Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

Altered tumor microenvironment heterogeneity of penile cancer during progression from non-lymphatic to lymphatic metastasis.

BACKGROUND: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. METHODS: In this study, using single-cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. RESULTS: The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial-mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. CONCLUSIONS: This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non-lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Quality of Life Evaluation after Partial Penile Amputation for Penile Cancer.

BACKGROUND: Penile cancer is most prevalent in developing countries. Both the physiological and psychological consequences for the patient are critical. These consequences result from both the cancer diagnosis and the treatment's effects. OBJECTIVE: The objective of this study was to evaluate the quality of life (QoL) of patients who have undergone partial penile amputation in terms of general well-being, sexual function, and urinary function. MATERIALS AND METHODS: This retrospective observational study included 32 patients who underwent partial penile amputation. The european organisation for research and treatment of cancer core quality of life questionnaire (EORTC QLQ C-30) questionnaire was completed postoperatively. Erectile function and satisfaction were assessed retrospectively after partial penile amputation using the International Index of Erectile Function-15. RESULTS: The mean age of the patients was 54.03 ± 16.02 years. The mean scores for erectile function, orgasm, sexual desire, satisfaction, and overall satisfaction were 16.28 ± 10.83, 7.50 ± 3.30, 5.72 ± 3.35, 8.84 ± 4.77, and 9.12 ± 0.83 preoperatively, and 14.03 ± 8.61, 6.88 ± 2.97, 5.72 ± 3.35, 7.94 ± 4.09, and 7.81 ± 1.00 postoperatively. Mean erectile function, orgasm, satisfaction, and overall satisfaction were significantly decreased postoperatively compared with preoperatively. Erectile function and overall satisfaction improved more in younger years from the preoperative to the postoperative period, whereas they improved less in older years. CONCLUSION: Although partial penile amputation for penile cancer provides adequate local disease management, appropriate counseling is crucial, especially when the QoL concerns general well-being, sexual function, and urinary function.

Résumé Contexte:Le cancer du pénis est plus répandu dans les pays en développement. Les conséquences physiologiques et psychologiques pour le patient sont cruciales. Ces conséquences résultent à la fois du diagnostic de cancer et des effets du traitement.Objectif:L'objectif de cette étude était d'évaluer la qualité de vie (QdV) des patients ayant subi une amputation partielle du pénis en termes de bien­être général, de fonction sexuelle et de fonction urinaire.Matériels et méthodes:Cette étude observationnelle rétrospective a inclus 32 patients ayant subi une amputation partielle du pénis. Le questionnaire de base sur la qualité de vie de l'organisation européenne pour la recherche et le traitement du cancer (EORTC QLQ C­30) a été complété en postopératoire. La fonction érectile et la satisfaction ont été évaluées rétrospectivement après une amputation partielle du pénis à l'aide de l'indice international de la fonction érectile­15.Résultats:L'âge moyen des patients était de 54,03 ± 16,02 ans. Les scores moyens pour la fonction érectile, l'orgasme, le désir sexuel, la satisfaction et la satisfaction globale étaient de 16,28 ± 10,83, 7,50 ± 3,30, 5,72 ± 3,35, 8,84 ± 4,77 et 9,12 ± 0,83 en préopératoire, et de 14,03 ± 8,61, 6,88 ± 2,97, 5,72. ± 3,35, 7,94 ± 4,09 et 7,81 ± 1,00 en postopératoire. La fonction érectile moyenne, l'orgasme, la satisfaction et la satisfaction globale étaient significativement diminués en postopératoire par rapport au préopératoire. La fonction érectile et la satisfaction globale se sont améliorées davantage dans les années plus jeunes, de la période préopératoire à la période postopératoire, alors qu'elles se sont moins améliorées dans les années plus âgées.Conclusion:Bien que l'amputation partielle du pénis pour le cancer du pénis permette une prise en charge locale adéquate de la maladie, un conseil approprié est crucial, en particulier lorsque la qualité de vie concerne le bien­être général, la fonction sexuelle et la fonction urinaire.

Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen.

INTRODUCTION: Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC-A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. METHODS: Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC-A measurements in 2014-2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC-A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. RESULTS: Eighty patients were included. LCGM models identified two distinct trajectories of SCC-A: low-stable (40%; n = 32) and high-decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23-10.53], p = 0.019), progression-free survival (HR [95% CI]: 11.33 [3.19-40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high-decline arm. CONCLUSION: PC patients' SCC-A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC-A might assist tumor monitoring after systemic therapies.

Psychosocial Impact of Penile Cancer: An Unmet Need.

Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation.

Next-generation sequencing of primary testicular lymphoma and relapse in the glans penis after prophylactic radiation therapy: a rare case report.

