In the diagnosis setting, preliminary studies have shown that the merging of mpMRI with 68Ga-PSMA PET can allow for the biological characterization of lesions identified in mpMRI. In a study by Eiber at al, 53 patients with localized prostate cancer were studied in a 68Ga-PSMA integrated PET/mpMRI unit prior to prostatectomy. On correlation with the pathological specimen, the sensitivity for PET/mpMRI was superior to mpMRI alone (98% vs. 66%) in diagnosis of prostate cancer but no correlation was found between PET intensity and Gleason score. In regards to staging, 68Ga-PSMA has been reported to clearly improve detection of lymph node metastases compared to conventional morphological imaging (MRI or CT). In a pooled meta-analysis assessing 223 patients the sensitivity for detection of lymph node metastases by 68Ga-PSMA was 61% with a specificity of 97%. The introduction of these imaging techniques into clinical practice will likely cause a stage migration towards advanced disease, with a significant number of previously thought to have localized prostate cancer being diagnosed with low volume nodal or distant oligo-metastatic disease. The treatment of these patients remains controversial with some small retrospective series advocating for aggressive local management while others support systemic treatment. There are several ongoing trials (NCT02971358 and NCT03298087) assessing the best treatment plan for this patient cohort thus all efforts should be made to treat these patients in trials.
Treatment of localized prostate cancer provides a cure for a significant number of patients, but approximately 15-40% of these patients will experience a recurrence in the form of a PSA elevation known as biochemical recurrence (BCR). The management of recurrences can be tricky as they are hard to characterize with conventional imaging which usually leads to some form of overtreatment. PSMA-directed compounds have been increasingly studied and validated in the recurrence setting. In a meta-analysis by von Eyben et al, which pooled 983 patients, 68Ga-PSMA was found to have a sensitivity of 88% for recurrence detection, at median PSA of 2.3 ng/mL. Importantly, the sensitivity of 68Ga-PSMA is dependent on PSA, with 50% sensitivity and 97% specificity in identifying recurrences in patients presenting with PSA values ranging between 0.2 to 0.5 ng/mL. As with staging, use of these novel PET agents will increase the diagnosis of low volume recurrences, prompting the use of recurrence directed local therapies (surgery and radiation). While multiple reports have shown that metastatic directed therapy is safe, the oncological benefit of these interventions remains to be validated.
The role of 68Ga-PSMA-PET in the management of patients with large volume or hormone refractory metastatic prostate cancer remains to be defined. While the higher sensitivity of PSMA tracers may be appealing for assessing disease response; one possible confounding factor is the increased expression of the PSMA protein associated with anti-androgen therapy in prostate cancer cell lines and animal models.
A new and exciting application of the 68Ga-PSMA ligands is their linking with beta emitters (90Y and 177Lu), for targeted treatment of metastatic foci. In a phase 1 trial using 177Lu-PSMA in 56 patients with CRPC, the targeted therapy was found to have a low side-effect profile with 56% of the patients achieving a partial response.
In summary, 68Ga-PSMA radio-ligands have shown promise in the early diagnosis, staging, detection of post-treatment recurrence. Their use in patients with metastatic disease remains to be defined and at this time is not recommended outside of clinical trials. Lastly, PSMA ligands are now being introduced as a theranostic treatment with their merging with beta emitters.
Presented by: Robert E. Reiter MD, Professor of Urology and Director JCCC Genitourinary Oncology Program at University of California Los Angeles (UCLA)
Written by: Andres F. Correa, Society of Urologic Oncology Fellow, Fox Chase Cancer Center-Temple Health, Philadelphia, PA at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC