Elsevier

Practical Radiation Oncology

Volume 4, Issue 6, November–December 2014, Pages 409-414
Practical Radiation Oncology

Original Report
Prostate-specific antigen decline during salvage radiation therapy following prostatectomy is associated with reduced biochemical failure

https://doi.org/10.1016/j.prro.2014.01.002Get rights and content

Abstract

Purpose

To evaluate the prognostic value of prostate-specific antigen (PSA) decline during salvage radiation therapy (SRT) after prostatectomy.

Methods and materials

We reviewed an institutional database and identified all prostate cancer patients who were treated with SRT between the years 2003 and 2010, had at least 1 PSA measurement during their SRT course, and had no history of androgen deprivation therapy use prior to or during SRT. Disease characteristics, treatment information, and clinical outcomes data were tabulated for each patient. The PSA response during SRT was defined as a PSA decline of at least 0.2 ng/mL compared with the pretreatment PSA level. Bivariate and multivariate analyses using Cox proportional hazards modeling were performed to identify predictors of biochemical recurrence.

Results

Sixty-four patients met eligibility criteria for this analysis. Median PSA before SRT was 0.63 ng/mL (interquartile range: 0.42-1.00). With a median follow-up time of 70 months after SRT, 5-year actuarial rates for biochemical control and metastasis-free survival were 61% (95% confidence interval [CI], 48%-75%) and 88% (95% CI, 79%-97%), respectively. The median number of PSA measurements per patient during SRT was 3 (range, 1-5). On bivariate analysis, PSA response during SRT and positive surgical margins were significantly associated with a decreased risk of biochemical recurrence (BR), with hazard ratios of 0.160 (95% CI, 0.059-0.431, P < .001) and 0.396 (95% CI, 0.168-0.935, P = .035). On multivariate analysis, PSA response during SRT and positive surgical margin were independent, favorable predictors for BR, with hazard ratios of 0.171 (95% CI, 0.063-0.463, P < .001) and 0.411 (95% CI, 0.177-0.956, P = .039). The 5-year biochemical control rate for PSA responders was 81%, compared with 37% for nonresponders (P < .001).

Conclusions

Prostate-specific antigen decline during SRT may be a valuable prognostic factor for subsequent clinical outcomes. Future studies should investigate the value of monitoring PSA during SRT and how PSA response may be used to personalize therapy.

Introduction

Approximately 30% of patients who undergo prostatectomy as primary treatment for localized prostate cancer develop biochemical disease recurrence within 10 years.1., 2. These patients are at increased risk for the development of distant metastases and for prostate cancer-specific mortality. Treatment options for biochemical recurrence (BR) after prostatectomy include salvage radiation therapy (SRT), androgen deprivation therapy (ADT), or a combination of both.3 Established prognostic factors for patients treated with SRT include pre-SRT PSA level, prostatectomy Gleason score, postprostatectomy PSA doubling time, and surgical margin status.4., 5.

The PSA response during SRT has been evaluated as a potential prognostic factor in a few series, with mixed results.6., 7. Here we review our institution’s experience with SRT to determine if PSA response predicts for biochemical and clinical disease recurrence. We hypothesized that PSA decline during SRT could be an early prognostic factor and identify patients likely to have favorable outcomes following SRT.

Section snippets

Patient selection

In this institutional review board-approved study, we utilized a departmental database to identify all patients who were treated with SRT for biochemical recurrence of prostate cancer after prostatectomy in the years 2003-2010. Patients who met the following criteria were included in this study: were at least 6 months postradical prostatectomy at time of BR, had 2 consecutive measurements of at least 0.2 ng/mL or a single measurement of PSA of at least 0.4 ng/mL after prostatectomy, had a

Study subjects

A total of 64 patients met all inclusion criteria and were included in this analysis. Patient characteristics are summarized in Table 1; 48.4% of patients had Gleason score 7, 28.1% had Gleason score of 6, and 59% had a positive margin. Median time from radical prostatectomy (RP) to initiation of SRT was 35.8 months (interquartile range [IQR], 15.1-65.0). Median PSA before SRT was 0.63 ng/mL (IQR, 0.42-1.00). Eighty-nine percent of the patients received a dose of 66.6 Gy in 1.8 Gy/fraction.

PSA response

The

Discussion

In this single-institution report, we found that surgical margin status was an independent predictor of BR. Additionally, we identified PSA response during SRT as a strong favorable prognostic factor with respect to both BR and distant metastasis.

Our rationale for studying short-term PSA response as a predictor of clinical outcomes following SRT for prostate cancer is that, in most cases, SRT is administered to the prostate fossa without pathologic confirmation of local disease recurrence.

References (21)

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    They have demonstrated a higher detection rate of tumour manifestations than previous tracers and could thus improve the selection of patients for curatively intended treatment with SRT extended to include regional lymph nodes and boost to local recurrence [6–10]. Previous retrospective studies have shown an association between decreasing PSA during SRT and long-term clinical control [11,12]. Based on weekly PSA measurements during prostate bed SRT, we recently confirmed these findings in a prospective clinical trial [13].

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    This information can be used for selecting patients for SRT. Previous retrospective studies have shown an association between PSA change during SRT and long term outcome [19,20]. The identification of robust parameters based on each patient’s instant response to treatment, rather than using pre-treatment factors only, can be used to more effectively identify a group of patients with high risk of recurrence that are more likely to benefit from treatment escalation.

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Conflicts of interest: None.

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