BACKGROUND: Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse. CASE PRESENTATION: A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens. CONCLUSIONS: We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis.

Management of Bulky Inguinal and Pelvic Lymph Nodes.

Penile cancer with bulky inguinal metastasis has a high probability of harboring pathologically involved lymph nodes best managed in a multidisciplinary care setting. Appropriate staging with cross-sectional imaging and fine-needle aspirate cytology of suspicious nodes guide decision-making for the use of platinum-based neoadjuvant chemotherapy followed by inguinal lymph node dissection. Surgical resection plays an important diagnostic, therapeutic, and guiding role in disease management. Patients with adverse pathologic features, especially those with extranodal disease extension, may derive additional benefit from adjuvant radiotherapy.

New Therapeutic Horizons for Advanced or Metastatic Penile Cancer.

Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates are low. Studies combining ICIs with both chemotherapy and targeted therapy are ongoing. Up to 50% of penile cancer cases are associated with human papillomavirus (HPV). HPV-targeting therapies, such as HPV-targeting vaccines and T-cell receptor therapies, are an area of active investigation. Penile cancer cells also express cell surface antigens that may be targeted by the emerging class of antibody-drug conjugates.

Pathology of Squamous Cell Carcinoma of the Penis: Back to Square One.

The landscape of squamous cell carcinoma of the penis (SCC-P) has undergone a significant transformation since the new World Health Organization classification of genitourinary cancers and recent European Association of Urology/American Association of Clinical Oncology guidelines. These changes emphasize the necessity to categorize SCC-P into 2 groups based on its association with human papillomavirus (HPV) infection. This shift has major implications, considering that prior knowledge was derived from a mix of both groups. Given the distinct prognosis, treatment options, and staging systems observed for HPV-associated tumors in other body areas, the question now arises: will similar patterns emerge for SCC-P?

Overview of Systemic Therapies in Penile Cancer.

Penile cancer (PC), although rare, poses significant challenges in both diagnosis and treatment. Penile squamous cell carcinoma (PSCC) represents the most common histologic subtype of PC, accounting for approximately 95% of cases. With limited therapeutic options available, systemic therapies have emerged as critical components in the management of advanced PSCC. Recent developments in clinical research have revealed the effectiveness of new therapeutic strategies. By elucidating the mechanism of action and clinical evidence supporting these treatments, we strive to offer insights into optimizing treatment strategies and enhancing the quality of care for patients affected by this complex disease.

Immune-based Therapies for Penile Cancer.

This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing on immunotherapy, vaccine therapy, and cell-based treatments, especially in the context of human papillomavirus-related PSCC. Factors influencing these therapies are discussed. These include the immune microenvironment, programmed cell death ligand-1 expression, and tumor immune cell infiltration. This article also highlights immune checkpoint inhibitors and related clinical trials. This review supports the use of personalized medicine in treating PSCC. It stresses the need for collaborative studies and data sharing to create specific treatment plans and achieve better outcomes.

Robot-assisted inguinal lymphadenectomy to treat penile and vulvar cancers: a scoping review.

INTRODUCTION: Inguinal lymph nodes dissection (ILND) is recommended in patients presenting with high-risk penile (PC) or vulvar cancers (VC). Though, this surgical procedure is underused because of its anticipated morbidity. Minimally invasive approaches were proposed to minimize complications associated with open surgery. In this review, we analyze current available data exploring intra and perioperative outcomes of robot-assisted ILND (RAIL). EVIDENCE ACQUISITION: On April 9th, 2023, a literature search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: ("robotic assisted" OR "robot-assisted" OR "robotic") AND ("inguinal lymph node dissection" OR "lymphadenectomy") AND ("penile cancer" OR "vulvar cancer"). Out of the 404 identified articles, 18 were used for the present scoping review and their results were reported according to the PRISMA statement. EVIDENCE SYNTHESIS: Data on 171 patients, ranging in age from 32 to 85 years, were obtained. Most of them (90.6%) harbored a penile squamous cell carcinoma and presented with no palpable nodes (85%). Operation time (OT) ranged between 45 and 300 min. Estimated blood loss varied from 10 to 300 mL. One single intra-operative complication was reported and one conversion to open was recorded. The lymph nodes (LNs) count spanned from 3 to 26 per groin, with 17 studies reporting a median yield >7 nodes. Hospital stay was 1-7 days, while the duration of drainage ranged from 4 to 72 days. Post-operative complications included lymphocele (22.2%; 0-100%), lymphedema (13.4%; 0-40%), cellulitis (11.1%; 0-25%), skin necrosis (8.7%; 0-15.4%). seroma (3.5%; 0-20%) and wound breakdown/wound infection (2.9%; 0-10%). Out of the included studies, 7 provided at least a 12-month follow-up, with recurrence-free rates ranging from 50% to 100% in patients affected by penile cancer and from 92% to 100% in vulvar cancer patients. CONCLUSIONS: The available evidence on RAIL for the treatment of PC and VC is limited. The approach appears to be safe and effective, as it provides an adequate lymph node yield while ensuring a minimally morbid postoperative course and a short hospital stay.

