Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy

Abstract

Purpose: An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence.

Patients and methods: Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients.

Results: The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69.

Conclusion: Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: Kevin M. Slawin, Oncovance Technologies Consultant: Peter T. Scardino, Oncovance Technologies; Michael W. Kattan, Oncovance Technologies Stock: N/A Honoraria: N/A Research Funds: N/A Testimony: N/A Other: N/A

Figures

Fig 1

(A) Kaplan-Meier estimate of the overall progression-free probability after salvage radiotherapy. (B) Progression-free probability after salvage radiotherapy stratified by preradiotherapy prostate-specific antigen 0.50 or less (blue), 0.51 to 1.00 (yellow), 1.01 to 1.50 (gray), and more than 1.50 ng/mL (red).

Fig 2

Four-year progression-free probability after salvage radiotherapy for 1,326 patients who did not receive androgen-deprivation therapy before or during radiation therapy, stratified by preradiotherapy prostate-specific antigen (PSA), Gleason score, surgical margins, and PSA doubling time (PSADT). RT, radiotherapy; PFP, progression-free probability; CI, 95% CI.

Fig 3

(A) Pretreatment nomogram predicting 6-year progression-free probability after salvage radiotherapy for prostate-specific antigen (PSA) recurrence after radical prostatectomy. (B) Calibration of the nomogram. Dashed line indicates reference line where an ideal nomogram would lie. Solid line indicates the performance of the current nomogram. Dots are quartiles of our data set. Instructions: Locate the patient’s Gleason score on the respective axis. Draw a straight line up to the Points axis to determine how many points toward disease recurrence that the patient receives for his or her Gleason score. Repeat this process for the other 10 disease and treatment parameters. Sum the points and locate this number on the Total Points axis. Draw a straight line down to find the patient’s probability of remaining free of disease progression at 6 years after salvage radiotherapy, provided the patient does not die of another cause first.