent assay (ELISA) test., Patients and Methods: Plasma samples from 39 patients with SCCP, 15 patients with prostate cancer, and 50 healthy male subjects were evaluated using the ELISA-Bioscience OptEIA Kit human anti-C3a (BD). The nonparametric Mann-Whitney test was used for comparison of means among the groups., Results: The complement protein C3a was found down expressed in patients with SCCP (P<0.05) in comparison to either subjects with good health or subjects with prostate cancer., Conclusion: Experimental validation of the down expression of C3a was well succeeded using a commercial ELISA kit. Complement system fragment C3a is down expressed in patients with SCCP. Besides, C3a is also low expressed in the plasma of patients with initial prostate cancer when compared to healthy subjects. These results suggest that the innate immune response might be suppressed in patients with these malignancies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To validate the clinical and prognostic significance of our proposed pN3 subclassification in penile cancer., Materials and Methods: A retrospective analysis of 509 patients with penile cancer undergoing partial, total penectomy or inguinal lymphadenectomy or pelvic lymphadenectomy at Sun Yat-sen University Cancer Center was reevaluated by pathologists. pN3 stage was subclassified into pN3a (extranodal extension of any inguinal lymph node [LN] metastasis only) and pN3b (pelvic LN metastasis). The t test and chi-square test were applied to assess the comparability of pN3a and pN3b with clinicopathologic features. Univariable and multivariable statistical analyses were used to evaluate prognostic effect with cancer-specific survival., Results: Among 509 patients, 71 patients with pN3 stage cancer were divided into 39 with pN3a and 32 with pN3b. The median number of LNs removed and the number of positive LNs were 27 and 3, respectively. The 3-year cancer-specific survival in pN3a and pN3b groups was significantly different at 47.9% and 28.6% (P = 0.003). In multivariable analysis, pN3 subclassification was an independent predictor for cancer-specific mortality (hazard ratio = 2.77; 95% CI: 1.170-6.558; P = 0.02). Adding pN3 subclassification to a multivariable model including pT stage, tumor grade, side involvement, lymphovascular invasion, number of positive LNs, and adjuvant therapy increased predictive accuracy for cancer-specific mortality from 0.665 to 0.695 (P<0.001)., Conclusions: Subclassification helps better distinguish patients with pN3 penile cancer with increased risk of disease progression and cancer-related mortality., (Copyright © 2017. Published by Elsevier Inc.)

Objective: To determine the locoregional management of penile cancer before the introduction of NCCN guidelines and how much shift in practice patterns is required to meet the guidelines., Methods: The National Cancer Data Base was queried to identify 6,396 patients with squamous cell carcinoma of the penis diagnosed between 2004 and 2013. The cohort was divided into management groups based on the NCCN guidelines: cTa and cTis (cTa/is), pT1 low grade (T1LG), pT1 high grade (T1HG), and pT2 or greater (T234). These groups were analyzed to determine if management of locoregional disease complies with the 2016 NCCN guidelines and logistic regression analyses were performed to determine factors associated with adherence., Results: Nationwide management of the primary tumor closely follows the NCCN guidelines, with 96.9% adherence for cTa/is, 91.4% for T1LG, and 94.2% for T234. Management of regional lymph nodes (LNs) was inadequate with only 62.9% of patients with clinical N1 or N2 disease undergoing regional LN dissection (LND). The percentage of patients with known LN metastases who received regional LND increased over time (46.2% in 2004 to 69.4% in 2013, P = 0.034). Patients treated at community cancer programs (odds ratio [OR] = 0.26, 95% CI: 0.19-0.35), comprehensive community cancer programs (OR = 0.34, 95% CI: 0.29-0.41), and integrated network cancer programs (OR = 0.36, 95% CI: 0.25-0.52) were significantly less likely to receive LND compared with patients treated at academic comprehensive cancer programs., Conclusions: Before the introduction of NCCN guidelines, national practice patterns for the management of the primary tumor were consistent with the recommendations. However, the management of regional LNs deviated from the guidelines, reflecting an area for improvement., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Our aims were to evaluate epithelial-mesenchymal transition (EMT) as a useful prognostic marker in penile carcinoma (PC), and establish an objective criterion to define EMT in PC specimens., Materials and Methods: A total of 149 consecutive cases surgically treated for PC were retrospectively selected. E-cadherin (E-CAD) and vimentin immunohistochemical expressions were evaluated. A combined analysis was performed using both markers to determine EMT status. To establish a normal control to E-CAD expression, we included 14 cases from circumcisions from patients without any neoplastic disease and 77 cases of tumor-free margins. The analyses of tumor samples were evaluated in 2 different areas of the tumor. The first one was in the tumor core. The second analyses were performed on the deepest infiltrative edge of the tumor, nominated invasion front. Cases were classified into EMT absent group, partial EMT group and complete EMT group. Overall survival (OS) and cancer-specific survival (CSS) were