THE "NEW" PROSTATE CANCER INFOLINK

Dall’Era et al. have just reported their contemporary experience with active surveillance (AS) for prostate cancer in 321 men treated at the University of California San Francisco over the past 17 years.

Active surveillance was initally offered to men meeting the following criteria:

• Clinical stage T1/T2a
• PSA < 10 ng/mL
• Less than 33 percent of biopsy cores involved
• Gleason score ≤ 6 (with no Gleason grade 4 or 5 cancer)

Surveillance consisted of serial PSA measurements and DREs at 3- to 6-month intervals, TRUS at 6- to 12-month intervals, and (from 2003 onward) repeat prostate biopsies at 12- to 24-month intervals.

Active treatment was the primary outcome assessed. Evidence of disease progression, defined as an increase in rebiopsy Gleason sum or significant PSA velocity changes (>0.75 ng/mL/yr), was a secondary outcome.

Since 1991, 321 men went on AS and met criteria for this analysis. Results observed in this group of patients were as follows:

• The mean PSA level at diagnosis was 6.5ng/mL.
• The median Gleason score was 6
• The mean percent of positive cores was 20.3 percent.
• The mean patient age was 63.4 years.
• 228/321 patients (71 percent) were stratified as low risk; 83/321 (26 percent) as intermediate risk; and 10/321 (3 percent) as high risk.
• Median patient follow-up was 3.6 years.
• At least two prostate biopsies to evaluate for grade progression were performed in 51 percent of patients
• At least three PSA levels were available in 95 percent of patients, allowing calculation of PSA velocities.
• No patients died of prostate cancer.
• 120 men (37 percent) met at least one criterion for disease progression.
• Definitive therapy was performed in a total of 78/321 men (24 percent) at a median time of 3 years; 26 underwent radical prostatectomy, 35 had radiotherapy alone, 7 had radiotherapy with androgen deprivation therapy, and 9 received primary androgen deprivation therapy.
• Clinical evidence of progression occurred in 52 treated patients, and 26 men were treated because of personal choice.
• A PSAV > 0.75 ng/mL/yr occurred in 78 men (24 percent) and a PSAV > 2ng/ml/yr in 48 men (15 percent).
• Mean PSA doubling time was 6.7 years
• 38 percent of the cohort had an increase in Gleason score on repeat biopsy.
• The overall actuarial probabilities of not receiving treatment at 2 and 5 years were 85 and 67 percent, respectively.
• Men who had an increase in Gleason score on biopsy were 3.9 times as likely to convert to active treatment as men who had no increase.

It should be noted that the inclusion of 10 high-risk patients may imply inclusion of some patients who did not meet strict entry criteria but who elected AS.

The two most striking facts from this study are that 201/321 patients (63 percent) did not meet any criteria for disease progression and that only 78/321 men elected secondary therapy (of whom 26 met none of the criteria for disease progression). In other words, about 269/321 patients (84 percent) were or felt they were effectively managed with AS (even though 26 of them decided to elect active therapy at some point in time).

Dall’Era et al. conclude the following: “Selected individuals with early-stage prostate cancer may be candidates for active surveillance. Specific criteria can be and need to be developed to select the most appropriate individuals for this form of management and to monitor disease progression. A small attrition rate can be expected because of men who are unable or unwilling to tolerate surveillance.”

The “New” Prostate Cancer InfoLink notes that the selection criteria used by Dall’Era et al. in this study are extremely close to those that might be considered appropriate for a diagnosis of “clinically insignificant adenocarcinoma of the prostate” in another blog item earlier this week.