Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

PURPOSE: Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. MATERIAL AND METHODS: This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. A competing risks survival analysis adjusted for grade, lymphovascular invasion, and stage was performed to assess local recurrence-free survival in patients with penile intraepithelial neoplasia-positive margins and completely negative surgical margins. RESULTS: A negative surgical margin was described in 319 men (85%), whereas penile intraepithelial neoplasia in the surgical margin was found in 59 men (15%). Local recurrence was observed in 30/319 men with a negative surgical margin compared to 11/59 men with penile intraepithelial neoplasia in the surgical margin. Adjusted for T stage and grade, patients with penile intraepithelial neoplasia at the surgical margin had a higher risk to develop a local recurrence than those with a negative surgical margin without penile intraepithelial neoplasia (HR 1.51, 95% CI 1.07-2.12, P = .019). CONCLUSIONS: Men with a penile intraepithelial neoplasia-positive surgical margin have an increased risk to experience local recurrence compared to men with a negative surgical margin and should undergo closer surveillance and/or adjuvant treatment.

Impact of centralization of prostate cancer services on the choice of radical treatment.

OBJECTIVE: To assess the impact of centralization of prostate cancer surgery and radiotherapy services on the choice of prostate cancer treatment. PATIENTS AND METHODS: This national population-based study used linked cancer registry data and administrative hospital-level data for all 16 621 patients who were diagnosed between 1 January 2017 and 31 December 2018 with intermediate-risk prostate cancer and who underwent radical prostatectomy (RP) or radical radiation therapy (RT) in the English National Health Service (NHS). Travel times by car to treating centres were estimated using a geographic information system. We used logistic regression to assess the impact of the relative proximity of alternative treatment options on the type of treatment received, with adjustment for patient characteristics. RESULTS: Of the 78 NHS hospitals that provide RT or RP for prostate cancer, 41% provide both, 36% provide RT and 23% provide RP. Compared to patients who had both treatment options available at their nearest centre where overall 57% of patients received RT and 43% RP, patients were less likely to receive RT if their nearest centre offered RP only and the extra travel time to a hospital providing RT was >15 min (52% of patients received RT and 48% RP%, odds ratio [OR] 0.70 (0.58-0.85); P < 0.001). Conversely, patients were more likely to receive RT if their nearest centre offered RT and the extra travel time to a hospital providing RP was >15 min (63% of patients received RT and 37% RP, OR 1.23 (1.08-1.40); P < 0.001). There was a negligible impact on the type of treatment received if centres providing alternative treatment options were ≤15-min travel time from each other. CONCLUSION: The relative proximity of prostate cancer treatment options to a patient's residence is an independent predictor for the type of radical treatment received. Centralization policies for prostate cancer should not focus on one treatment modality but should consider all treatments to avoid a negative impact on treatment choice.

Outcomes following radical inguinal lymphadenectomy for penile cancer using a fascial-sparing surgical technique.

PURPOSE: To describe our surgical technique and report the oncological outcomes and complication rates using a fascial-sparing radical inguinal lymphadenectomy (RILND) technique for penile cancer patients with cN+ disease in the inguinal lymph nodes. METHODS: Over a 10-year period, 660 fascial-sparing RILND procedures were performed in 421 patients across two specialist penile cancer centres. The technique used a subinguinal incision with an ellipse of skin excised over any palpable nodes. Identification and preservation of the Scarpa's and Camper's fascia was the first step. All superficial inguinal nodes were removed en bloc under this fascial layer with preservation of the subcutaneous veins and fascia lata. The saphenous vein was spared where possible. Patient characteristics, oncologic outcomes and perioperative morbidity were retrospectively collected and analysed. Kaplan-Meier curves estimated the cancer-specific survival (CSS) functions after the procedure. RESULTS: Median (interquartile range, IQR) follow-up was 28 (14-90) months. A median (IQR) number of 8.0 (6.5-10.5) nodes were removed per groin. A total of 153 postoperative complications (36.1%) occurred, including 50 conservatively managed wound infections (11.9%), 21 cases of deep wound dehiscence (5.0%), 104 cases of lymphoedema (24.7%), 3 cases of deep vein thrombosis (0.7%), 1 case of pulmonary embolism (0.2%), and 1 case of postoperative sepsis (0.2%). The 3-year CSS was 86% (95%Confidence Interval [95% CI] 77-96), 83% (95% CI 72-92), 58% (95% CI 51-66), respectively, for the pN1, pN2 and pN3 patients (p < 0.001), compared to a 3-year CSS of 87% (95% CI 84-95) for the pN0 patients. CONCLUSION: Fascial-sparing RILND offers excellent oncological outcomes whilst decreasing the morbidity rates. Patients with more advanced nodal involvement had poorer survival rates, emphasizing the need for adjuvant chemo-radiotherapy.

