Craniocaudal nodal length (CCNL) as a risk-factor for relapse in stage I non-seminomatous germ cell tumors (NSGCT).
Authors: McHugh Deaglan Joseph , Fernandes Maria Clara , Funt Samuel Aaron , Bromberg Maria , Knezevic Andrea , Nikolovski Ines , Feldman Darren R. 
Published: June 2022

e17011

Background: Lymphovascular invasion and embryonal carcinoma predominant (ECP) subtype are the only consistent factors predictive of relapse on active surveillance (AS) in Stage I NSGCT. Current practice guidelines define stage I disease by axial dimensions only, despite routine coronal reformations of axial CT images permitting CCNL measurement. CCNL was previously reported to be associated with increased risk of relapse in stage I NSGCT, independent of other risk factors (Howard et al, 2014). We sought to validate this finding through time-to-event (TTE) analyses in a larger, independent cohort. Methods: Patients with NSGCT who had undergone orchiectomy between 2/1/10 and 10/31/2017 and had baseline CT imaging performed within 90 days of orchiectomy were included. CCNL was measured using the largest lymph node by axial dimensions, with nodal morphological descriptors recorded. Median CCNL (17mm) was rounded to the nearest 5mm (15mm) and dichotomized into <15mm or > 15mm, deemed the most clinically translatable landmark. TTE was a composite of either relapse on AS, a positive primary retroperitoneal lymph node dissection (PRPLND), or relapse after negative PRPLND. TTE was estimated using Kaplan-Meier method, with time calculated from date of orchiectomy to date of event or censoring at last follow-up. Results: 134 stage I NSGCT patients were included, 64 (48%) with stage IA and 70 (52%) with stage IB. Median age at diagnosis was 30 years (range 18 to 34). ECP histology was seen in 82 (61%) patients. Median CCNL was 17mm (range 5 to 34) and 71 patients (53%) had a CCNL > 15mm. Presence of fatty hilum and suspicious morphology were observed in 86 (66%) and 11 patients (8%) respectively. CCNL did not differ by stage at diagnosis (Wilcoxon p = 0.26) or ECP histology (Wilcoxon p = 0.95). PRPLND was performed in 7 of 64 stage IA (11%) and 45 of 70 stage IB (64%) patients. Twenty-six patients relapsed on AS, 9 had positive PRPLND histology and 3 with a negative PRPLND later relapsed. All 38 events occurred in the first year after orchiectomy except for relapse on AS in three stage IA patients at 1.2, 2.8 and 4.0 years. Median follow-up time is 5.0 years (range 1.5 months to 10 years). The one-year event-free rate was 72.7% (95% CI: 64.0, 79.6). TTE differed significantly by stage at diagnosis and did not differ significantly by ECP histology, CCNL (> 15mm versus ≤15mm), presence of fatty hilum, or presence of suspicious morphology (all p > 0.05). In a stratified analysis, event rate did not differ by CCNL > 15mm versus ≤15mm within stage IA or IB patients (p = 0.58 and 0.60, respectively). Conclusions: Using TTE analyses in a larger, contemporary patient cohort, CCLN was not associated with increased risk of relapse in stage I NSGCT and does not lend support to its addition to staging or risk prediction models. The association between CCNL and relapse risk in stage I seminoma is currently being analyzed.