ANAHEIM, CA—Gleason scores of tumor grade are important in decision-making for men with prostate cancer, but may not be the best indicator for risk of recurrence, according to data presented here at the most recent Annual Meeting of the American Urological Association.
In a study by researchers at the University of Texas MD Anderson Cancer Center in Houston, disease confined to the prostatectomy specimen was the only independent predictor of recurrence, when compared with patient age, clinical stage, preoperative PSA, and Gleason grade. In addition, researchers at Memorial Sloan-Kettering Cancer Center in New York City, reported that the prognostic value of calculating the percent volume of Gleason Grades 4 and 5 cancer in a prostatectomy biopsy specimen was minimal.
These findings may have an impact on the development of new nomograms to assess risk of treatment failure. The new data could also influence recommendations for the use of adjuvant therapy.
“Men are not likely to need adjuvant therapy as long as the prostate cancer tumor is organ-confined on pathology,” Badar M. Mian, MD, a fellow in the Department of Urology at MD Anderson, said during his presentation. “Even patients with high-grade tumors will experience relapse-free survival similar to that of men with lower-grade disease if the disease is organ confined.”
Dr. Mian reported that men who had undergone radical prostatectomy and had Gleason scores of 8 or higher had recurrence-free survivals similar to that of men with scores of 6 or 7. Patient age, ethnicity, clinical stage, and preoperative PSA had no significant effect on disease recurrence, and Gleason score was not an independent predictor of recurrence.
“Specimen-confined disease was the only independent predictor of prostate-cancer recurrence,” Dr. Mian said.
Patients selected to undergo surgery are more likely to have specimen-confined disease that results in favorable biochemical relapse-free rates, he noted. “We don't believe adjuvant therapy is warranted in these patients.”
The MD Anderson authors acknowledged that prostate cancer patients with a Gleason score of 8 have typically failed to respond early and often, but the researchers said that stage migration within PSA ranges may have accounted for that trend.
“Screening for prostate cancer has resulted in an increase in the detection of organ-confined prostate cancer in the modern era,” they said. “And in properly selected patients, poorly differentiated prostate cancer is a surgically curable disease.”
Dr. Mian and his colleagues identified 190 patients whose prostatectomy specimens were assigned a Gleason score of 8 or higher and who did not receive any neoadjuvant or adjuvant therapy. Median follow-up was 60 months, and disease recurrence was defined as any detectable PSA level above 0.1 ng/ml.
Of the 190 patients, 29 percent had organ-confined disease, 25 percent had extraprostatic extension with negative surgical margins, and 12 percent had positive margins with extraprostatic extension.
The five-year disease-free survival rate for the entire group was 81 percent, and the seven-year rate was 68 percent. Patients with organ-confined or specimen-confined disease had five-year disease-free survival rates of 88 and 83 percent, respectively.
Fourteen patients (7%) with micrometastatic disease to pelvic lymph nodes had a five-year disease-free survival of 57 percent. Of the 190 patients, 79.5 percent had no evidence of prostate cancer after a median follow-up of 60 months.
“On multivariate analysis, specimen-confined disease was the only independent predictor of disease recurrence,” Dr. Mian concluded. “Patient age, ethnicity, clinical stage, and preoperative PSA had no significant effect on disease recurrence.”
Percent Volume—Minimal Value
The percent volume of Gleason Grades 4 and 5 cancer in a prostatectomy biopsy specimen was found to be the most important predictor of postoperative three-year PSA failure in the Sloan-Kettering study, but the researchers believed its impact on prognostication was minimal.
“In our analysis of single parameters, Gleason Grade 4 and 5 could increase the predictive accuracy of relapse at three years by just one percent,” said Markus Graefen, MD, a urology fellow at Sloan-Kettering at the time of the study who is now an attending physician at University Hospital in Hamburg. “Calculating the percent of high-grade cancer volume in a prostatectomy biopsy specimen may not be worth the effort.”
The volumetric assessment required to calculate high-grade cancer volume adds from 20 to 30 minutes to the laboratory time necessary for each patient, he noted.
In a group of 673 men treated exclusively with radical retropubic prostatectomy, the Memorial researchers correlated time to PSA failure with one of four variables: prostatectomy Gleason sum, percent of Gleason pattern 4 or 5 in the specimen, total cancer volume, and the volume of cancer expressing Gleason pattern 4 or 5. The strongest predictor for the 156 patients who had biochemical failure was the percent of Gleason score 4 or 5 on pathology after surgery, Dr. Graefen said.
But during his presentation, Dr. Graefen remarked that prognosis could be made almost as accurately with lymph node status, surgical margin status, involvement of the seminal vesicles, Gleason sum, and organ-confined disease—parameters that are already readily available.
Free PSA Does Not Predict Failure
In a separate presentation at the meeting, Dr. Graefen reported on a study that found that the percent of free PSA had no independent statistically significant association with higher pathologic stage, organ confined status, or post-treatment PSA outcome in patients undergoing radical prostatectomy for localized prostate cancer.
A monoclonal assay tested the value of percent-free PSA in predicting pathologic stage in 777 consecutive men who underwent radical prostatectomy, and also in predicting PSA failure in a subset of 581 men who had long-term follow-up.
“The percent of free PSA reached significance in predicting pathologic stage, but it failed to predict PSA failure,” Dr. Graefen concluded.
He added that for a subset of 416 men with T1c disease, biopsy grade was the only significant variable in predicting PSA failure.