High diagnostic accuracy of inguinal ultrasonography and fine-needle aspiration followed by dynamic sentinel lymph node biopsy in men with impalpable and palpable inguinal lymph nodes.

OBJECTIVES: To assess the accuracy of dynamic sentinel lymph node biopsy (DSNB) after negative ultrasonography (US) guided fine-needle aspiration (FNA) for inguinal lymph node (ILN) staging. PATIENTS AND METHODS: We performed a retrospective analysis of men with ≥T1G2 penile cancer and negative inguinal US-guided FNA undergoing DSNB. Men with suspicious US but negative FNA underwent US-guided ILN excision. Men with ≥T1G2 local recurrence during follow-up and non-squamous cell histologies were excluded. Descriptive analysis was performed, and sensitivity and negative predictive values (NPVs) were calculated. RESULTS: We included 403 men with 728 groins with negative FNA undergoing DSNB ± US-guided LN excision. At least one sentinel LN (SN) was visualised in 93% during the first and in 7% during the second lymphoscintigraphy. The median SNs visualised preoperatively was 1 SN and a median of 2 LNs were resected. ILN metastases were detected in 9% groins in men with impalpable and in 17% men with palpable LNs. Stratified by impalpable and palpable ILN, non-local recurrence despite pathologically negative DSNBs was seen in 0.5% and 0%, respectively. Limited to men with ≥24 months follow-up, non-local recurrence after negative DSNBs was seen in 0.4% and 0%, respectively. The sensitivity of DSNB was 96% and the NPV was 100%. The main limitation of this analysis is its retrospective nature with inherit biases. CONCLUSIONS: Inguinal US and FNA followed by DSNB can accurately stage men with both impalpable and palpable ILN, which provides logistical and surgical advantages.

Clinicopathological predictors of finding additional inguinal lymph node metastases in penile cancer patients after positive dynamic sentinel node biopsy: a European multicentre evaluation.

OBJECTIVE: To develop a predictive model for additional inguinal lymph node metastases (LNM) at inguinal lymph node dissection (ILND) after positive dynamic sentinel node biopsy (DSNB) using DSNB characteristics to identify a patient group in which ILND might be omitted. PATIENTS AND METHODS: We conducted a retrospective study of 407 inguinal basins with a positive DSNB in penile cancer patients who underwent subsequent ILND from seven European centres. From the histopathology reports, the number of positive and negative lymph nodes, presence of extranodal extension and size of the metastasis were recorded. Using bootstrapped logistic regression, variables were selected for the clinical prediction model based on the optimization of Akaike's information criterion. The area under the curve (AUC) of the receiver-operating characteristic curve was calculated for the resulting model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. RESULTS: Of the positive DSNBs, 64 (16%) harboured additional LNM at ILND. Number of positive nodes at positive DSNB (odds ratio [OR] 2.19, 95% confidence interval (CI) 1.17-4.00; P = 0.01) and largest metastasis size in mm (OR 1.06, 95% CI 1.03-1.10; P = 0.001) were selected for the clinical prediction model. The AUC was 0.67 (95% CI 0.60-0.74). The DCA showed no clinical benefit of using the clinical prediction model. CONCLUSION: A small but clinically important group of basins harbour additional LNM at completion ILND after positive DSNB. While DSNB characteristics were associated with additional LNM, they did not improve the selection of basins in which ILND could be omitted. Thus, completion ILND remains necessary in all basins with a positive DSNB.

Pelvic lymph node dissection alone versus adjuvant radiotherapy in node positive penile cancer: A systematic review.

