Correlation of ⁶⁸Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer

Abstract

Rationale: ⁶⁸Ga-RM2 targets gastrin-releasing peptide receptors (GRPR), which are overexpressed in prostate cancer (PC). Here, we compared pre-operative ⁶⁸Ga-RM2 PET to post-surgery histopathology in patients with newly diagnosed intermediate- or high-risk PC. Methods: Forty-one men, 64.0+/-6.7-year-old, were prospectively enrolled. PET images were acquired 42 – 72 (median+/-SD 52.5+/-6.5) minutes after injection of 118.4 – 247.9 (median+/-SD 138.0+/-22.2)MBq of ⁶⁸Ga-RM2. PET findings were compared to pre-operative mpMRI (n = 36) and ⁶⁸Ga-PSMA11 PET (n = 17) and correlated to post-prostatectomy whole-mount histopathology (n = 32) and time to biochemical recurrence. Nine participants decided to undergo radiation therapy after study enrollment. Results: All participants had intermediate (n = 17) or high-risk (n = 24) PC and were scheduled for prostatectomy. Prostate specific antigen (PSA) was 8.8+/-77.4 (range 2.5 – 504) ng/mL, and 7.6+/-5.3 (range 2.5 – 28.0) ng/mL when excluding participants who ultimately underwent radiation treatment. Pre-operative ⁶⁸Ga-RM2 PET identified 70 intraprostatic foci of uptake in 40/41 patients. Post-prostatectomy histopathology was available in 32 patients in which ⁶⁸Ga-RM2 PET identified 50/54 intraprostatic lesions (detection rate = 93%). ⁶⁸Ga-RM2 uptake was recorded in 19 non-enlarged pelvic lymph nodes in 6 patients. Pathology confirmed lymph node metastases in 16 lesions, and follow-up imaging confirmed nodal metastases in 2 lesions. ⁶⁸Ga-PSMA11 and ⁶⁸Ga-RM2 PET identified 27 and 26 intraprostatic lesions, respectively, and 5 pelvic lymph nodes each in 17 patients. Concordance between ⁶⁸Ga-RM2 and ⁶⁸Ga-PSMA11 PET was found in 18 prostatic lesions in 11 patients, and 4 lymph nodes in 2 patients. Non-congruent findings were observed in 6 patients (intraprostatic lesions in 4 patients and nodal lesions in 2 patients). Both ⁶⁸Ga-RM2 and ⁶⁸Ga-PSMA11 had higher sensitivity and accuracy rates with 98%, 89%, and 95%, 89%, respectively, compared to mpMRI at 77% and 77%. Specificity was highest for mpMRI with 75% followed by ⁶⁸Ga-PSMA11 (67%), and ⁶⁸Ga-RM2 (65%). Conclusion: ⁶⁸Ga-RM2 PET accurately detects intermediate- and high-risk primary PC with a detection rate of 93%. In addition, it showed significantly higher specificity and accuracy compared to mpMRI and similar performance to ⁶⁸Ga-PSMA11 PET. These findings need to be confirmed in larger studies to identify which patients will benefit from one or the other or both radiopharmaceuticals.