analyzed. Kaplan-Meier curves and the log-rank test were used. Cox proportional hazards model was used to determine which variables influenced survival., Results: Tumor specimens presented a significant loss of expression of E-CAD when compared with normal epithelium. Vimentin expression in more than 10% of tumor cells was observed in 50 cases. EMT status was associated with histologic grade, pattern of invasion, lymph node metastasis, and perineural and vascular invasion. Further, 10-year OS and CSS rates in patients with presence and absence of complete EMT status were 38.0% and 55.6%; and 48.0% and 91.9%, respectively. EMT status significantly affected CSS and OS rates even after patients were grouped based on lymph node involvement status. The presence of complete EMT status was associated with both CSS and OS rates. Patients in the complete EMT group had a higher risk of death from cancer (hazard ratio = 7.6, P<0.001) and overall death (hazard ratio = 3.0, P<0.001)., Conclusion: Our study represents an evidence of the prognostic effect of EMT in PC. We encourage the study of EMT markers in other centers to validate our findings and confirm its importance in such tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: We determined whether adjuvant chemotherapy (AC) would be associated with improved survival after lymph node dissection (LND) for patients with penile cancer (PeCa) who have positive pelvic lymph nodes (PPLNs)., Methods: We retrospectively identified patients across 4 centers with penile squamous cell carcinoma who underwent LND from 1978 to 2013 and were found to have PPLNs. Patients who received chemotherapy before surgery or in the presence of recurrent disease were excluded. Cox regression was used to evaluate the association of AC with overall survival (OS), which was estimated using the Kaplan-Meier method. Differences in OS were determined with the log-rank test., Results: During the study period, 141 patients who underwent LND for PeCa had PPLNs, and 84 of them met inclusion criteria. Median number of PPLNs was 2 (interquartile range [IQR]: 4-7), with 10% of cases occurring bilaterally and 55% having pelvic extranodal extension. AC was used in 36 (43%) patients. Patients who received AC were younger (P = 0.014), had less-aggressive penile tumor pathology (P<0.01), were less likely to receive adjuvant radiation (P<0.01), had less bilateral inguinal disease (P = 0.019), and had more inguinal extranodal extension (P = 0.042). Median follow-up was 12.1 months. Estimated median OS was 21.7 months (IQR: 11.8-104) in patients who received AC vs. 10.1 (IQR: 5.6-48.1) in those who did not (P = 0.048). AC was independently associated with improved OS on multivariate analysis (hazard ratio: 0.40; 95% CI: 0.19-0.87; P = 0.021)., Conclusions: AC is associated with improved OS in patients with PeCa who have PPLNs after LND. Prospective studies are needed to demonstrate causality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Lymph node staging is important in many urologic malignancies. The lack of a sufficiently accurate noninvasive lymph node staging modality has proven to be challenging as most urologic malignancies rely on surgical lymph node removal for regional staging. Penile cancer has been a model disease for the development of the sentinel node concept, which has subsequently been successfully adapted to breast cancer and melanoma studies. Currently, the sentinel node technique is standardized in many centers and under development for new indications. The introduction of near-infrared cameras and fluorescence techniques has paved the way for robot-assisted laparoscopic sentinel node biopsies in prostate cancer, urinary bladder cancer, and renal cancer. Fluorescence techniques have increased visual guidance towards lymph nodes during surgery and have challenged previously established templates for surgical lymph node removal. This review discusses the history of our understanding of the lymphatic system and the development of the sentinel node concept and highlights the importance of early and minimally invasive regional lymph node staging. Contemporary data on sentinel node biopsy in each of the urologic malignancies are assessed. Current trends towards robot-assisted sentinel lymph node removal are discussed, and the diagnostic accuracy and oncologic safety of sentinel node procedures are addressed. In an era of several new sentinel node indications, the importance of proper case selection, protocolled regimen, consequent follow-up, and back-up strategies in the case of radiotracer-silent or nonvisualized regions is stressed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer., Methods: We retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models., Results: Median follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P<0.05). Stratifying pN+ patients as above versus below the LND threshold demonstrated significant differences in 5-year DSS: 81.2% versus 24.4% (P < 0.001). In multivariate models including known prognostic factors, LND was a statistically significant independent predictor of DSS rate (hazard ratio = 4.31 and 3.96 for above vs. below the LND threshold, respectively)., Conclusions: The removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease., Patients and Methods: Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model., Results: The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors., Conclusions: In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors., (© 2013 Published by Elsevier Inc.)

