Elsevier

European Urology

Volume 76, Issue 1, July 2019, Pages 106-114
European Urology

Prostate Cancer
Persistent Prostate-Specific Antigen After Radical Prostatectomy and Its Impact on Oncologic Outcomes

https://doi.org/10.1016/j.eururo.2019.01.048Get rights and content

Abstract

Background

Persistent prostate-specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP).

Objective

To investigate the impact of persistent PSA at 6 wk after RP on long-term oncologic outcomes and to assess patient characteristics associated with persistent PSA.

Design, setting, and participants

Within a high-volume center database we identified patients who harbored persistent (≥0.1 ng/ml) versus undetectable PSA (<0.1 ng/ml) at 6 wk after RP. Patients with neo- and/or adjuvant androgen-deprivation therapy (ADT) were excluded.

Outcome measurements and statistical analysis

Logistic regression models tested for prediction of persistent PSA. Kaplan–Meier analyses and Cox regression models tested the effect of persistent PSA on metastasis-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS) rates. Propensity score matching (PSM) was performed to test the impact of salvage radiotherapy (SRT) on OS and CSS in patients with persistent PSA.

Results and limitations

Of 11 604 identified patients, 8.8% (n = 1025) harbored persistent PSA. At 15 yr after RP, MFS, OS, and CSS were 53.0% versus 93.2% (p < 0.001), 64.7% versus 81.2% (p < 0.001), and 75.5% versus 96.2% (p < 0.001) for persistent versus undetectable PSA, respectively. In multivariable Cox regression models, persistent PSA represented an independent predictor for metastasis (hazard ratio [HR]: 3.59, p < 0.001), death (HR: 1.86, p < 0.001), and cancer-specific death (HR: 3.15, p < 0.001). SRT was associated with improved OS (HR: 0.37, p = 0.02) and CSS (HR: 0.12, p < 0.01) after 1:1 PSM. Main limitation is missing data on postoperative PSA and duration of salvage ADT.

Conclusions

Persistent PSA is associated with worse oncologic outcome after RP, namely, metastasis, death, and cancer-specific death. In patients with persistent PSA, SRT resulted in improved OS and CSS.

Patient summary

We assessed the impact of persistent prostate-specific antigen (PSA) at 6 wk after radical prostatectomy on oncologic outcomes. Early persistent PSA was associated with worse metastasis-free survival, overall survival, and cancer-specific survival. Salvage radiotherapy may result in a survival benefit in well-selected patients.

Introduction

Radical prostatectomy (RP) can provide good long-term oncological outcomes in patients with localized and locally advanced prostate cancer (PCa) [1], [2], [3]. After RP, prostate-specific antigen (PSA) represents the cornerstone for follow-up of patients. The current European Association of Urology (EAU) PCa guidelines recommend first PSA measurement at 3 mo after RP [4].

However, PSA is expected to be undetectable within 6 wk following RP [5]. Moreover, several investigators focused on persistent PSA after RP and relied on the definition of PSA ≥0.1 ng/ml at 6 wk after RP [6], [7], [8], [9], [10], [11], [12], [13], [14], [15].

Some of them reported an association between persistent PSA after RP and biochemical recurrence (BCR) [11], [13], [15]. Moreover, Ploussard et al. [12] reported that approximately 75% of patients with persistent PSA develop BCR. However, studies investigating the relationship between persistent PSA (≥0.1 ng/ml) at 6 wk and development of metastasis and survival after RP are scant or focus only on subgroups such as pN1 disease or patients with salvage radiotherapy (SRT). Previously, Bianchi et al. [7] reported a higher risk for clinical recurrence and cancer-specific mortality for persistent PSA in RP patients with pN1 disease. In addition, Fossati et al. [6] reported that persistent PSA represents an independent predictor for metastasis. However, the study by Fossati et al. [6] focused only on patients with pN0 who received SRT. Therefore, the impact of persistent PSA on long-term oncologic outcomes and the effect of SRT in patients with persistent PSA following RP need to be clarified.

To address these limitations, we investigated the relationship between persistent PSA at 6 wk after RP and the long-term oncological outcomes, within a large high-volume center database. Specifically, we investigated the relationship between persistent PSA and metastasis-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS). Subgroup analyses focused on patients with persistent PSA. In addition, we tested for risk factors to develop persistent PSA. Finally, the impact of SRT versus no RT on OS and CSS in patients with persistent PSA was studied.

Section snippets

Study population

After Institutional Review Board approval, patients that underwent RP (1992–2016), from a single-institutional high-volume center database (Martini-Klinik Prostate Cancer Center, Germany), were identified.

Patients were stratified according to persistent (PSA ≥0.1 ng/ml at 6 wk after RP) versus undetectable PSA (PSA <0.1 ng/ml).

RP was performed with the use of an open retropubic or robot-assisted approach, as previously described [16]. Moreover, neurovascular bundle preservation was performed with

Descriptive statistics

Of 11 604 identified patients, 8.8% (n = 1025) versus 91.2% (n = 10 579) harbored persistent or undetectable PSA, respectively (Table 1). Around 10% (n = 125) of patients with persistent PSA at 6 wk had an undetectable PSA in the subsequent PSA testing. The median follow-up was 61.8 versus 46.4 mo for patients with undetectable and persistent PSA. Patients with persistent PSA were older (median age: 64.6 vs 64.2 yr, p = 0.006), more frequently had pathologic GG5 (19.6% vs 2.5%, p < 0.001), more frequently

Discussion

PSA after RP represents the cornerstone in follow-up of patients with PCa. Specifically, early PSA values after RP could help to identify patients at risk for worse oncologic outcome. Moreover, early PSA after RP could help to identify patients who benefit from further treatment. However, few previous studies tested the impact of persistent PSA on long-term oncologic outcomes. To address this void, we investigated the relationship between persistent PSA at 6 wk and the long-term oncologic

Conclusion

Persistent PSA at 6 wk after RP represents a strong prognostic predictor for development of metastasis and death after RP. Therefore, early measurement of PSA can be useful in clinical practice to identify patients with high risk for worse oncologic outcome. Moreover, SRT was associated with improved OS and CSS in patients with persistent PSA. In those with persistent PSA and additional risk factors, such as pT3b, GG3–5, positive surgical margin, or pN1, SRT should be considered.

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