Circulating tumor DNA as a prognostic biomarker to predict retroperitoneal histology in patients undergoing retroperitoneal lymph node dissection.

Abstract

646 Background: Serum tumor markers (STM) are used in the management of patients with testicular cancer. However, a proportion have normal STM even with cancer present. Circulating tumor DNA (ctDNA) has shown promise in for detection of persistent disease. We sought to determine the utility of ctDNA for predicting retroperitoneal histology by comparing patients’ retroperitoneal lymph node dissection (RPLND) histology with their pre-operative ctDNA status. Methods: Patients undergoing primary (P-RPLND) or post-chemotherapy (PC-RPLND) from March 2023 to January 2024 had prospectively collected plasma ctDNA assay (Signatera, Natera Inc.) The association between ctDNA and RPLND histology was assessed. Sensitivity (SN), specificity (SP), and positive (PPV) and negative predictive values (NPV) were calculated for ctDNA to detect active cancer or teratoma alone in the RPLND histology. Results: Forty-six patients undergoing RPLND had pre-operative ctDNA collection with a median age of 33.5 (IQR:27-38.8). Plasma was collected on average, 8.6 days pre-operatively. Twenty (43.5%) patients underwent P-RPLND and 26 (56.5%) patients underwent PC-RPLND. ctDNA was positive in 23 (50%) patients. Two patients underwent P-RPLND for stage I disease and both had (-) ctDNA and histology. Eighteen patients underwent P-RPLND for stage II disease. Of these, 16 had active cancer, 1 had pure teratoma, and 1 had negative histology. ctDNA was positive in 15 of these patients all of which were found to have either teratoma or active cancer on pathology. Of the 3 patients with (-) ctDNA, 1 had negative histology, 1 had mixed, teratoma and seminoma, and 1 had pure seminoma. There were 26 patients who had ctDNA drawn prior to PC-RPLND. Of these, 4 had active cancer, 16 had pure teratoma, and 6 had necrosis on final RPLND histology. ctDNA was positive in 8 patients all of whom had either teratoma or active cancer on histology. Of the 18 PC-RPLND patients with a (-) ctDNA test, 1 had active cancer, 11 had teratoma, and 6 had necrosis. There were no false positive tests in the entire cohort. The SN, SP, PPV, and NPV were 85%, 77%, 74%, 87%, respectively for predicting active cancer. These numbers vary by primary or PC-RPLND patients (Table). Conclusions: To our knowledge, this is the first study evaluating test characteristics of ctDNA results in relation to RPLND histology. These findings suggest that ctDNA may be a useful adjunctive screening tool to predict active cancer or teratoma in the RP. Test characteristics of ctDNA stratified by primary or post-chemotherapy RPLND. Sensitivity Specificity PPV NPV P-RPLND GCT and/or Teratoma 88% 100% 100% 60% GCT only 88% 75% 93% 60% Teratoma only 100% 26% 7% 100% PC-RPLND GCT and/or teratoma 40% 100% 100% 33% GCT only 75% 77% 38% 94% Teratoma only 31% 70% 63% 39%