Introduction:

Circulating tumor DNA (ctDNA) has been gaining popularity in directing and tailoring treatment modalities in solid cancers. ctDNA utility before and after diagnosis of testicular cancer has not yet been well-characterized. We seek to characterize the utility of ctDNA in correlation with pathologic and clinical features in patients with testicular cancer who underwent retroperitoneal lymph node dissection (RPLND).

Methods:

Our single institution prospectively maintained database identified consecutive patients who underwent radical orchiectomy for germ cell tumor (GCT) between 2021 - 2023, included were patients who had prospectively collected ctDNA (Signatera^TM) analyses performed before and after RPLND. ctDNA signature was informed from the radical orchiectomy specimen in 9 patients and from the RPLND specimen in 8 patients (Figure 1). The informed signature was used throughout the patient’s surveillance. Pre-RPLND ctDNA status was determined from blood drawn prior to surgery, and the post-RPLND minimal residual disease (MRD) window ctDNA status was determined from blood drawn after and within 90 days from RPLND. Study findings were reported using descriptive statistics. R programming language version 4.3.1 was used for all statistical analyses.

Results:

Seventeen patients had 89 ctDNA analyses performed before and after RPLND. The median age was 31 (IQR 25-33). The median follow-up time was 11 months (IQR 7-13). The primary testicular pathology prior to RPLND was non-seminoma for 14 patients (82.3%), seminoma for 2 patients (11.7%), and one patient had primary retroperitoneal seminoma (5.8%). Nine patients underwent primary RPLND (53%), 6 underwent post-chemotherapy RPLND (PS-RPLND, 35%) and 2 patients had RPLND performed due to recurrence while on surveillance for clinical stage I (11.7%). Serum tumor markers (STM) were normal for all the patients prior to RPLND. Pre-RPLND ctDNA status was available for 13 patients, ctDNA was undetectable in 8 patients (5 had benign pathology and 3 had teratoma), and detectable in 5 patients (38%); among them, 4 had viable GCT and one had teratoma. Fourteen patients had ctDNA MRD window status available. Four had detectable ctDNA status (28.5), all of them had disease progression (100%) and received further chemotherapy after RPLND. Only 1 of the 4 patients had elevated STM after RPLND (25%). Ten patients (71.4%) had undetectable MRD ctDNA status, 9 patients (90%) are currently under surveillance without evidence of disease recurrence, and one patient received adjuvant chemotherapy after RPLND without evidence of disease recurrence, all had post-RPLND normal STM.  Detectable pre-RPLND ctDNA signature was found only in 1 of 4 patients with teratoma on RPLND histology (25%).

Conclusion:

Detectable ctDNA status in the pre-RPLND status was associated with viable GCT on histology while having normal STM. Undetectable pre-RPLND ctDNA was associated with either no tumor or teratoma on histology. Detectable ctDNA status at the MRD window was associated with disease progression in all patients while only 25% had elevated STM. While preliminary, ctDNA status may be used in the future to inform both urologists and oncologists when tailoring treatment protocols to patients with negative/mildly elevated serum tumor markers and for treatment escalation/de-escalation. Prospective studies with larger cohorts are necessary to validate these initial results.

Funding: N/A