Risk factors for primary radiation failure and timing of progression

Zumsteg et al. searched the database at Memorial Sloan Kettering Cancer Center (MSKCC) to determine the risk factors associated with cancer progression after primary radiation treatment, and the timing of progression. Their retrospective analysis looked at records of 2,694 patients treated at MSKCC with radiation doses between 76 Gy to 86 Gy. The median follow-up was 83 months for all patients and 122 months for those who experienced biochemical failure (defined as nadir+2). They did not report what, if any, salvage treatment was used. The researchers found:

• ·      23% of patients experienced biochemical failure.
• ·      The median time from biochemical failure to detection of distant metastases was 5.4 years.
• ·      The median time from biochemical failure to prostate cancer-specific mortality was 10.5 years, 5.1 years after metastases were detected.
• ·      Risk of clinical progression following biochemical failure were independently associated with:

o   Shorter PSA doubling time

o   Higher clinical stage

o   Higher Gleason score

o   Shorter time to biochemical failure

John Hopkins reported that for men treated with surgery, 19% experienced biochemical failure. Some of the difference may be attributable to the inadequate dose of radiation (76 Gy) used on some patients, or that those patients were diagnosed with more aggressive disease. The median time from biochemical recurrence to detection of distant metastases was 8 years, 3 years among those who did not have salvage radiation after biochemical recurrence (Antonarakis et al.), The shorter time in the radiation study may reflect the fact that patients choosing radiation have historically been older and further progressed at time of diagnosis. The median time to death after metastases were detected was 5 years – identical in both studies. They all report the same risk factors for clinical progression.

The numbers reported for initial radiation therapy are similar, at first blush, to those reported for initial prostatectomy. Because there will probably never be a randomized clinical trial of surgery vs. radiation, it is tempting for the patient faced with the choice of initial therapy after diagnosis to compare these datasets, both from top institutions in their respective specialty. While I would very much like to see the patient characteristics and the data stratified by risk group and salvage treatment, if any, there does seem to be a similar overall pattern. Some patients will have already experienced undetected micrometastases before treatment, and they will not be cured by either therapy using current methods. Other patients, most in fact, will be cured by either therapy.