Clinicopathological and Molecular Features of Penile Melanoma With a Proposed Staging System.

Penile melanomas (PM) are an exceedingly rare subtype of mucosal melanoma (MM), and we reviewed the clinicopathologic features and molecular profile in 8 PMs. The patient ages ranged from 46 to 78 (mean: 62.8) years with involvement on the glans (n=5; 62.5%), penile urethra (n=2; 25%), and foreskin (n=1, 12.5%). Tumor depth ranged from 1.6 to 10.0 (mean: 5.25) mm. Most of the patients underwent partial penectomy (n=6; 75%) and sentinel lymph node (LN) biopsy N=7; 87.5%). Seven patients had metastatic disease at diagnosis, 6 involving LNs and 1 the adrenal gland, and 4 died of disease with a mean follow-up period of 40.5 (2 to 95) months. Five of 7 (71%) cases identified 15 molecular alterations within KIT , CDKN2A , NF1 , PTEN , and APC (n=2 each), and NRAS , MAP3K1 , CDH1 , MSH6 , and TERT (n=1 each). Two cases were not found to harbor genetic aberrations, and 1 case failed testing. In addition, we reviewed the English literature and included 93 cases with a reported depth of invasion and follow-up. A total of 101 PMs were analyzed for prognostic parameters, and the overall survival was significantly worse in patients with LN metastasis (P=0.0008), distant metastasis (P=0.0016), and greater depth of invasion (P=0.0222) based upon T-stage. While T4 conferred substantially worse survival, the delineation of the survival curves between T2 and T3 was less clear, and combining T2+T3 disease had a strong prognostic impact ( P =0.0024). Prognostic parameters used in the staging of cutaneous melanomas may also be used in PMs. An alternative staging system expanding the inclusion criteria for T2 might provide a more accurate prognostic stratification.

Cyclin D1 expression in penile cancer.

The main goal of the present study was to analyze the expression profile of cyclin D1 in patients with PC, and to determine possible correlations with clinical and histopathological features. A survey was conducted with 100 patients diagnosed with PC, who were treated at two reference hospitals in São Luís, Maranhão, Brazil, between 2013 and 2017. A review of clinical, epidemiological, and histopathological data was performed, Human Papillomavírus (HPV) DNA was detected using polymerase chain reaction (PCR) and cyclin D1 expression analysis was performed using immunohistochemical techniques. The data revealed that the absence of cyclin D1 expression was significantly associated with HPV-positive histological subtypes (p = 0.001), while its expression was associated with high-grade tumors (p = 0.014), histological subtype (p = 0.001), presence of sarcomatoid transformation (p = 0.04), and perineural invasion (p = 0.023). Patients with cyclin D1 expression exhibited lower disease-free survival compared to the cyclin D1-negative group, although the difference was not statistically significant. The results suggest that cyclin D1 may be a potential biomarker for PC, especially for poorer prognosis.

Enhanced Prognostic Factors for Disease-Free Survival in Penile Squamous Cell Carcinoma: Insights From Songklanagarind Hospital.

OBJECTIVE: This study aimed to investigate disease-free survival (DFS) outcomes and associated prognostic factors among surgically treated penile cancer patients at Songklanagarind Hospital, Thailand, over a 20-year period. METHODS: A retrospective analysis was conducted on 208 primary penile cancer patients treated between January 2001 and December 2022. Disease-free survival was assessed using Kaplan-Meier survival curves, and Cox proportional hazard models were employed for multivariate analysis. RESULTS: All of patients (100%) were squamous cell carcinoma of penis, with 38.9% having T1 tumors, 70.7% well-differentiated tumors, and 32.6% diagnosed at stage III. The recurrence rate was 16.8%, with a mean time to recurrence of 25.9 months. Disease-free survival rates at 1, 3, and 5 years were 82.1%, 72%, and 70.2%, respectively. Median overall survival was 18.2 months, with rates at 1, 3, and 5 years at 68.7%, 44.7%, and 36.4%, respectively. Significant associations were found between disease-free survival and higher T stage, clinical chronic inflammation, delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that higher primary tumor stage (T) was the only independent prognostic factor for disease-free survival. CONCLUSION: This study provides valuable insights into disease-free survival outcomes in penile cancer treatment at a single institution over an extended period. Higher pathologic T stage emerged as the sole independent prognostic factor for disease-free survival. Further validation through large-scale prospective studies is warranted.