THE "NEW" PROSTATE CANCER INFOLINK

There have been several attempts to clearly define surrogate endpoints for prostate cancer-specific survival that could be used to shorten the length of clinical trials investigating the merits of specific forms of treatment for prostate cancer. A new analysis of data from the 1,554-patient RTOG 92-02 trial has further explored two such possibilities.

The Radiation Therapy and Oncology Group (RTOG) 92-02 trial was a randomized multi-center study of treatment of men with localized prostate cancer. It examined the use of 4 months of neoadjuvant and concurrent androgen deprivation therapy together with external beam radiation therapy followed by random assignment of patients to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm).

Ray et al. investigated the utility of two possible surrogate endpoints based on data from this trial:

• The presence of clearly defined distant metastases
• “General clinical treatment failure,” which they defined as “documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/ml or higher after radiation therapy)

Data from 1,521/1,554 of the original patients enrolled in the trial were evaluable for this analysis, and study follow-up data on these patients at 3 and at 5 years post-treatment was used to assess the potential of the proposed surrogate endpoint to predict outcomes at 10 years, based on the use of the Prentice criteria.

The results of the analysis by Ray and colleagues show that:

• At 3 years, 1,364 patients were alive and contributed data for analysis.
• At 3 years, both distant metastasis and general clinical treatment failure were consistent with all four of Prentice’s criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years.
• At 5 years, 1,178 patients were alive and contributed data for analysis.
• Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years, both endpoints were consistent with Prentice’s remaining criteria.

The authors conclude that, “Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years.” However, they point out, entirely appropriately that these endpoints need to be validated through their application to other sets of data from other randomized trials.

For readers unfamiliar with the Prentice criteria, these are a set of sophisticated statistical criteria that must be met for a specific “marker” to be considered as having significant potential as a surrogate endpoint. We do not intend to try to examine these criteria in detail on this site. Those who are interested in such matters should click here. However, what these criteria imply, in English, is that:

• Treatment actually has a significant impact on the proposed surrogate endpoint.
• Treatment actually has a significant impact on the real endpoint.
• The surrogate endpoint has a significant impact on the real endpoint.
• The full effect of treatment on the real endpoint is actually captured by the surrogate endpoint.

In the above study, it was the first of these criteria that was not met at 5 years.

Filed under: Drugs in development, Management, Treatment | Tagged: endpoint, surrogate, survival |