Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy

Abstract

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. Design, setting, and participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. Outcome measurements and statistical analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. Results and limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA !0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%. Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ! 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. Patient summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of !0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

Analysis of factors associated with positive surgical margins and the five-year survival rate after prostate cancer resection and predictive modeling

“…However, the proportion of patients with locally progressive intermediate-risk and high-risk prostate cancer undergoing prostatectomy has recently increased considerably (17), which in turn has significantly increased the risk of postoperative PSM. Several studies have shown that postoperative PSM in prostate cancer is correlated with post-penetration Gleason score, PSA level, tumor infiltration in seminal vesicles, clinical stage of the tumor, size (volume) of the prostate, proficiency of the surgeon, the age and body mass index of the patient, and biopsy nerve infiltration (18)(19)(20)(21).…”

Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer

“…Follow‐up consisted of PSA testing 1 month after surgery, and, subsequently, further measurements were performed at time intervals of 3–6 months. PSA responders were defined by PSA decrease after sLND ≤0.3 ng/ml 18 . The administration of additional treatments after sLND was left at the discretion of each surgeon.…”

“…PSA responders were defined by PSA decrease after sLND ≤0.3 ng/ml. 18 The administration of additional treatments after sLND was left at the discretion of each surgeon. Clinical recurrence (CR) after sLND was defined as positive conventional imaging in presence of a rising PSA, with patients censored on the date of last evidence of freedom from CR.…”

Salvage lymphadenectomy after primary therapy with curative intent for prostate cancer

“…With a cutoff of 0.3 ng/ml for the first postoperative PSA and a median follow-up of 48 months, men with persistently elevated PSA had a higher risk of cancer-specific mortality (hazard ratio 2.59) after sLND [32 ▪▪ ]. The authors demonstrated that early ADT use after sLND was beneficial for patients with PSA persistence after surgery (hazard ratio 0.49) [32 ▪▪ ].…”

“…Gleason grade group 5 (hazard ratio 2.04), longer time from RP to PSA rise (hazard ratio 0.99), ADT for PSA rise after RP (hazard ratio 1.47), retroperitoneal uptake on PET/CT scan (hazard ratio 1.24), three or more positive spots on PET/CT imaging (hazard ratio 1.26), and higher PSA levels at sLND (hazard ratio 1.05; P < 0.0001) were found to be significant predictors of early clinical recurrence after sLND [21]. Recently, the same group found an inverse relationship between the first PSA after sLND and the probability of CSS [32 ▪▪ ]. With a cutoff of 0.3 ng/ml for the first postoperative PSA and a median follow-up of 48 months, men with persistently elevated PSA had a higher risk of cancer-specific mortality (hazard ratio 2.59) after sLND [32 ▪▪ ].…”