We compared the efficacy of mpMRI and 18F-DCFPyL PET/CT for the detection of recurrent PCa lesions in patients who were treated with LDR brachytherapy and subsequently experienced biochemical failure. In our study, overall positivity rates were similar among the two modalities for intraprostatic and seminal vesicle lesions, however, biopsy and histopathology analysis revealed a higher PPV for 18F-DCFPyL PET/CT. Additionally, 18F-DCFPyL PET/CT had a higher positivity rate for the detection of pelvic and extra-pelvic lymph nodes than mpMRI, which can be attributed to a greater dependence on size criteria (>1cm) in evaluation of lymph nodes by mpMRI and the limited coverage of MRI compared to PET/CT.
There are limited studies in the literature evaluating or comparing these two imaging modalities in patients with recurrence after LDR brachytherapy. Unlike other treatment modalities, LDR brachytherapy results in a substantial degree of artifact from the numerous permanently implanted brachytherapy seeds within the prostate. Although these seeds can result in mild CT scatter, they substantially impact the quality of MRI. In several studies, PET/CT was found to perform better than mpMRI for the identification extraprostatic disease. In one recent study, Liu et al demonstrated that 18F-DCFPyL PET revealed extraprostatic cancer foci in twice as many men with radio-recurrent prostate cancer compared with conventional imaging, which included pelvic MRIs. 18F-DCFPyL PET detected intraprostatic recurrence in 87% of men compared with 67% with MRI. However, this study included multiple types of radiation therapy including EBRT and brachytherapy; moreover there was no histopathologic validation for the intraprostatic foci suspicious for recurrence (26).
mpMRI has played a large and increasing role in localized prostate cancer management over the past couple of decades due to its ability to provide exceptional anatomic detail. However, in patients who have undergone LDR brachytherapy, the diagnosis of local recurrence on mpMRI is challenging secondary to the susceptibility artifacts related to implanted seeds and therapeutic glandular changes (i.e. decrease in glandular size and diffusely heterogeneous prostatic signal intensity pattern in MRI) (15, 27). This is reflected in the relatively poor performance of mpMRI in this study which demonstrated an intraprostatic PPV of only 71.43%Biopsy results revealed cancer in 2 lesions which were MRI(-) and benign tissue in 2 out of 9 mpMRI(+) lesions which lowered the PPV.
In contrast, PET/CT is a molecular imaging study which relies less on anatomic features and more on cellular biology and is thus less impacted by seed implantation. For intraprostatic lesions, 18F-DCFPyL PET/CT had a PPV of 87.5%. This reflects the lower rate of false positives associated with PET/CT compared to mpMRI. The finding of one false negative lesion on 18F-DCFPyL PET/CT, a bladder wall lesion, speaks to the high sensitivity of this imaging technique. Lesions near the bladder wall may be more challenging to detect given the urinary excretion of the radiotracer.
Multiple studies have confirmed a high detection rate of recurrent PCa with various PSMA-targeting radiotracers even in biochemical recurrence patients with low PSA levels, and usually exceeds mpMRI (28-30). Some studies suggest a strong correlation between PSA levels and diagnostic performance of PSMA-targeting PET tracers (28-32). Our small sample size cohort did not allow for such a correlation, however in a future study with a larger cohort, imaging results should be correlated with PSA levels to test whether this holds true in patients who have undergone brachytherapy.
Previous studies have commented on the benefit of combined use of mpMRI and PSMA PET/CT for more accurate diagnosis of foci of local recurrence after radical prostatectomy or primary radiotherapy (12, 33, 34). In our cohort, we observed a similar benefit. While MRI was able to deliver high resolution anatomic scans, PSMA PET/CT illustrated cancer specific uptake. This combination resulted in a radiologic diagnosis of recurrence in most of our patients. An important advantage of PSMA PET/CT was the higher positivity rate to identify lymph node involvement. The finding of disease in extraprostatic sites changes the potential treatments appropriate for the patient.
Biochemical recurrence after radiation therapy has been traditionally managed by use of conventional staging and imaging methods such as computed tomography and bone scan with subsequent initiation of androgen deprivation therapy (35). Use of more novel and dedicated imaging techniques such as mpMRI combined with PSMA PET/CT has been documented to better depict and map the disease burden in prostate cancer patients with BCR (36). This robust imaging approach can also aid delivering personalized salvage treatment instead of standalone systematic androgen deprivation. Few groups have reported promising results on utility of using PSMA PET/CT guided salvage radiation therapy for patients with BCR (37, 38). Although we did not perform a formal analysis, several of the patients included in our study were found to have isolated local recurrence and were found to be eligible to enroll on trials of salvage local therapy.
There are several limitations to this study. First, thorough statistical methods were impossible with the small study population, but relevant clinical analysis was performed. Secondly, there was a lack of uniformity in the treatment history of our cohort, with 8/15 patients receiving both brachytherapy and EBRT. Additionally, not all patients had corresponding biopsy results, and lymph nodes were not biopsied uniformly. Lymph node biopsy can often be challenging in this setting given the proximity to critical structures, lack of enlargement of the suspected lymph node, and the confines of the bony pelvis. Additionally, biopsy was not performed if the results would not affect disease management. The findings could also be confounded by the referral bias. Salvage systemic treatment is usually commenced early in patients with rapid PSA doubling time after onset of biochemical failure as these patients have a higher predilection for distant metastasis (39, 40). No patient in this study was on ADT at the time of imaging, therefore, it is likely that the majority of our patients had relatively slower PSA kinetics which could affect the preponderance of local failure in our study. Finally, all imaging data were interpreted by experts with significant experience in mpMRI and PSMA PET which could limit the reproducibility of results in other centers.
In conclusion, we demonstrate that 18F-DCFPyL PET/CT may be superior to mpMRI for identifying sites of recurrence in patients with suspected PCa recurrence after LDR brachytherapy with or without external beam radiotherapy. Further studies with larger patient populations and more robust histopathological sampling are necessary to validate our findings.