Objective: Prediction of lymph node (LN) metastases in penile invasive cancer relies on clinical features and histologic characteristics of the primary tumor. Correct prediction, however, is difficult, as only 50% patients undergoing lymphadenectomies will have LN metastases. In 2009, the tumor, nodes, metastases (TNM) classification for staging of early penile cancers was revised. We tested the predictive accuracy of the revised TNM classification in a low incidence area for penile carcinoma., Materials and Methods: The presence of LN metastases in 76 men with pT1 penile cancers was correlated with the 2009 TNM subclassification, which is based on a combined evaluation of tumor grade and lymphatic invasion, but also with individual parameters, such as histologic grade, lymphatic invasion, perineural invasion, invasion depth, growth pattern and human papilloma virus (HPV) status., Results: 76pT1 penile cancers were reclassified into 31pT1a squamous cell carcinomas (SCC) and 45pT1b (41 SCC; 4 clear-cell carcinomas); 12/22 men (55%; 8 SCC, 4 clear-cell carcinomas) undergoing lymphadenectomy for enlarged inguinal lymph nodes had metastases, 54 patients without enlarged LN and lymphadenectomies had no LN metastases during follow-up of median 47 months. Statistically, clear cell differentiation of the primary carcinoma was highly associated with metastases (100% clear-cell carcinomas vs. 11% SCC) and poor survival (50% vs. 5.5%). Among conventional SCC, only lymphatic invasion showed a highly significant association with metastases with 100% specificity. The 2009 TNM classification, tumor grade alone, perineural invasion, growth pattern, invasion depth or HPV status could not predict LN status. Lymphadenectomy for enlarged LN resulted in 100% sensitivity and 42% predictive probability for identifying metastases and a 16% false positive rate. Statistically, survival correlated significantly with clear-cell differentiation and with lymphatic invasion in both clear-cell carcinomas and conventional SCC., Conclusions: Penile clear-cell carcinomas are more aggressive cancers than SCC. Our observation suggests a benefit of a prophylactic lymphadenectomy for patients with clear-cell carcinomas. Among conventional SCC, only lymphatic invasion predicted LN metastases. Neither tumor grade alone nor perineural invasion, growth pattern, depth of invasion, and subgrouping according to the revised TNM classification correlated with metastases. Clinical evaluation of the LN status was superior to histologic risk stratification., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Inguinal lymph node dissection (ILND) for the treatment of metastatic penile squamous cell carcinoma (SCC) has historically been associated with significant morbidity. This review addresses the surgical principles and techniques to decrease its perioperative morbidity, while optimizing its oncologic outcomes., Materials and Methods: A review of the English scientific literature from 1966 to present was conducted using the PubMed search engine as well as of additional cited works not initially noted in the search using as keywords penile cancer, inguinal lymph node dissection, inguinal lymph node metastasis, morbidity, and complications., Results: The contemporary outcomes of ILND in the context of penile cancer have built on the significant contributions made by surgeons and scientists worldwide. In this review, we provide a comprehensive overview of the principles of ILND optimizing oncological outcomes, while minimizing its attributable morbidity. It is hoped this review will serve as a benchmark for clinicians to approach this often highly aggressive tumor phenotype., Conclusions: ILND remains an important diagnostic and therapeutic procedure for patients with penile SCC, as contemporary ILND series have reported a decrease in its associated morbidity, with the potential for further treatment outcomes in years to come. ILND can in appropriately selected patients render them disease-free, thus justifying its associated morbidity., (Copyright © 2013 Elsevier Inc. All rights reserved.)