Introduction: The management options for regional lymph nodes (LNs) in men with penile cancer include surveillance, surgery, and chemotherapy. The use of radiotherapy (RT) for nodal disease follows tradition and single-institution policies. We aimed to analyse the existing evidence regarding the management of penile cancer patients with suspected or known metastatic pelvic LNs using pelvic LN dissection (PLND) with RT versus PLND or RT alone. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with no filters for language or time. The search was conducted in EMBASE, MEDLINE/PubMed, and Cochrane Library. Inclusion criteria were adult men with penile cancer and suspected metastatic pelvic LNs, undergoing PLND with or without RT or RT alone. Primary outcomes included disease-specific survival and locoregional recurrence. Secondary outcomes included overall survival and complications of therapy. Results: A total of 552 articles were identified. Only eight retrospective studies were eligible for inclusion (including 406 patients). All studies had a high risk of bias. None of the studies reported the use of neoadjuvant RT. Indications for PLND varied but were usually two or more clinically positive inguinal nodes with or without extracapsular extension. Adjuvant RT was mainly used in positive pelvic LNs or pN2/pN3 stages. The rate of locoregional recurrence following adjuvant RT was 70%. Complications of treatment were reported in two studies only. Conclusions: There is insufficient evidence to recommend the use of adjuvant RT following PLND in penile cancer patients. The quality of evidence is low due to the retrospective design and high risk of bias. Randomized clinical trials are required to assess the efficacy and safety of adjuvant RT and PLND.

Radical Hemiscrotectomy and En Bloc Orchidectomy: Surgical Technique and Perioperative and Oncologic Outcomes of a Supra-Regional UK Referral Centre.

BACKGROUND AND PURPOSE: Hemiscrotectomy with en bloc orchidectomy represents a radical primary, completion, or salvage option in men with inguinoscrotal cancers. We describe our surgical technique and peri-operative and oncological outcomes. PATIENTS AND METHODS: Retrospective cohort study of 16 men treated at a supra-regional referral centre with open radical hemiscrotectomy with or without en bloc orchidectomy between 2010 and 2020. Peri-operative and survival outcomes were analysed. RESULTS: Radical hemiscrotectomy with or without en bloc orchidectomy was performed on 16 patients comprising 7 well-differentiated liposarcomas, 4 dedifferentiated liposarcomas, 2 leiomyosarcomas, 1 mesothelioma, 1 rhabdomyosarcoma and 1 mammary type myofibroblastoma. Primary hemiscrotectomy was performed in four, completion hemiscrotectomy in nine and salvage hemiscrotectomy in three. The median hospital stay was 2 days [interquartile range (IQR) 2-4]. Four patients (25%) had post-operative complications including wound infection or haematoma. During a median follow-up of 18 months (IQR 2-66), one patient (6%) died following a recurrence in the pelvis and retroperitoneum. DISCUSSION: and Conclusions If careful dissection is performed, radical hemiscrotectomy and en bloc orchidectomy is a radical but safe procedure with a short hospital stay. Haematoma and infection represent the main complications, and within limited follow-up most men showed no recurrence.

Predictors of local recurrence and its impact on survival after glansectomy for penile cancer: time to challenge the dogma?

OBJECTIVES: To identify predictive pathological factors for local recurrence (LR) and to study the impact of LR on survival in patients treated with glansectomy for penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS: We retrospectively studied patients treated with glansectomy at international, high-volume reference centres. We analysed histopathological predictors of LR, stratified patients into risk groups based on the number of risk factors present, and studied the impact of LR on survival outcomes using Kaplan-Meier survival analysis and stepwise Cox proportional hazards regression models. Subsequently, we performed sensitivity analyses excluding margin-positive cases, pT3 disease, and cN+ disease, or all of these factors. RESULTS: Across nine institutions, 897 patients were included, of whom 94 experienced LR. On multivariable analysis, presence of high-grade disease and pT3 stage were independent predictors of LR. LR-free survival rates significantly differed according to the number of risk factors present, with a hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.17-3.07; P = 0.01) for the intermediate-risk group (one risk factor) and 6.11 (95% CI 3.47-10.77; P < 0.001) for the high-risk group (two risk factors), using the low-risk group (no risk factors) as reference. Patients who experienced LR had significantly worse overall survival (OS; HR 2.89, 95% CI 2.02-4.14; P < 0.001) and cancer-specific survival (CSS; HR 5.64, 95% CI 3.45-9.22; P < 0.001). LR (HR 3.82, 95% CI 2.14-6.8; P < 0.001), lymphovascular invasion and cN status were significant predictors of decreased CSS. LR remained a strong predictor of both OS and CSS in all sensitivity analyses. CONCLUSIONS: Pathological T3 stage and presence of high-grade disease were independent histopathological predictors of LR after glansectomy for primary pSCC, which allowed risk stratification into three groups with significantly different risk of developing LR. Additionally, LR is related to poor OS and CSS, indicating that LR is a manifestation of underlying aggressive disease and clearly challenging the dogma of using organ-sparing surgery whenever possible since survival is unaffected by higher LR rates.

