RalphV said...
The median followup is irrelevant? You said: “as he continues to add men to his study at an accelerated rate the median will drop” The facts are different. His cohort has remained around 450 men. He has not reported a larger number of men in his cohort.
He has been steadily changing the cohort size. Since January 2000, he stopped adding intermediate and high risk men and has steadily added to the cohort.
Klotz (p.127) said...
Between 1995 and 1999, the study was offered to all favorable-risk patients (ie, Gleason 6 or less, PSA 10 ng/mL or less) and to patients older than age 70 years with PSA up to 15 ng/mL or Gleason up to 3+4. Since January 2000, the study was restricted to favorable-risk patients only. This decision was based on the publication of more convincing evidence of a significant difference in natural history between Gleason 6 and 7 and an interest in studying a more homogeneous population. ... Beginning in 2003, the phase II study was terminated as a formal clinical trial, and active surveillance was offered as a treatment option to patients. The same data were collected prospectively."
Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate CancerAs you can see in the reference below, there were 299 men in the study in 2005 vs 450 now.
Active surveillance with selective delayed intervention: walking the line between overtreatment for indolent disease and undertreatment for aggressive disease.The median follow-up
is irrelevant in determining the PCa-specific survival or cause-specific survival (CSS). What we look at in studies like this is the Kaplan-Meier curve that accounts for those changes in sample size. You can find this on Figure 1b.
Klotz (p.128) said...
CSS is shown in Figure 1B. The 5- and 10-year CSS rates were 99.7% and 97.2%. All prostate cancer–related mortalities (n=5) occurred in men who had been reclassified as higher risk and who were offered radical treatment. These deaths occurred at 3.7, 5.2, 5.3, 8.7, and 9.6 years after diagnosis.
RalphV said...
You also ignored the median age of 70 years. Irrelevant? Not at all when you want to know how will the cancer behave in the long-term. The tracking so far has not been long enough with a substantial number of men.
As you can see, the high proportion of men over 70 was due to his initial accrual criteria, which included men over 70 with intermediate risk (GS3+4 and PSA up to 15). Older men tend to present with higher risk disease, so the effect of their over-representation in the total sample would tend to raise the PC-specific mortality, skewing the results
against AS.
He did look at men under 70 separately, which you can see in Figure 3b. The PCa-specific mortality is negligible. Klotz notes (p.129): "However, even in the men younger than 70 years, the risk of non–prostate cancer mortality was far higher than that of prostate cancer mortality."
Instead, what Klotz found was "Thus, the cohort of 450 men contains only a single patient who was treated after a relatively prolonged period of observation (2 years) and subsequently experienced progression to metastatic disease and death."
As I've said, this is already one of the longest tracking studies for a treatment ever done. It seems clear that AS is a very safe alternative to radical treatment that is excellent at (1) sending for treatment those men who require treatment, while (2) protecting those who don't need immediate treatment from needlessly incurring the harms of treatment. While refinement is always possible, I think you'll agree that based on his study, AS is a safe decision for favorable risk men.
- Allen