The impact of a delay in initiating radiation therapy on prostate-specific antigen outcome for patients with clinically localized prostate cancer

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 5, 2004

Presenter: P.L. Nguyen
Presenter's Affiliation: Harvard Medical School/ University of Pennsylvania
Type of Session: Scientific

Background

It has been demonstrated that prolonged delay between cancer diagnosis and the start of radiation therapy (RT) is associated with decreased local control in head and neck cancer. This study sought to evaluate if a delay in administration of RT had an adverse outcome on PSA outcome following treatment of patients with localized prostate cancer. This question has not been extensively studied in the past. However, an abstract recently reported at the American Urology Association (AUA) conference earlier this year stated that a delay of greater than 3 months between diagnosis and prostatectomy led to worse outcome in patients with high-risk localized prostate cancer.

Materials and Methods

460 patients with clinical T1c and T2 prostate cancer treated with 3D conformal radiation therapy between 1994-2001 were studied
Patients were treated with 70.4 Gy after 95% normalization
Median follow-up was 4.3 years (range 1.5-9.8 years)
Patients were stratified into 2 risk groups: low-risk (< 34% positive biopsies) and high-risk (all others)
Primary endpoint was time to PSA failure (using ASTRO consensus definition), with time measured from date of diagnosis
Cox proportional hazards model was used to evaluate both the continuous predictors of PSA outcome (pre-tx PSA< % positive biopsies, delay in tx) and the categorical predictors (GS = Gleason score, T stage)

Results

Median time delay was 2.5 months.
For the overall group (n=460), the time delay between diagnosis and RT was not statistically significant for PSA survival. Pre-tx PSA, % positive biopsies, stage T2b and T2c disease, and GS 7 (4+3) and GS 8-10 were all significant.
Within the low-risk subgroup (n=219), only PSA and GS 7 (4+3) were associated with PSA outcome.
Within the high-risk subgroup (n=241), pre-tx PSA, % positive biopsies, stage T2b and T2c disease, and GS 7 (4+3) and GS 8-10 were all again associated with PSA outcome.
Importantly, delay in treatment was siginificantly associated with PSA survival in the high-risk group, with a hazard ratio of 1.09 (p=0.013).
The 5-year PSA survival in the high-risk group was 60% for median delay < 2.5 mos vs. 48% for median delay > 2.5 mos (p=0.02).
There was no statistically significant difference in distribution of pre-treatment predictors between the low- and high-risk groups.

Author's Conclusions

Time delay between diagnosis and RT for localized prostate cancer is significantly associated with PSA survival in high-risk patients.
Time delay did not appear to be significant in the low-risk subgroup or the overall group.
One possible reason for seeing this effect in only the high-risk group may be: fewer PSA failure events occurred in the low-risk group compared to the high-risk group (36 vs. 106).
These findings appear to be similar to those recently reported for prostatectomy at the AUA conference.

Clinical/Scientific Implications

This study demonstrates that high-risk patients with localized prostate cancer have worse PSA survival if there is a delay between diagnosis and RT of > 2.5 months. This may be explained in part by the greater risk of disease dissemination during the delay period in patients with higher risk disease. Similarly, these high-risk patients are also more likely to have local disease progression during this time delay. Both of these aspects could lead to PSA failure by ASTRO criteria, and thus to lowered PSA survival.

Future studies might look closer at low-risk patients to determine what the maximal length of "safe" delay really is, as there may be a point beyond 2.5 months at which disease burden is no longer controllable with local RT alone. This study had very few patients whose delay extended beyond 6 months. Longer follow-up of this subgroup is needed to help answer these questions.

Regarding the high-risk group, this study raises the question of whether increasing the RT dose or adding hormonal agents to RT might overcome and counteract the increased failure risk caused by the time delay.

Finally, this study emphasizes the importance of timely, judicious management of prostate cancer patients and the importance of addressing any socioeconomic causes of treatment delay that might be potentially avoidable.

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