It is well known that a Gleason score of 8-10 at the time of diagnosis is predictive of less good long-term outcomes in the treatment of prostate cancer. However, it is also well known that many men who present with early stage prostate cancer and a Gleason score of 8-10 do very well following radical surgery.
A Spanish group (Rioja Zuazu et al.) have now presented data from their series of > 750 radical prostatectomy patients treated between 1990 and 2004. Of these patients, 108 had Gleason scores of 8-10 at time of biopsy.
The median PSA of these 750+ patients at time of diagnosis was 12 ng/ml and 50 percent of them were clinical stage T2. What Rioja Zuazu et al. have done is to compare the outcomes of the group of 108 patients with Gleason 8-10 with the rest and, within the Gleason 8-10 group, analyze which variables were associated with progression and progression-free survival.
Their results can be summarized as follows:
- Mortality data
- 62.7 percent (490/781) of their patients are still alive and free of biochemical progression
- 24.8 percent (194/781) are alive with biochemical progression
- 2.9 percent (23/781) have died of prostate cancer specifically
- 1.9 percent (15/781) have died of other causes
- 7.6 percent (59/781) have been lost to follow-up
- Biochemical progression data for the whole series (781 patients)
- A clinical Gleason score 8-10 alone is a statistically significant influence factor biochemical progression
- Progression-free survival of patients with Gleason 8-10 disease was 56 ± 5 percent at 3 years and 35 ± 7 percent at 5 years (significantly worse than the rest of the group; p < 0.0001)
- Even in multivariate analysis, a biopsy Gleason score of 8-10 was an independent prognostic factor for biochemical disease progression (as were the clinical stage, the PSA level, and the size of tumor on the biopsy).
- Biochemical progression data for the Gleason score 8-10 group alone
- Influence factors on progression-free survival were PSA level and pathological (post-surgical) stage
- Patients with pT2 disease had a significantly better progression-free survival than those with pT3 disease at 3 years (80 ± 6 vs. 54 ± 13 percent) and at 5 years (40 ± 7 and 27 ± 7 percent).
- Gleason 8-10 patients with a PSA < 11 ng/ml have better 3-year (74 ± 7 vs. 30 ± 22 percent ) and 5-year (40 ± 7 vs. 26 ± 7 percent) progression-free survival than those with a PSA level >11 ng/ml
The authors conclude that a biopsy Gleason score of 8-10 is a negative independent prognostic factor on progression-free survival (which is nothing new). However, they also conclude that prognosis for these patients is better if they present with a pre-surgical PSA level < 11 ng/ml and are found to have a pathological stage of pT2 post surgery.
What is also of considerable interest to The “New” Prostate Cancer InfoLink, however, are the outcomes of surgical treatment alone for men with early stage prostate cancer and a Gleason score of 8-10.
Rioja Zuazu et al. have shown that in this group of men, even when the pre-surgical PSA level is < 11 ng/ml and the pathologic stage is pT2, the 5-year survival based on surgery alone is only 40 ± 7 percent. We therefore have three questions:
- What is the appropriate adjuvant therapy for men with Gleason 8-10 prostate cancer, pathological stage pT2, and PSA < 11 ng/ml who have been surgically treated, or should they receive expectant management?
- Can we differentiate between the 60 percent of men in this group who will have biochemical progression within 5 years and those who won’t, and should they be treated differently?
- What is the appropriate adjuvant treatment for men with Gleason score 8-10 and a PSA > 11 ng/ml and those with a Gleason score of 8-10 and a pathological stage of pT3 post surgery?
It is clear that better guidelines need to be put in place for these men. Adjuvant radiation or adjuvant hormone therapy (or both) may not be the best strategy. Should most of these men be placed on clinical trials?