Primary Penile Cancer: The Role of Adjuvant Radiation Therapy in the Management of Extranodal Extension in Lymph Nodes

Abstract

Background: In head and neck cancer, the presence of extranodal extension (ENE) in lymph nodes (LNs) has been shown prospectively to require adding chemotherapy to postoperative radiation therapy (RT). Limited data exist regarding ENE in LNs from primary penile cancer (PeCa). Objective: To determine the association of RT and ENE in PeCa. Design, setting, and participants: We retrospectively analyzed the outcomes of 93 patients with pT1-4 N3 M0 (American Joint Committee on Cancer 7th edition) squamous cell carcinoma of the penis across four international centers. Intervention: If the inguinal nodal specimen had ENE or two or more positive inguinal LNs, RT was delivered to an ipsilateral inguinal field. An ipsilateral pelvic field was added for positive pelvic LNs on dissection. The delivered dose was usually 50 Gy in 25 daily fractions. Outcome measurements and statistical analysis: Clinical and demographic characteristics of relapse-free (RFS), disease-specific (DSS), and overall (OS) survival were compared by ENE status and receipt of adjuvant RT. Results and limitations: Seventy-two percent of patients had inguinal ENE, and 49% had pelvic ENE. On multivariable analysis (MVA) of ENE-negative patients, an OS benefit was noted with postoperative chemotherapy (p = 0.038) and inguinopelvic RT (p = 0.037). RFS suffered with worsening grade of the lesion (moderately: p = 0.027; poorly: p = 0.038), but was improved with groin (p = 0.016) and inguinopelvic (p = 0.006) RT. On MVA of patients with ENE, inguinopelvic RT was associated with better DSS (p = 0.041). Grade impacted DSS (moderately: p = 0.043; poorly: p = 0.033), and poorly differentiated lesions impacted RFS (p = 0.013). Conclusions: Inguinopelvic RT may benefit regional control in PeCa patients with positive pelvic LNs, but this appears to be limited to those without ENE. Patient summary: For patients with penile cancer and positive pelvic lymph nodes, postoperative radiation therapy was found to decrease the likelihood of disease recurrence in the groin or pelvis only if extranodal extension was absent.

Management of Advanced Penile Cancer

“…Radiotherapy with concurrent chemotherapy has become a standard management strategy for head and neck, vulvar, and anal squamous cancers, [56][57][58] but its use in the perioperative setting in penile cancer is limited by the small number of available studies. 59 The EAU penile cancer guideline group recently conducted a systematic review of the evidence and concluded that because of the heterogeneous and limited evidence of clinical benefit, a routine recommendation of adjuvant radiotherapy is not yet warranted. 60 In conclusion, the current standard of care is founded on limited data but remains as neoadjuvant chemotherapy with TIP as the preferred regimen, followed by surgical treatment.…”

Impact of radiation therapy on perineal urethrostomy for penile cancer

“…Secondly, adjuvant therapies are infrequently used as a rule in PeCa: only in about one of seven cases in our review. This is because the limited data reveals only a potential role for RT in selected primary lesions [2] and in pN3 patients [4] , [5] .…”

Recent advances in the management of penile cancer

“…Currently, the use of radiotherapy for nodal metastases is not recommended 33 . However, emerging research suggests that radiotherapy can improve regional control in PC patients with involved pelvic lymph nodes 34 without extranodal extension 35 .…”