Incremental value of ¹¹C-acetate over ⁶⁸Ga-PSMA PET/CT for diagnosis of primary prostate cancer patients with low-risk clinical factors

Objectives: ⁶⁸Ga-PSMA (prostate-specific membrane antigen) PET/CT has emerged in recent years with high clinical impact on prostate cancer (PCa) patients. This prospective study aims to evaluate the performance of ⁶⁸Ga-PSMA PET/CT in primary PCa diagnosis for patients with different pretest risks and to investigate whether ¹¹C-acetate PET/CT has an incremental value over ⁶⁸Ga-PSMA in any of the risk-stratified groups.

Methods: From Sep 2015 to Sep 2016, patients with biopsy-proven primary PCa referred to PET/CT for pretreatment staging were prospectively recruited. The patients were divided into low- and intermediate/high-risk groups. Intermediate/high-risk disease was defined as: 1. Gleason score (GS)=7 and serum PSA>=10 ng/mL; 2. GS>=8; or 3. PSA>20 ng/mL. Patients not satisfying these criteria were classified as low-risk. All patients underwent whole-body ¹¹C-acetate PET/CT at 20 min post-injection of 503±55 MBq ¹¹C-acetate, followed by whole-body ⁶⁸Ga-PSMA PET/CT at 60 min post-injection of 101±14 MBq ⁶⁸Ga-PSMA-HBED-CC. Reading of PET/CT studies were blinded to the biopsy results and assessment of primary prostate tumor involvement was on a lobar basis.

Results: 106 patients were evaluated, 30 of low-risk (age range: 45~86 years, mean=64.9±8.8 years) and 76 of intermediate/high-risk (age range: 46~88 years, mean=69.9±7.7 years). Biopsy results identified 17 unilobar and 13 bilobar PCa (43 PCa lobes) in low-risk group; 19 unilobar and 57 bilobar PCa (133 PCa lobes) in intermediate/high-risk group. Comparison on a lobar basis between ⁶⁸Ga-PSMA PET/CT and biopsy revealed a sensitivity and specificity of 53.5% (23/43) and 88.2% (15/17) in low-risk group, and respectively, 80.5% (107/133) and 89.5% (17/19) in intermediate/high-risk group, suggesting a strong correlation between PCa risk and detection sensitivity of PCa by ⁶⁸Ga-PSMA PET/CT. Combined use of ¹¹C-acetate PET/CT, however, detected 13/20 and 10/26 of the false negative lobes by ⁶⁸Ga-PSMA in low- and intermediate/high-risk groups, increasing the corresponding sensitivities to 83.7% (36/43) and 88.0% (117/133), respectively. The mean tumor SUV_max of ⁶⁸Ga-PSMA was significantly lower in low-risk group than that in intermediate/high-risk group (8.5±5.1 vs. 24.4±20.5, P<0.001), suggesting that ⁶⁸Ga-PSMA binding avidity correlated with PCa risk; however, there is no significant difference in mean tumor SUV_max of ¹¹C-acetate between the 2 risk groups (4.3±1.0 vs. 5.1±2.5, P>0.05).

Conclusion: Besides from recurrence and metastatic survey, ⁶⁸Ga-PSMA PET/CT was also found to have reasonable accuracy for primary tumor diagnosis in newly diagnosed PCa. The likelihood and confidence for ⁶⁸Ga-PSMA PET/CT to localize PCa lesions were found to increase with clinical PCa risk, better than ¹¹C-acetate. However, the inclusion of ¹¹C-acetate PET/CT has a significant incremental value to ⁶⁸Ga-PSMA in the low-risk patients because for those in this group who are reluctant for biopsy, additional of ¹¹C-acetate data may enhance their decision making to obtain tissue confirmation. Research Support: Hong Kong Sanatorium & Hospital