Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study

Abstract

Introduction: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown.

Materials & methods: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([^99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed.

Results: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients.

Conclusions: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.

Keywords: Lymph node dissection; Lymph node metastases; Prostate cancer; Prostate-specific membrane antigen; Radioguided surgery; Staging.

Fig. 1

[⁶⁸Ga]Ga-PSMA-11 PET/MRI scan identified a suspicious lymph node at the level of the left obturatory region, as shown in PET (a), MRI (b) and PET/MRI (c) axial view

Fig. 2

[⁹⁹mTc]Tc-PSMA-I&S SPECT/CT scan identified a suspicious lymph node at the level of the left obturatory region, as shown in SPECT (a), CT (b) and SPECT/CT (c) axial view

Fig. 3

Real-time intraoperative use of the Drop-In gamma probe (Crystal Drop-In Probe; Crystal Photonics, Berlin, Germany) for in vivo measurements at the level of the right external iliac region during PSMA-RGS

Fig. 4

Distribution of maximum diameter of nodal metastasis stratified according to PSMA-RGS positivity based on TtB ratio ≥ 2