RESUMEN
BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.
Asunto(s)
Radioisótopos de Galio , Neoplasias de la Próstata , Masculino , Humanos , Adolescente , Adulto , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/terapia , Tomografía de Emisión de Positrones/métodos , Antígeno Prostático Específico , Imagen por Resonancia MagnéticaRESUMEN
Prostate-specific membrane antigen (PSMA) PET offers an accuracy superior to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in the primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients before initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was performed in men with a new diagnosis of intermediate- or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 y. We examined the Kendall correlation between PET (intense uptake in the primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan-Meier analysis. Results: Seventy-three men (age, 64.0 ± 6.3 y) were imaged. Seventy-two had focal uptake in the prostate, and in 20 (27%) PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patient positivity than nodal dissection in patients with only 5-15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in the primary lesion (SUVmax > 12.5, P = 0.008) and presence of PSMA metastasis (P = 0.013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2 y (4.93 and 3.95, respectively) were similar to or higher than other clinicopathologic prognostic factors. Conclusion: 68Ga-PSMA-11 PET can risk-stratify patients with intermediate- or high-grade prostate cancer before prostatectomy based on degree of uptake in the prostate and presence of metastatic disease.