Evaluating survival in aggressive variant prostate cancer patients undergoing PSMA radioligand therapy.

259 Background: Aggressive variant prostate cancer (AVPC) is a subtype of metastatic castrate-resistant prostate cancer (mCRPC) characterized by several high-risk features. AVPC is associated with poorer overall survival and has limited response to androgen receptor targeted therapy, although it often shows some responsiveness to chemotherapy. In this study, we evaluated the outcomes of AVPC patients who received Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT). Methods: This retrospective study included 201 mCRPC patients who received Lutetium-177, [ 177 Lu]-PSMA RLT at two academic centers. Patients were classified as having AVPC based on the presence of at least one of the following eight criteria: exclusive visceral metastases (n=1), predominantly lytic bone metastasis (n=1), bulky lymphadenopathy or pelvic mass (≥5 cm) (n=4), low PSA (≤10 ng/mL) at initial presentation plus high-volume (≥20) bone metastases (n=0), serum CEA and/or LDH levels twice the upper limit of normal at the time of treatment (n=5), a short interval (≤6 months) to CRPC (n=7), small cell/neuroendocrine carcinoma morphology (n=5), and the presence of two or more genomic defects among TP53, RB1, and PTEN (n=13). Results: Of the 201 patients, 34 (16.9%) were classified as having AVPC (Table). The PSA50 response rate was 55% in the AVPC group and 60% in the non-AVPC group. The median overall survival (OS) (median time from the start of therapy to the last follow-up or death) was 171 days for the AVPC group and 282 days for the non-AVPC group. Although, the Kaplan-Meier plot only suggested a trend toward worse survival in AVPC patients compared to non-AVPC patients, the difference did not reach statistical significance (log-rank test p-value = 0.179). Conclusions: Our study suggests patients with AVPC may benefit from PSMA RLT and should be considered for this treatment if they are eligibly. Further studies are needed for a better understanding of this patient population. Details of patients. AVPC Non AVPC N=201 34 167 Age 1 (mean, year) 64.38 64.09 PSA 2 (mean, ng/mL) 331 251 PSA 3 (mean, ng/mL) 717 504 PSA50 (%) 55 60 OS/FU (median, day) 171 282 1 Age at the time of therapy. 2 Baseline PSA at diagnosis. 3 Most recent PSA prior to therapy.