Despite complete resection, 20%-50% of patients with localized renal cell carcinoma (RCC) experience recurrence within 5 years. Accurate assessment of prognosis in high-risk patients would aid in improving outcomes. Here we evaluate the use of circulating tumor DNA (ctDNA) in RCC using banked samples and clinical data from a single institution.
The cohort consisted of 45 RCC patients (≥pT1b) who underwent complete resection. The presence of ctDNA in plasma was determined using a personalized, tumor-informed ctDNA assay (Signatera RUO, Natera, Inc.). Relationships with outcomes and other relevant clinical variables were assessed. The median follow-up was 62 months.
Plasma ctDNA was detected in 18 out of 36 patients (50%) pre-operatively and was associated with increased tumor size (mean 9.3 cm vs. 7.0 cm, P < .05) and high Fuhrman grade (60% grades III-IV vs 27% grade II, P = .07). The presence of ctDNA, either pre-operatively or at any time post-operatively, was associated with inferior relapse-free survival (HR = 2.70, P = .046; HR = 3.23, P = .003, respectively). Among patients who were ctDNA positive at any time point, the sensitivity of relapse prediction was 84% with a PPV of 90%. Of note, ctDNA positivity at a post-surgical time point revealed a PPV of 100% and NPV of 64%. The lack of ctDNA detection at both time points yielded an NPV of 80%.
Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies.
The oncologist. 2024 Jul 16 [Epub ahead of print]
Andres F Correa, Ekaterina Kalashnikova, Hsin-Ta Wu, Ryan M Winters, Mustafa Balcioglu, Sumedha Sudhaman, Denise C Connolly, Yulan Gong, Robert G Uzzo, Himanshu Sethi, Adam C ElNaggar, Alexey Aleshin, Minetta C Liu, Philip H Abbosh
Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, United States., Natera, Inc., Novato, CA, United States., Biosample Repository Facility, Fox Chase Cancer Center, Philadelphia, PA, United States., Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, United States., Nuclear Dynamics and Cancer, Fox Chase Cancer Center, Philadelphia, PA, United States.