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols.

OBJECTIVE: To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. PATIENTS AND METHODS: This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien-Dindo grading system). RESULTS: In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien-Dindo Grade 1-2. CONCLUSIONS: DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

The treatment of penile carcinoma in situ (CIS) within a UK supra-regional network.

OBJECTIVES: To review outcomes of the treatment of carcinoma in situ (CIS) of the penis at a large supra-regional penile cancer network, where centralisation has permitted greater experience with treatment outcomes, and suggest treatment strategies. PATIENTS AND METHODS: The network penile cancer database, which details presentation, treatment and complications was analysed from 2003 to 2010, identifying patients with CIS, with a minimum follow-up of 2 years, looking at treatments administered and outcomes. RESULTS: In all, 57 patients with mean (range) age of 61 (34-91) years were identified. In all, 18 were treated by circumcision only, 20 by circumcision and local excision (LE) and 19 by circumcision and 5-flurouracil (5-FU). The mean (range) follow-up was 3.5 (2-8) years. Of those treated by circumcision none subsequently developed CIS on the glans. For those who underwent circumcision + LE, five of 20 (25%) developed recurrence requiring further treatment. Of those treated by circumcision + 5-FU, 14/19 (73.7%) completely responded. Of the five incomplete responders, two had focal invasive malignancy at repeat biopsy. One incomplete responder underwent glansectomy and four grafting. No complete responders relapsed. Complications of 5-FU included significant inflammatory response in seven (36.8%), with two requiring hospital admission and one neo-phimosis (5.3%). CONCLUSION: This study suggests that patients undergoing circumcision for isolated CIS and complete responders to 5-FU may require only short-term follow-up, as recurrence is unlikely, whereas longer follow up is required for all other patients. However, numbers in this study are small and larger studies are needed to support this. An incomplete response to 5-FU dictates immediate re-biopsy, as it carries a significant chance of previously undetected invasive disease.

Penile cancer treatment costs in England.

BACKGROUND: Penile cancer is a rare malignancy in Western countries, with an incidence rate of around 1 per 100,000. Due to its rarity, most treatment recommendations are based on small trials and case series reports. Furthermore, data on the resource implications are scarce. The objective of this study was to estimate the annual economic burden of treating penile cancer in England between 2006 and 2011 and the cost of treating a single case based on a modified version of the European Association of Urology penile cancer treatment guidelines. METHODS: A retrospective (non-comparative) case series was performed using data extracted from Hospital Episode Statistics. Patient admission data for invasive penile cancer or carcinoma in situ of the penis was extracted by ICD-10 code and matched to data from the 2010/11 National Tariff to calculate the mean number of patients and associated annual cost. A mathematical model was simultaneously developed to estimate mean treatment costs per patient based on interventions and their associated outcomes, advised under a modified version of the European Association of Urologists Treatment Guidelines. RESULTS: Approximately 640 patients per year received some form of inpatient care between 2006 and 2011, amounting to an average of 1,292 spells of care; with an average of 48 patients being treated in an outpatient setting. Mean annual costs per invasive penile cancer inpatient and outpatient were £3,737 and £1,051 respectively, with total mean annual costs amounting to £2,442,020 (excluding high cost drugs). The mean cost per case, including follow-up, was estimated to be £7,421 to £8,063. Results were sensitive to the setting in which care was delivered. CONCLUSIONS: The treatment of penile cancer consumes similar levels of resource to other urological cancers. This should be factored in to decisions concerning new treatment modalities as well as choices around resource allocation in specialist treatment centres and the value of preventative measures.

Should centralized histopathological review in penile cancer be the global standard?

OBJECTIVE: To assess the role of centralized pathological review in penile cancer management. MATERIALS AND METHODS: Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011. Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists. The biopsy specimens' histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology. Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management). RESULTS: A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England. After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management. When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found. CONCLUSIONS: In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management. The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer. In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the 'gold standard'.

The impact of transportation mode, socioeconomic deprivation and rurality on travel times to radiotherapy and surgical services for patients with prostate cancer: A national population-based evaluation.

