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.

Lymphovascular and perineural invasion are risk factors for inguinal lymph node metastases in men with T1G2 penile cancer.

PURPOSE: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. METHODS: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. RESULTS: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6-11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6-9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99-1.04, p = 0.17). CONCLUSION: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

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.

Treatment Options and Outcomes for Men with Penile Intraepithelial Neoplasia: A Systematic Review.

Penile intraepithelial neoplasia (PeIN) is a rare skin condition with potential to progress to invasive penile cancer. We performed a systematic review of treatment options and outcomes for PeIN. Topical agents showed response and recurrence rates of 40-100% and 20% for imiquimod, and 48-74% and 11% for 5-fluorouracil, respectively. Discontinuation of topical agents because of side effects was observed in 12% of cases. Response rates for laser therapies were 52-100%, with recurrence in 7-48% of cases and a change in penile sensitivity in 50%. Circumcision cleared preputial PeIN. Rates of recurrence after surgical treatment of glans PeIN were 25% for wide local excision, 4% for Mohs surgery, 5% for total glans resurfacing, and 10% for glansectomy. There are limited data on factors predictive of treatment response and on sequencing of treatment options. PATIENT SUMMARY: Several treatment options are available for men with precancerous lesions of the foreskin or glans. Close follow-up is necessary as lesions can recur or progress to invasive penile cancer.

Saphenous-sparing Ascending Video Endoscopic Inguinal Lymph Node Dissection Using a Leg Approach: Surgical Technique and Perioperative and Pathological Outcomes.

BACKGROUND: Open inguinal lymph node dissection (oILND) has high morbidity. Ascending saphenous-sparing video endoscopic ILND (VEILND-AS+) represents a minimally invasive alternative with potential benefits. OBJECTIVE: To describe our VEILND-AS+ technique and compare outcomes to oILND. DESIGN SETTING AND PARTICIPANTS: This was a retrospective cohort study of penile cancer patients. SURGICAL PROCEDURE: VEILND-AS+ was performed according to the technique described in the supplementary video. MEASUREMENTS: We compared perioperative and pathological outcomes between the two procedures. RESULTS AND LIMITATIONS: In the study cohort of 206 men we performed 40 VEILND-AS+ and 251 oILND procedures. In comparison to oILND, VEILND-AS+ had a longer operation time (185 vs 120 min; p < 0.01) but a shorter hospital stay (2 vs 4 d; p < 0.01). A median of eight resected lymph nodes with a median of one affected node per groin was observed in both groups. Extranodal extension was found in 30% of cases after VEILND-AS+ and 35% after oILND. In both groups the median drainage time was 13 d. Wound infections were observed in 38% of cases after VEILND-AS+ and 27% after oILND (p = 0.19). Skin necrosis or wound breakdown occurred in 0% and 6% of cases after VEILND-AS+ and oILND (p < 0.01), while lymphoceles were drained in 18% and 7% of cases, respectively(p = 0.03). Following VEILND-AS+ and oILND, 20% and 14% of patients, respectively, were referred to a lymph oedema clinic (p < 0.01). CONCLUSIONS: VEILND-AS+ is a safe procedure and offers shorter hospital stays and possibly a lower risk of skin necrosis and wound breakdown in comparison to oILND. Further improvements in the VEILND-AS+ technique are required to reduce complications associated with dead space and injury to lymphatic vessels. PATIENT SUMMARY: For patients undergoing surgery on lymph nodes in the groin, a minimally invasive approach instead of open surgery led to discharge 2 days earlier and may have lower rates of severe wound complications.

Practice Patterns Among Penile Cancer Surgeons Performing Dynamic Sentinel Lymph Node Biopsy and Radical Inguinal Lymph Node Dissection in Men with Penile Cancer: A eUROGEN Survey.

Dynamic sentinel lymph node biopsy (DSNB) and radical inguinal lymph node dissection (ILND) are important in the management of penile cancer patients, but high-level evidence for preoperative, perioperative, and postoperative management remains scarce. According to an online survey of 35 surgeons from ten European countries, 57% perform >10 ILND procedures per year and 86% offer DSNB. Furthermore, management differs substantially for dye injection site, use of lymphoscintigraphy, preferred incision sites, techniques for lymphatic control, duration of empiric antibiotic therapy, perioperative thromboprophylaxis, time points for drain removal, and definition of the ILND dissection floor. Consensus was observed for the use of perioperative antibiotics (although not duration and type) and the borders for ILND template definitions. We conclude that there is significant variation in patient management among eUROGEN penile cancer surgeons. This heterogeneity may confound multicentre studies; therefore, a consensus to standardise inguinal node management in penile cancer across European penile cancer centres is warranted. PATIENT SUMMARY: Our survey reveals that preferences and surgical techniques for inguinal lymph node sampling and removal varies significantly between European penile cancer surgeons. Consensus is needed to standardise the management approach for penile cancer.

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.

Clinicopathological characteristics and outcomes in men with mesothelioma of the tunica vaginalis testis: analysis of published case-series data.

PURPOSE: Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor, and currently, there are no published treatment recommendations. METHODS: We performed a systematic literature review and synthesized clinical presentation, clinicopathological factors associated with metastatic disease, treatment options, and outcomes in men with MTVT. RESULTS: We included 170 publications providing data on 275 patients. Metastatic disease occurred in 84/275 (31%) men with malignant MTVT: Most common sites included retroperitoneal lymph nodes (LNs) (40/84, 48%), lungs (30/84, 36%), and inguinal LNs (23/84, 27%). Invasion of the spermatic cord or scrotum was the only risk factor for local recurrence [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.36-7.57]. Metastatic disease was associated with age ≥ 42 years (OR 3.02, 95% CI 1.33-6.86), tumor size ≥ 49 mm (OR 6.17, 95% CI 1.84-20.74), presence of necrosis (OR 8.31, 95% CI 1.58-43.62), high mitotic index (OR 13.36, 95% CI 1.53-116.51) or angiolymphatic invasion (OR 3.75, 95% CI 1.02-13.80), and local recurrence (OR 4.35, 95% CI 2.00-9.44). Complete remission in the metastatic setting was observed in five patients, most of whom were treated with multimodal therapy. Median survival in patients with metastatic disease was 18 months (IQR 7-43). CONCLUSION: Malignant MTVT is a rare but aggressive disease. Since local recurrence is a risk factor for metastatic progression, we recommend aggressive local treatment. Survival and response to any treatment in the metastatic setting are limited.