International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationPostoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy
Introduction
When biochemical failure after radical prostatectomy (RP) occurs, selecting patients most likely to achieve durable control with salvage radiotherapy (RT) is often challenging. Although no randomized trials exist for salvage radiotherapy, its role as the only potentially curative treatment for biochemical relapse after prostatectomy has been demonstrated among numerous retrospective studies, and was most recently summarized in a multi-institutional pooled data analysis 1, 2 and a comprehensive review of the literature (3). Together these reports, along with the American Society for Therapeutic Radiation and Oncology (ASTRO) Consensus statement (4), form the basis for optimal patient selection and therapeutic guidelines. The prognostic factors commonly identifying patients likely to succeed salvage radiotherapy nclude Gleason score, pathologic T-stage, margin status, preradiotherapy prostate-specific antigen (PSA) level, and PSA doubling time.
In the last few years, several studies have shown PSA kinetics to be a powerful index of biologic behavior and a predictor of failure of definitive treatment by either surgery or radiotherapy, as well as a predictor of prostate cancer–specific survival 5, 6, 7, 8, 9, 10, 11. Specifically, a pretreatment PSA velocity >2 ng/ml/yr or a short post-treatment PSA doubling time (either <3 months or <10 months) were predictive of these worse outcomes. PSA kinetics (i.e., the change in PSA level over time) can be analyzed in two separate ways: as PSA velocity or as PSA doubling time. There is no reason for one to assume a priori that the rate of PSA change with time follows either zero-order kinetics (i.e., a linear change with time that is best quantified by prostate-specific antigen velocity) or first-order kinetics (i.e., an exponential change with time that is best expressed by prostate-specific antigen doubling time). This is particularly true when considering PSA changes at very low absolute levels and over a short time interval. Initially, PSA kinetics could start off as zero-order kinetics before evolving into first-order kinetics as tumor burden and the number of separate foci expand. We propose that postoperative (postop) PSA kinetics may help to distinguish between locally recurrent versus distant disease. Within the context of the need for improved patient selection for salvage RT as well as for identifying patients who might be better suited for alternative therapeutic regimens, we examined postop PSA kinetics as a factor among many others predicting biochemical relapse-free survival after salvage RT.
Section snippets
Patient population
Between 1984 and 2005, 159 patients received radiotherapy at Stanford University School of Medicine after radical prostatectomy (RP) and had a minimum follow-up of 1 year. A complete review of their preoperative (preop) and postop medical records was performed, including their surgical pathology findings and follow-up PSA values. No patient had received hormone therapy before RP. The 81 patients who met the following criteria formed the study population: undetectable PSA after RP;
Results
There were 37 biochemical relapses observed after salvage RT. Univariate analysis demonstrated the following factors as significant in achieving bRFS: adding TAS, decade of salvage RT, higher prostate bed doses, pelvic nodal RT, pre-RT PSA <1 ng/ml, and postop PSAV (either as a continuous variable or with several dichotomous cut-points: 0.5, 1.0, and 1.5 ng/ml/yr). Table 2 summarizes the univariate results. Kaplan-Meier bRFS curves are shown in Fig. 1 for three postop PSAV cut-points: 0.5, 1,
Discussion
Salvage radiotherapy still remains the only potentially curative treatment for biochemical failure after radical prostatectomy. In our study the 5-year actuarial rate of disease-free survival for all patients was 50%, and ranged from ∼60% for favorable to ∼30% for unfavorable subsets. Optimizing patient selection with the use of pretreatment PSA, pathologic T-stage, pathologic Gleason score, and PSA kinetics will improve the identification of patients best suited for salvage RT alone and those
Conclusion
In conclusion, for patients receiving salvage RT for biochemical failure after prostatectomy the inclusion of PSA kinetics and, specifically postop PSAV, provides a powerful biologic indicator of those patients likely to fail salvage RT, and helps to identify those who would likely benefit from a salvage regimen addressing systemic disease. For well-selected patients, salvage RT is a very effective local treatment with a significant potential for cure.
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Cited by (16)
PSA nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure
2012, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :In follow-up, PSA values are routinely checked. Most worrisome after definitive treatment is a rising PSA, and there has been recent literature to address whether the absolute PSA increase or the PSA velocity predict for treatment failure and/or survival outcomes (1–4). In general, these analyses overlook an earlier clue that may also predict for clinical outcomes.
The possibility of hormone-mediated PSA derangement in prostate cancer treatment
2018, International Journal of Radiation ResearchSignificance of early prostate-specific antigen values after salvage radiotherapy in recurrent prostate cancer patients treated with surgery
2015, International Journal of Urology
Conflict of interest: none.