BACKGROUND: The distances that patients have to travel can influence their access to cancer treatment. We investigated the determinants of travel time, separately for journeys by car and public transport, to centres providing radical surgery or radiotherapy for prostate cancer. METHODS: Using national cancer registry records linked to administrative hospital data, we identified patients who had radical surgery or radiotherapy for prostate cancer between January 2017 and December 2018 in the English National Health Service. Estimated travel times from the patients' residential area to the nearest specialist surgical or radiotherapy centre were estimated for journeys by car and by public transport. RESULTS: We included 13,186 men who had surgery and 26,581 who had radiotherapy. Estimated travel times by public transport (74.4 mins for surgery and 69.4 mins for radiotherapy) were more than twice as long as by car (33.4 mins and 29.1mins, respectively). Patients living in more socially deprived neighbourhoods in rural areas had the longest travel times to the nearest cancer treatment centres by car (62.0 mins for surgery and 52.1 mins for radiotherapy). Conversely patients living in more affluent neighbourhoods in urban conurbations had the shortest (18.7 mins for surgery and 17.9 mins for radiotherapy). CONCLUSION: Travel times to cancer centres vary widely according to mode of transport, socioeconomic deprivation, and rurality. Policies changing the geographical configuration of cancer services should consider the impact on the expected travel times both by car and by public transport to avoid enhancing existing inequalities in access to treatment and patient outcomes.

The Development and Feasibility of a Novel Electronic Patient-Reported Outcome Measures (Eproms) Questionnaire in patients with penile cancer.

BACKGROUND: Penile cancer (PeCa) is a rare cancer with surgical options that affect patients' quality-of-life. Patient-reported outcome measures (PROMs) are uncommonly utilized in this cohort despite their several patient-centered benefits and there are recommendations to further digitalize PROMs. This prospective, population-based study aimed to report the development and feasibility of a novel electronic patient-reported outcome measures (ePROMs) questionnaire for patients with PeCa. MATERIALS AND METHODS: A novel ePROMs questionnaire was developed and sent to patients 3 days before outpatient clinic appointments. The questionnaire included up to 30 items on patient symptomology and quality-of-life, including a self-reported quality-of-life score (rated 0 being worst and 100 being best). Data were collected for patients followed up between August 2021 and May 2022. The primary feasibility outcomes, adherence and engagement, were measured by response and drop-out rates. Differences in responders and nonresponders were also ascertained. Secondary outcomes explored the clinical utility of the questionnaire. Responders were subcategorized into 3 groups: circumcision (Ci), partial penectomy (PP) or total penectomy (TP) and differences were analyzed. This study was approved by the local Trust Governance Panel, including for ethical considerations. RESULTS: 220 adult males were sent ePROMs questionnaires, and 141 (64%) responded initially. The mean dropout rate of subsequent questionnaires was 56%. The maximum number of questionnaires sent to and completed by a patient was 8 (n = 1). Nonresponders were older (P < .0001), with poorer performance status (P < .0001) and lower body mass index (P = .0288). TP patients reported the lowest median quality-of-life score 68.50 (8-99), followed by the Ci group (72.0, 37-94) and the PP group (76.0, 10-99). CONCLUSIONS: Patients initially engaged and adhered to the ePROMs questionnaire but struggled to maintain this over time. Clinical data gathered by the questionnaire may be utilized to inform patient care. The questionnaire requires additional validation, research, and education.

A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

BACKGROUND: Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. METHODS: A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. DISCUSSION: There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. TRIAL REGISTRATION: Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.

Management of Lymph Node-positive Penile Cancer: A Systematic Review.

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.

Long-term trends in incidence, survival and mortality of primary penile cancer in England.

PURPOSE: Few population-based studies exist of long-term trends in penile cancer. We report incidence and mortality trends in England over the 31 years 1979-2009 and survival trends over the 40 years 1971-2010. METHODS: We calculated annual incidence and mortality rates per 100,000 by age and calendar period. We estimated incidence and mortality rate ratios for cohorts born since 1890, and one- and five-year relative survival (%) by age and deprivation category. RESULTS: A total of 9,690 men were diagnosed with penile cancer during 1979-2009. Age-standardized incidence rates increased by 21 %, from 1.10 to 1.33 per 100,000. Mortality rates fell by 20 % after 1994, from 0.39 to 0.31 per 100,000. Survival analyses included 11,478 men diagnosed during 1971-2010. Five-year relative survival increased from 61.4 to 70.2 %. Five-year survival for men diagnosed 2006-2010 was 77 % for men aged under 60 years and 53 % for men aged 80-99 years. The 8 % difference in five-year survival (66-74 %) between men in the most affluent and most deprived groups was not statistically significant. CONCLUSIONS: The 21 % increase in penile cancer incidence in England since the 1970s may be explained by changes in sexual practice, greater exposure to sexually transmitted oncogenic human papilloma viruses, and decreasing rates of childhood circumcision. Improvement in survival is likely due to advances in diagnostic, staging and surgical techniques. There is a need for public health education and potential preventative strategies to address the increasing incidence.

