Introduction:

Prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging has enhanced both staging and detection of recurrence for prostate cancer. However, anatomic recurrence patterns for surgically resectable high-risk disease with regional node involvement on PSMA-PET remain poorly defined. Improved understanding of recurrence patterns can allow for optimization of adjuvant treatment and surveillance strategies. We sought to characterize radiographic recurrence patterns of patients with high-risk prostate cancer who underwent PSMA-PET imaging followed by radical prostatectomy (RP) with pelvic lymph node dissection (PLND) and had pathologic nodal involvement (pN1) at surgery.

Methods:

We retrospectively identified patients with pN1 disease who underwent RP/PLND for localized or locoregional high-risk prostate cancer at a tertiary referral center from 2021 to 2024. Each patient had pre-operative PSMA-PET imaging; those with distant metastases were excluded. Time to radiographic recurrence and location of the most distant radiographic recurrence were recorded. Radiographic recurrence location was categorized as periprostatic, pelvic lymph nodes (either within or outside of extended PLND template), or distant (including non-regional lymph nodes, bone or visceral recurrences).  Patients were classified by their most distant site of recurrence. We evaluated for association between nodal involvement on pre-operative PSMA-PET (cN1) and presence of 1.) any radiographic recurrence and 2.) distant radiographic recurrence using multivariable and univariable Cox proportional hazards models, respectively.

Results:

There were 79 patients with surgically resectable NCCN high-risk disease, pre-operative PSMA-PET imaging, and pN1 status at RP/PLND. Of these, 24 were cN1 on pre-operative PSMA-PET (sensitivity 30%; 95% CI: 21 - 42%). Median follow up was 7 months (IQR 4-13 mo.) among those who remained free of radiographic recurrence. There were 33 patients who developed radiographic recurrence, including 16 with distant recurrence. Figure 1 depicts the anatomic distribution of the most distant radiographic recurrence site. The 1-year adjusted probability of any radiographic recurrence was 28% (95% CI: 9 - 43%) in cN0 disease and 77% (95% CI: 37 - 87%) in cN1 disease (Figure 2). There was a significant association between cN1 status on pre-operative PSMA-PET and any radiographic recurrence (HR 4.23; 95% CI: 1.86 - 9.58; p<0.001) as well as distant radiographic recurrence (HR 5.81; 95% CI: 1.79 - 18.8; p=0.002).

Conclusion:

Clinical node involvement on pre-operative PSMA-PET is significantly associated with radiographic recurrence for patients with pN1 status following RP/PLND. The high risk of recurrence in these patients supports offering upfront treatment intensification and counseling on the likely need for salvage therapy. Additionally, recurrence within the PLND field was common, highlighting the limitations of current surgical approaches in achieving oncologic control for this high-risk group.

Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers at MSKCC and NIH/NCI grants P30CA008748 and P50CA092629