Comparison of outcomes of different biopsy schedules among men on AS

Comparison of outcomes of different biopsy schedules among men on active surveillance for prostate cancer: An analysis of the G.A.P.3 global consortium database (2022, Full Text)

"Abstract
Background
The optimal interval for repeat biopsy during active surveillance (AS) for prostate cancer is yet to be defined. This study examined whether risk of upgrading (to grade group ≥ 2) or risk of converting to treatment varied according to intensity of repeat biopsy using data from the GAP3 consortium's global AS database.

Materials and Methods
Intensity of surveillance biopsy schedules was categorized according to centers’ protocols: (a) Prostate Cancer Research International Active Surveillance project (PRIAS) protocols with biopsies at years 1, 4, and 7 (10 centers; 7532 men); (b) biennial biopsies, that is, every other year (8 centers; 4365 men); and (c) annual biopsy schedules (4 centers; 1602 men). Multivariable Cox regression was used to compare outcomes according to biopsy intensity.

Results
Out of the 13,508 eligible participants, 56% were managed according to PRIAS protocols (biopsies at years 1, 4, and 7), 32% via biennial biopsy, and 12% via annual biopsy. After adjusting for baseline characteristics, risk of converting to treatment was greater for those on annual compared with PRIAS biopsy schedules (hazard ratio [HR] = 1.66; 95% confidence interval [CI] = 1.51–1.83; p < 0.001), while risk of upgrading did not differ (HR = 0.96; 95% CI = 0.84–1.10).

Conclusion
Results suggest more frequent biopsy schedules may deter some men from continuing AS despite no evidence of grade progression."

From the Full Text:

"In conclusion, this study found that more intense biopsy schedules correlated with more frequent conversion to active treatment but not risk of upgrading. While the decision to switch to active treatment is based on a mix of biological and personal factors, the requirement for frequent biopsies may also be influential. In slow-growing tumors like low-risk PCa, it remains to be seen which surveillance protocol is optimal in the long term, and whether individualized protocols can be offered."

Djin

centralPAdude said...
Because of the random nature of the biopsies, the probability of two biopsies being identical in their result is zero. One will be worse than the other. So even if absolutely nothing changed in your prostate over the course of a year, there is a 50% chance the second one will be worse, which you will likely take to mean progression. I wonder how much that statistical fact influences decisions.

It would take quite a while to explain why I don't think this is true. In brief, let's take the more common case of a G6 (3+3) man on AS.

(1) If any repeat biopsy reveals at least one G7 core, you can call this progression, even if there was missed G7 (or higher) at the time of your first biopsy (so the disease didn't progress, only you biopsy result did). At least the G7 has been revealed: this is the crucial information. The chances of higher-grade lesions remaining undetected as repeat biopsies are done drops dramatically (do the math).

(2) A repeat biopsy may even come back negative for cancer--this happens. It doesn't mean your cancer has vanished, just that no core hit cancer. You simply continue on AS.

(3) A repeat biopsy comes back with an increased tumor burden of G6 cancer (more lesions, bilateral lesions, larger lesions, etc.). Some of these men will be advised to leave AS and seek treatment. Again, it may be actual progression/spread of the G6 burden, or simply revealing more accurately what was already there. It doesn't matter.

You can take it to the bank that the members of the G.A.P.3 ("the world's largest centralized database of clinical data from men who have opted to undergo active surveillance for their low-risk prostate") are well-versed in the statistics of repeat biopsies and the heterogeneous nature of prostate cancer (lesions with different Gleason score being present at the same time).

Repeat biopsies don't have to be "identical" for men to remain on AS. If what you say about 50% of biopsies being "worse" or progressing, then few men would be on AS for very long, which is not the case. They are looking for higher-grade lesions and/or a significant increase in the estimated prostate-wide amount of G6. Many men have stable G6 disease for the remainder of their lives and can avoid treatment.

The fact that there are basically two possible outcomes of a biopsy (stable disease or progression) says nothing about their respective likelihoods. You could be hit by lightning tomorrow or not, but the odds aren't fifty-fifty. I'd be buying lottery tickets let and right if my winning or losing on each ticket were even odds.

Djin

centralPAdude said...

...
Well, the point of the paper you cited is that the more frequent you sample, the more likely they are to come off of AS, even though progression among the pools of different sampling rates is the same
....

Yes, the conclusion is that perhaps we can relax or customize the biopsy frequency in some protocols, since men are leaving AS for reasons other than disease progression.

"While reasons for withdrawing from AS without progression are multi-faceted, qualitative evidence indicates that requirement for repeat biopsies, and associated levels of anxiety and uncertainty, can deter some men from continuing on AS."

The authors do go on to say caution is needed about relaxing frequency criteria (e.g. increased G6 burden can occur without progression ). Perhaps better patient education would help. A man coming away from a repeat biopsy thinking "Well, I didn't learn anything new--nothing has changed--it was another unnecessary biopsy and I'm fed up." has the wrong message, which is "Your G6 cancer is still stable as far as we can tell, and it's safe to continue on AS; we'll keep an eye on it so you can get treatment before you ever have serious cancer than can metastasize."