INVESTIGATING PATTERNS OF PROSTATE CANCER RECURRENCE FOLLOWING BRACHYTHERAPY USING PSMA-PET ANALYSIS

Purpose:

Radiation therapies such as external beam radiation therapy (EBRT) and brachytherapy (BT) are mainstays of localized prostate cancer (PCa) management. The ASCENDE-RT trial demonstrated an extension in the biochemical progression-free survival of patients with intermediate- to high-risk prostate cancer that received a BT boost alongside androgen deprivation therapy (ADT)+EBRT compared to those that received ADT+EBRT alone (83% versus 62%), highlighting the synergistic impact of these multiparametric treatments. However, the patterns of recurrence after brachytherapy remain largely unknown. Additionally, the growing role of functional radioimaging using prostate specific membrane antigen (PSMA) positron emission tomography (PET) is radically improving our sensitivity for detection of small volumes of disease at local, regional, and metastatic sites.

Materials and Methods:

This prospective cohort study characterizes the locations, times-to-progression, and disease burden of local, regional, and distant recurrent disease using PSMA-PET imaging. A total of 153 patients who received either BT monotherapy (n=116) or EBRT+BT boost (n=36) and underwent PSMA-PET imaging after experiencing biochemical failure were analyzed. The differences between groups subanalyzed by Gleason score and time-to-progression were tested using Mann-Whitney U and chi-square tests.

Results:

The rates of cancer recurrence in the prostate were lower following boosted therapy than monotherapy (22.2% versus 48.3%, p<0.05), with reduced recurrence in the prostate base and proportionally greater recurrence in the middle and apex. Boosted therapies were less likely to develop in-field recurrence at the seminal vesicles compared to monotherapies for all groups except low-grade cancers, where the rate of recurrence was comparable. Cancers treated with monotherapy were more likely to develop single node recurrence (44.8% versus 6.67%, p<0.05), whereas boosted therapies were more likely to recur in multiple nodes by the time of PET imaging (60.0% versus 34.5%, p<0.05). Furthermore, whereas the distribution and likelihood of nodal recurrence following monotherapy was similar for early and late recurrences of low- and high-grade cancers, boosted therapies had markedly different distribution patterns depending on the times-to-progression and initial disease stage. Finally, analysis of bony metastases shows that earlier recurrences are more likely to be outside of the pelvis and vertebrae than later recurrences (84.6% versus 37.5%, p<0.05), with boosted therapies leading to greater out-of-field metastases than monotherapies (64.6% versus 41.2%, p<0.05).

Conclusions:

In total, this improves our understanding of treatment response to prostate brachytherapies. It highlights how patterns of recurrence can vary dramatically depending on initial treatment, cancer staging, and time-to-progression, which emphasizes how the ability of PSMA-PET to localize even microscopic recurrence can help determine optimal post-treatment strategies for residual disease.