Prognostic Markers and Trials in Penile Cancer.

New tumor biomarkers open the potential for designing personalized therapy for penile squamous cell carcinoma. Despite the initial promising results of some biomarkers, controversy remains due to contradictory studies. Further robust research work is required before incorporating biomarkers in the personalized management of penile cancer. This narrative review aims to highlight some of the most commonly and recently investigated biomarkers of penile cancer and to summarize the ongoing registered clinical trials for the management of penile cancer patients.

Managing the cancer backlog: a national population-based study of patient mobility, waiting times and 'spare capacity' for cancer surgery.

Background: Waiting times for cancer treatments continue to increase in many countries. In this study we estimated potential 'spare surgical capacity' in the English NHS and identified regions more likely to have spare capacity based on patterns of patient mobility (the extent to which patients receive surgery at hospitals other than their nearest). Methods: We identified patients who had an elective breast or colorectal cancer surgical resection between January 2016 and December 2018. We estimated each hospital's 'maximum surgical capacity' as the maximum 6-month moving average of its surgical volume. 'Spare surgical capacity' was estimated as the difference between maximum surgical capacity and observed surgical volume. We assessed the association between spare surgical capacity and whether a hospital performed more or fewer procedures than expected due to patient mobility as well as the association between spare surgical capacity and whether or not waiting times targets for treatment were likely to be met. Findings: 100,585 and 49,445 patients underwent breast and colorectal cancer surgery respectively. 67 of 166 hospitals (40.4%) providing breast cancer surgery and 82 of 163 hospitals (50.3%) providing colorectal cancer surgery used less than 80% of their maximum surgical capacity. Hospitals with a 'net loss' of patients to hospitals further away had more potential spare capacity than hospitals with a 'net gain' of patients (p < 0.001 for breast and p = 0.01 for colorectal cancer). At the national level, we projected an annual potential spare capacity of 8389 breast cancer and 4262 colorectal cancer surgical procedures, approximately 25% of the volumes actually performed. Interpretation: Spare surgical capacity potentially exists in the present configuration of hospitals providing cancer surgery and requires regional allocation for efficient utilisation. Funding: National Institute for Health Research.

Corporal Skip Metastases in Penile Squamous Cell Carcinoma: An Unknown and Distinct Pattern of Spread with Poor Prognosis.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is characterised by stepwise lymphatic dissemination. Skip metastases (SkMs) are rare metastases in the corpus cavernosum or spongiosum without continuity to the primary tumour or its resection site. OBJECTIVE: To assess the distinct pattern of spread in SkM+ patients and the effect of SkM on prognosis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of patients with SkM+ PSCC at ten high-volume international referral centres between January 2006 and May 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated histopathological data, primary lymph node (LN) staging, and metastatic spread. We included a cohort of patients matched for pT stage, LN status, and grade who did not have SkM (SkM-) to compare the SkM prognosis and predictive value for cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Among the 63 SkM+ patients who met our inclusion criteria, the SkM diagnosis was synchronous in 54.0% and metastases were mostly located in the corpus cavernosum. SkM was symptomatic in 14% of cases, was detected on imaging in 32%, and was found incidentally on pathological examination in 27%. Fifty-one patients (81%) presented with positive LNs and 28 (44%) developed distant metastases. Seven patients (11%) presented with or developed distant metastasis without displaying any LN involvement. The 2-yr cancer-specific survival estimates were 36% (95% confidence interval [CI] 25-52%) for SkM+ and 66% (95% CI 55-80%) for matched SkM- patients (p < 0.001). On multivariable Cox regression analysis, SkM presence was an independent predictor for higher CSM (hazard ratio 2.05, 95% CI 1.06-4,12; p = 0.03). CONCLUSIONS: PSCC-related SkM is associated with aggressive disease behaviour and poor survival outcomes. Palpation of the entire penile shaft is essential, and distant staging is recommended in patients suspected of having SkM owing to the tendency for distant metastatic spread. PATIENT SUMMARY: We investigated outcomes for patients with cancer of the penis who had metastases in the tissues responsible for erection. We found that metastases in this location were associated with poor prognosis, even in the absence of more typical spread of cancer via the lymph nodes.