Detection Rate of 18F-Choline PET/CT and 68Ga-PSMA-HBED-CC PET/CT for Prostate Cancer Lymph Node Metastases with Direct Link from PET to Histopathology: Dependence on the Size of Tumor Deposits in Lymph Nodes

Abstract

Accurate detection of prostate cancer lymph node metastases (LNM) through PET/CT before lymphadenectomy is crucial for successful therapy. PET/CT with choline derivatives used to be the standard tool for imaging metastases, whereas ⁶⁸Ga-PSMA (prostate-specific membrane antigen) PET/CT was introduced recently. Both PET techniques were investigated with respect to what extent the detection rate of LNM depends on the size of tumor deposits (TDs) within LNM. Methods: Documenting the switch from the use of ¹⁸F-choline to ⁶⁸Ga-PSMA in 2014, we used 2 patient cohorts undergoing a template lymphadenectomy because of a PET/CT indicating LNM. Forty-four and 40 patients underwent PET/CT with ¹⁸F-choline or ⁶⁸Ga-PSMA ligand, respectively. In total, 226 LNM (125 ¹⁸F-choline, 101 ⁶⁸Ga-PSMA) originated from 73 salvage lymphadenectomies at biochemical recurrence and from 11 primary lymphadenectomies at radical prostatectomy. LNM eligible for direct correlation of PET/CT to histopathology were identified from lymphadenectomies conducted in small anatomic subregions, with 1 LNM (condition 1) or 1-2 LNM (condition 2). Longitudinal and short diameters of TD within LNM were determined by histopathology, allowing linking of the size of TD in LNM to the detection threshold of PET/CT. Diameters associated with a detection rate of 50% and 90% (d_50%, d_90%) were calculated on the basis of logistic growth curve models fitted. Results: Gleason score, number of removed LNs, and subregions for lymphadenectomy per patient did not differ significantly between the ¹⁸F-choline and ⁶⁸Ga-PSMA groups. The median prostate-specific antigen level at imaging and number of LNM per patient were significantly higher in the ¹⁸F-choline group (3.4 ng/mL, n = 34) than in the ⁶⁸Ga-PSMA group (2.2 ng/mL, n = 28; both P < 0.05). Longitudinal and short diameters of TD in LNM to reach d_90% were 11.2 and 7.4 mm, respectively, for ¹⁸F-choline PET/CT and 6.3 and 4.9 mm, respectively, for ⁶⁸Ga-PSMA PET/CT. Corresponding diameters to reach d_50% were 5.5 and 3.3 mm, respectively, for ¹⁸F-choline PET/CT and 3.7 and 2.3 mm, respectively, for ⁶⁸Ga-PSMA PET/CT. Detection rates were significantly higher under ⁶⁸Ga-PSMA (P = 0.005 and 0.04 for longitudinal and short diameter). Conclusion: ⁶⁸Ga-PSMA PET/CT is superior to ¹⁸F-choline PET/CT in the detection of LNM. Whether those results will lead to an improved patient outcome after ⁶⁸Ga-PSMA PET-guided therapy needs to be investigated by further studies.

Keywords: PSMA-PET/CT; choline-PET/CT; detection rate; lymph node metastases; prostate cancer.

FIGURE 1.

Workflow with surgery, tissue sample processing, and identification of eligible subregions in men with suspected nodal metastatic PCa undergoing a template lymphadenectomy after PET/CT. Tissue specimens from small anatomic subregions were removed separately at surgery. At histopathology, the size of TDs was determined. Aiming at a direct link from PET/CT to histopathology, subregions fulfilling the requirement for conditions 1 and 2 were selected from ¹⁸F-choline and the ⁶⁸Ga-PSMA PET/CT groups. Finally, size of TDs in detected and undetected LNMs was evaluated for estimation of detection thresholds.

FIGURE 2.

(A–D) Empiric detection rates from ¹⁸F-choline PET/CT and the ⁶⁸Ga-PSMA PET/CT groups for conditions 1 and 2 in dependence on diameter of TD (divided into intervals of 1 mm in length). Dark green line (condition 1) and light green line (condition 2) represent the fitted logistic growth curve model and red line the estimated diameters d_90% and d_50%, respectively. Longitudinal diameters (A and C) above 10 mm and short diameters (B and D) above 8 mm are shown as 1 group.

FIGURE 3.

Empiric detection rate for condition 1 (A and B) and 2 (C and D) in dependence on diameter of TD. Fitted logistic growth curve models for ¹⁸F-choline PET/CT and ⁶⁸Ga-PSMA PET/CT and P value for difference between the 2 curves are shown.