Clinical outcomes of salvage treatment in lymph node-positive prostate cancer patients after radical prostatectomy

Abstract

Introduction: The optimal salvage treatment strategies for lymph node-positive (LNP) patients after radical surgery have not been clearly defined in prostate cancer with biochemical recurrence or persistence of elevated prostate-specific antigen (PSA). In this study, we compared the clinical outcomes of two different salvage treatments, androgen deprivation therapy (ADT) alone versus ADT with radiotherapy (RT). We also investigated prognostic factors that could support the use of ADT with RT in LNP prostate cancer.

Materials and methods: We retrospectively reviewed 94 LNP prostate cancer patients who underwent radical prostatectomy (RP) followed by salvage treatment between 2004 and 2018. Salvage treatments involved either ADT alone or ADT with RT according to the clinical judgment of the physician. We analyzed clinicopathological and treatment factors related to 2nd biochemical failure (2nd BCF), clinical progression (CP), and progression-free survival (PFS). The cumulative failure after salvage treatment was defined as including both 2nd BCF and CP.

Results: The median duration of follow-up was 55 months (interquartile range, 35-97 months). Thirty-seven (39.4%) patients were treated with ADT alone, and 57 patients (60.6%) were treated with a combination of ADT with RT. During follow-up period, the incidence of failure after salvage treatment in the ADT alone group and the combined treatment group was 89.2% and 45.6%, respectively (HR, 22.4; 95% CI 5.43-92.1; P < 0.001). The combination of ADT with RT was associated with better 2nd BCF and PFS than ADT alone (P = 0.007 and P = 0.015, respectively). In multivariate analyses, number of positive LN ≥ 2 and PSA nadir ≥ 0.005 ng/ml after RP were associated with poor 2nd BCF, CP, and PFS after salvage treatment. Salvage by combined ADT plus RT showed better 2nd BCF and PFS than ADT alone. Specifically, patients with number of positive LN ≥ 2 or PSA nadir ≥ 0.005 ng/ml after RP showed better 2nd BCF (P = 0.004) or PFS (P = 0.011) when treated with ADT plus RT rather than ADT alone.

Conclusions: In patients with LNP prostate cancer, salvage ADT plus RT improved 2nd BCF and PFS compared to ADT alone. In particular, when the patients had more than two positive lymph nodes or PSA nadir ≥ 0.005 ng/ml after RP, ADT with RT seems to be a more beneficial salvage treatment resulting in better 2nd BCF and PFS.

Fig 1. Flowchart of included and excluded patients and group assignments.

Abbreviations: ADT, androgen deprivation therapy; LN, lymph node; PLND, pelvic lymph node dissection; PSA, prostate-specific antigen; RP, radical prostatectomy; RT, radiotherapy.

Fig 2. Actuarial treatment outcome curves of patients who received salvage ADT alone vs. ADT with RT.

(A) Actuarial curves for 2^nd biochemical failure in the two groups according to salvage treatment method. (B) Actuarial curves for clinical progression in the two groups according to salvage treatment method. (C) Actuarial curves for progression-free survival according to salvage treatment method. Abbreviations: ADT, androgen deprivation therapy; RT, radiotherapy.

Fig 3. Actuarial curves for the subgroup patients with positive LN ≥ 2 or PSA nadir after RP ≥ 0.005 ng/ml.

(A) Actuarial curves for 2^nd biochemical failure according to salvage treatment method. (B) Actuarial curves for progression-free survival according to salvage treatment method. Abbreviations: ADT, androgen deprivation therapy; LN, lymph node; PSA, prostate-specific antigen; RP, radical prostatectomy; RT, radiotherapy.