Clinical investigation
Prostate
Isotope and Patient Age Predict for PSA Spikes After Permanent Prostate Brachytherapy

https://doi.org/10.1016/j.ijrobp.2007.01.066Get rights and content

Purpose: To evaluate prostate-specific antigen (PSA) spikes after permanent prostate brachytherapy in low-risk patients.

Methods and Materials: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing 103Pd and 125I for low-risk disease. Of the 164 patients, 61 (37.2%) received short-course androgen deprivation therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA measurements were obtained per patient. Biochemical disease-free survival was defined as a PSA level of ≤0.40 ng/mL after nadir. A PSA spike was defined as an increase of ≥0.2 ng/mL, followed by a durable decline to prespike levels. Multiple parameters were evaluated as predictors for a PSA spike.

Results: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone-naive 125I patients and 57 hormone-naive 103Pd patients, 21 (45.7%) and 8 (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time between implantation and the spike was 22.6 months and 18.7 months for 125I and 103Pd, respectively. In patients receiving neoadjuvant androgen deprivation therapy, the incidence of spikes was comparable between isotopes (125I 28.1% and 103Pd 20.7%). The incidence of spikes was substantially different in patients <65 years vs. ≥65 years old (38.5% vs. 16.3%). On multivariate Cox regression analysis, patient age (p < 0.001) and isotope (p = 0.002) were significant predictors for spike.

Conclusion: In low-risk prostate cancer, PSA spikes are most common in patients implanted with 125I and/or <65 years of age. Differences in isotope-related spikes are most pronounced in hormone-naive patients.

Introduction

Biochemical control after local treatment for prostate cancer is defined by a stable, nonrising prostate-specific antigen (PSA) level. Unlike after radical prostatectomy in which the PSA level declines to undetectable levels within a few weeks, the PSA kinetics after brachytherapy can be highly variable. Although PSA normalization usually follows first-order kinetics, transient PSA spikes (bounces) occur in a substantial minority of patients (1, 2). The PSA spike phenomenon, first described in 1997 by Wallner and colleagues (1), most commonly occurs 12–30 months after implantation. It is thought to be a result of compromised membrane integrity in the PSA-producing epithelium and has not proved to be of prognostic consequence in brachytherapy patients (1, 2, 3, 4, 5, 6). However, if not appropriately identified, PSA spikes can be a source of inappropriate diagnostic and therapeutic intervention, including radiographic evaluation, prostate biopsy, androgen deprivation therapy (ADT) and salvage local therapy.

Prostate-specific antigen (PSA) spikes have been reported to occur in 17–84% of permanent prostate brachytherapy patients (3, 7). This wide range in the incidence of PSA spikes is in part due to a multitude of single institutional definitions (2, 3, 4, 7, 8, 9, 10) (Table 1). Furthermore, it is likely that some PSA spikes may be nothing more than physiologic and/or PSA assay variation (11). Prestigiacomo and Stamey (11) reported that the serum PSA level can vary by as much as 35% in patients without prostate cancer. On the basis of these findings, Pruthi (12) recommended that a PSA spike be defined as a rise in PSA level of <35% from baseline. To date, however, only one study has used this definition (3).

Neoadjuvant ADT is often used before brachytherapy for cytoreduction and results in a PSA profile different than that of hormone-naive patients (13). In a retrospective evaluation, the peak PSA level in ADT brachytherapy patients occurred approximately at the same time (15–20 months) as in hormone-naive patients, but the median peak PSA level was substantially less in the ADT-treated patients (0.10 vs. 0.40 ng/mL) (13). ADT has not proved to influence the incidence of PSA spikes (7, 9).

In an attempt to clarify the clinical significance of PSA spikes, we evaluated the incidence, temporal onset, and impact of the clinical, treatment, and dosimetric parameters on the development of a PSA spike in low-risk patients prospectively randomized to 103Pd or 125I with or without short-course ADT (14).

Section snippets

Methods and Materials

Between October 1999 and June 2003, 166 of a total of 600 patients with low-risk disease (Gleason score 5–6, PSA ≤10 ng/mL, and clinical Stage T1c–T2b, 2002 American Joint Committee on Cancer staging system) were randomized to 103Pd (125 Gy, American Brachytherapy Society 2000 guidelines) vs. 125I (145 Gy, American Association of Physicists in Medicine Task Group 43) at the Schiffler Cancer Center (Wheeling, VA). An additional 433 patients were randomized at the Puget Sound Veterans Affairs

Results

Table 2 summarizes the clinical, treatment, and dosimetric parameters, stratified by isotope and ADT status. Of the 164 patients, 86 were randomized to 103Pd and 78 to 125I. Of the 164 patients, 103 (62.8%) were hormone naive and 61 (37.2%) had received short-course ADT. The overall mean and median follow-up was 5.4 ± 1.0 years and 5.4 years, respectively. The hormone-naive patients were, on average, 2.5 years younger than the patients who received ADT (64.5 vs. 67.0 years, p = 0.049) and had a

Discussion

Biochemical control after definitive local treatment for prostate cancer is defined by a stable, nonrising PSA level. After radical prostatectomy, the PSA level becomes undetectable within weeks; however, after brachytherapy PSA kinetics can be highly variable with a complex pattern of normalization. Spikes result in substantial patient and physician anxiety, with the possibility of unnecessary diagnostic and/or therapeutic intervention. Intensive physician and prebrachytherapy patient

Conclusion

In low-risk prostate cancer patients, PSA spikes were most common in patients implanted with 125I and/or <65 years old. Differences in isotope-related spikes were most pronounced in hormone-naive patients.

References (19)

There are more references available in the full text version of this article.

Cited by (30)

  • Prostate-specific antigen spikes with <sup>131</sup>Cs brachytherapy: Is there a difference with other radioisotopes?

    2012, Brachytherapy
    Citation Excerpt :

    It has been shown to vary based on age, use of hormone therapy, and radioisotope used. In the study by Bostancic et al. (6) in the hormone-naive patients, the mean time between implantation and the spike was 22.6 and 18.7 months for 125I and 103Pd, respectively. The mean time of occurrence in our series was 12.5 months, which appears to be earlier than most reported series for 125I and 103Pd.

  • Prostate specific antigen bounce is related to overall survival in prostate brachytherapy

    2012, International Journal of Radiation Oncology Biology Physics
View all citing articles on Scopus

Conflict of interest: none.

View full text