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

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: June 4, 2006

Presenter: A.J. Stephenson
Presenter's Affiliation: Cleveland Clinic, Cleveland, OH
Type of Session: Keynote

Background

Following radical prostatectomy, 25% of patients experience a rising PSA.
Risk factors for metastatic disease include a rapid PSA doubling time, high grade Gleason, and a short disease-free interval.
High risk patients are often recommended to undergo androgen deprivation therapy (ADT) even though it produces a number of significant side effects and is not a curative treatment.
Five studies of this topic suggest that >50% of patients with rising PSA may have an isolated local recurrence.
Salvage radiotherapy for rising PSA post prostatectomy offers a potentially curative modality.
The authors' objective was to develop a nomogram to predict the outcome after salvage radiotherapy that considers all of the characteristics of a patients' cancer rather than a single parameter.

Materials and Methods

1540 patients who received salvage radiotherapy following prostatectomy between 1987 and 2005 were identified.
Radiation was delivered at 1 of 17 North American tertiary referral centers.
No patient received adjuvant androgen deprivation therapy.
The median follow-up was 53 months.
The primary endpoint was disease progression which was defined as PSA >=0.2ng/ml followed by another increase, initiation of systemic therapy, or clinical recurrence.
The secondary endpoint was complete PSA response (nadir <= 0.1ng/ml).
A multivariate Cox regression analysis was performed in order to find significant predictors of disease progression.

Results

Disease progression after salvage therapy was seen in 866 patients (56%).
The 5 and 10 year progression free probabilities were, respectively: 32% (95%CI 28%-35%) and 19% (95%CI 15%-23%).
Significant variables in the nomogram included: pre-radiotheapy PSA, Gleason score, neoadjuvant androgen deprivation, negative surgical margins, PSA at biochemical relapse, PSA doubling time, and regional lymph node metastasis.
A nomogram was constructed using these factors which was accurate and discriminating with a concordance index of 0.68
When examining patients whose pre-radiotherapy PSA was <= 0.5ng/ml, the 6 year PFS was 48% with a median PFS of 69 months.

Author's Conclusions

This is the first model to predict the outcome of any salvage therapy for a rising PSA.
Early intervention is associated with an improved outcome; up to 50% of patients are potentially curable if treated when their PSAs are <= 0.5.
This nomogram is superior to published predictors of metastasis progression.

Clinical/Scientific Implications

The authors presented a retrospective review of a large number of patients treated with salvage radiotherapy for rising PSA post prostatectomy. They have published a nomogram with a decent concordance index. They quantified what many physicians have known about the factors which predict for a poor outcome when a patient has a rising PSA. Men with rising PSA post prostatectomy need to be counseled carefully before salvage radiotherapy is prescribed. The combination of salvage radiotherapy and prostatectomy places men at a high risk for significant negative side effects including impotence and incontinence. It would be nice if this analysis could help us decide the radiation doses and field sizes that are the most effective in this setting. Finally, the use of concomitant androgen deprivation and radiotherapy for definitive treatment of high risk prostate cancer patients has been well established. It seems logical that a similar strategy may improve outcomes in the salvage setting as well. However, we will need further data to prove this hypothesis.