Prognostic significance of a negative PSMA PET/CT in biochemical recurrence of prostate cancer

Abstract

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming standard of care for men with biochemical recurrence (BCR) of prostate cancer. The implications of a negative PSMA PET/CT scan in this population remain unclear. This study aims to assess the outcome of patients with BCR post radical prostatectomy (RP) who have negative [¹⁸F]DCFPyL PET/CT scan at relapse.

Methods: This is a post-hoc subgroup analysis of a prospective non randomized clinical trial. One hundred and one patients (median age, 75 years) with BCR after RP, who tested negative on [¹⁸F]DCFPyL PET/CT and subsequently either underwent salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) or were followed without active treatment, were included. Freedom from progression (FFP) after negative PSMA PET/CT was determined based on follow-up imaging selected as per clinical practice. Uni- and multivariate Cox regression analyses were performed to examine the association of patients' characteristics, tumor-specific variables, and treatment with clinical progression at the last follow-up. FFP at 1-, 2-, and 3-year were reported using Kaplan Meier analysis.

Results: The median PSA level at PET/CT was 0.56 ng/mL (range, 0.4-11.3). Sixty five (64%) patients were followed without receiving further treatment, and 36 (36%) received sRT (18% to the prostate bed only and 18% to the prostate bed and pelvic lymph nodes) within 3 months of the PSMA PET. Seventeen of the sRT patients (17 of 36, 47%) received concomitant androgen deprivation therapy (ADT). Median follow-up was 39 months. Subsequent clinical progression was detected in 21 patients (21%), with 52% in pelvic lymph nodes, 52% in the prostatic fossa, 19% in distant lymph nodes, 14% in lungs, and 10% in bones. The FFP was 95% (95% CI: 91%-99%) at 12 months, 87% (95% CI: 81%-94%) at 24 months, and 79% (95% CI: 71%-88%) at 36 months. Multivariate Cox regression analysis revealed that an initial International Society of Urological Pathology (ISUP) grade 5 was significantly associated with clinical progression at the last follow-up (hazard ratio, 5.1, P value, 0.04). Furthermore, the receipt of sRT correlated significantly with lower clinical progression at the last follow-up (hazard ratio, 0.2, P value, 0.03), whereas other clinical and tumor-specific parameters did not. Following surveillance-only and sRT, 29% (19 of 65) and 6% (2 of 36) of patients, respectively, showed clinical progression. In the sRT group, no significant difference was observed in FFP between patients who underwent sRT to the prostatic fossa versus those who received sRT to the prostatic fossa and pelvic lymph nodes, although the numbers in these groups were small.

Conclusions: This study suggests that salvage radiotherapy is associated with a decreased or delayed clinical progression in patients with biochemical recurrence following radical prostatectomy who have negative PSMA PET/CT scan results. The analysis also underscores the prognostic significance of the initial ISUP grade, with ISUP grade 5 being associated with worse outcomes.

Trial registration: Registered September 14, 2016; NCT02899312 .

Keywords: Biochemical recurrence; PSMA PET/CT; Prostate cancer; Prostate-specific membrane antigen.

Fig. 1

Kaplan–Meier plots comparing the clinical progression-free survival of patients with a prior negative PSMA PET/CT. Subgroup analyses are presented according to: (A) receipt of salvage radiotherapy or follow-up with no further treatment; and (B) initial ISUP grade (Note: ISUP grade records were unavailable for 3 patients). The curves are truncated when the number at risk falls below 5

Fig. 2

A 70-year-old patient with biochemical recurrence (PSA, 4 ng/mL; ISUP grade 3) after radical prostatectomy. Maximum Intensity Projection (MIP) of baseline [¹⁸F]DCFPyL PET/CT (A) shows tracer accumulation in the ureters but no evidence of clinical recurrence. The patient was followed by clinical/radiologic examinations. No recurrent prostate cancer was localized on repeat [¹⁸F]DCFPyL PET/CT scan after 25 months (PSA, 3.5 ng/mL) (B)

Fig. 3

A 76-year-old patient with biochemical recurrence (PSA, 0.61 ng/mL; ISUP grade 5) after radical prostatectomy. Maximum Intensity Projection (MIP) of baseline [¹⁸F]DCFPyL PET/CT (A) shows no evidence of clinical recurrence. The patient was followed by clinical/radiologic examinations. Repeat [¹⁸F]DCFPyL PET/CT after 28 months (PSA, 8.78) (B) demonstrates multiple PSMA-avid lymph nodes involving the retrocrural, paraaortic, bilateral common iliac, left external iliac and mesenteric lymph nodes, as well as PSMA-avid osseous lesions involving the right acetabulum, T6 and T12 vertebral bodies