Patterns of Recurrence following Inguinal Lymph Node Dissection for Penile Cancer: Optimizing Surveillance Strategies

Abstract

Purpose:Our primary objective is to detail the incidence, site, and timing of penile squamous cell carcinoma (pSCC) recurrence after inguinal lymph node dissection (ILND).Materials and Methods:We performed a retrospective analysis of 551 patients who underwent ILND for pSCC from 2000 to 2017. The primary outcome was pSCC recurrence after ILND. Recurrences were identified and stratified by site. Timing of recurrence was determined. Multivariable logistic regression analysis determined associations with recurrence. Multivariable Cox regression analysis determined associations with overall survival (OS). Sub-group analysis of the distant recurrences analyzed timing and OS by site of distant recurrence.Results:After ILND pSCC recurred in 176 (31.9%) patients. Median time to recurrence was 10 months for distant recurrences, 12 for inguinal, 10.5 for pelvic, and 44.5 for local. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months of ILND, versus 127 months for local recurrences. Post-ILND recurrence was associated with pN2 (OR 1.99, 95% CI 1.0–4.1), and pN3 (OR 7.2, 95% CI 4.0–13.7). Patients who had local recurrence had similar OS to those without (HR 1.5, 95% CI 0.6–3.8), and worse OS was identified in patients with inguinal (HR 4.5, 95% CI 2.8–7.1), pelvic (HR 2.6, 95% CI 1.5–4.5), or distant (HR 4.0, 95% CI 2.7–5.8) recurrences. Patients with lung recurrences had worse OS than other sites (HR 2.2, 95% CI 1.1–4.3).Conclusions:Of the patients 31.9% had post-ILND recurrence associated with high pN staging. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months, suggesting surveillance beyond this is low yield. Local recurrences occurred over a longer timeline, emphasizing necessity of long-term surveillance of the primary site.

Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer

“…The recurrence rate after pelvic treatment (61%) in this study is, as expected with more advanced disease, much higher than after inguinal LN dissection (ILND; 31%), as reported by Chakiryan et al [17] . Likewise, the number of distant recurrences as a fraction of the total number of recurrences is higher after pelvic treatment (64%) than after ILND (46%) [8] .…”

“…Likewise, the number of distant recurrences as a fraction of the total number of recurrences is higher after pelvic treatment (64%) than after ILND (46%) [8] . The time to recurrence was also shorter after pelvic treatment (97% of recurrences within 24 mo) than after ILND (95% of recurrences within 48 mo) [17] .…”

Concomitant vs Staged Therapeutic Inguinal Lymphadenectomy in Clinically Node Positive Penile Squamous Cell Carcinoma: Does It Make a Difference?

“…Efforts to reduce the morbidity of penile cancer treatment with penile-sparing surgery and modified and minimally invasive ILNDs show success 15,23 but have not translated to improved survival in men with lymph node positive penile cancer in the past 2 decades. 24,25 Compared to men without pathological evidence of disease in the groin, men with pathological nodal metastases fare poorly with higher likelihood of distance recurrence and cancer-related mortality 2 regardless of the timing of ILND. 26 With demonstration of improved RFS and OS after neoadjuvant regimens such as paclitaxel/ifosfamide/cisplatin 27 in men with bulky inguinal adenopathy, the paradigm has shifted toward the integration of NAC with or without radiotherapy followed by consolidative ILND.…”

“…The extent of inguinal lymph node metastases has been identified as the factor most predictive of prognosis in penile cancer patients. 1,2 However, the optimal approach to local and systemic management of metastatic penile cancer in inguinal lymph nodes remains unclear. While both the National Comprehensive Cancer Network and European Association of Urology guidelines recommend pathological staging of palpable inguinal lymph nodes with biopsy, excision, or inguinal lymph node dissection (ILND), 3,4 factors driving the completion and timing of ILND in real-world clinical scenarios are nuanced.…”

Innovative systemic therapies for penile cancer

“…Pathology review of PSCC tissue is an essential initial diagnostic step as it will determine the need for inguinal lymph node dissection for patients without clinical lymph node enlargement [4 & ,5]. Recent data has shown a potential additional role of the detection of the HPV infection in better determining the need for an inguinal lymph node dissection (ILND) [6 ]. Requirement for the strongest prognostic marker for PSCC patients remains the evaluation of regional nodal involvement [7 & ] as the risk of disease recurrence and mortality for these patients best correlates with the extent of lymph node extension at the time of diagnosis [8 & ].…”