Aspirin Use and the Risk of Prostate Cancer Death

[radiation]

any thoughts on this potentially practice-changing study?


Aspirin Use and the Risk of Prostate Cancer Death in Men Treated with Prostatectomy or Radiotherapy:Results from the CaPSURE Database

Purpose/Objective(s)
Substantial experimental evidence suggests that anticoagulants (AC) may inhibit cancer growth and metastasis, but clinical data have been limited. As AC is commonly used in the prostate cancer population, the potential effect of AC on prostate cancer outcomes was examined using the Cancer of the Prostate Strategic Urological Research Endeavor (previous termCaPSURE)next term database.
Materials/Methods
The study comprised 5,295 men with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP, n = 3,523) or radiotherapy (RT, n = 1,772). of them, 1982 (37%) were receiving AC (warfarin, n = 428; clopidogrel, n = 287; enoxaparin, n = 26; aspirin, n = 1,649; combination, n = 408) at enrollment or during follow- up. Median age was 65, and median PSA was 6.0 ng/mL. The proportion of patients with low-, intermediate-, and high-risk disease was 41%, 37%, and 21%, respectively, according to NCCN criteria. Androgen deprivation therapy (ADT) was administered with RT in 28% of patients. The primary endpoint of the study was the risk of prostate cancer-specific mortality (PCSM).
Results
Compared to the AC group, the non-AC group was younger (median 64 vs. 66, p < 0.01) and more commonly treated with RP (69% vs. 62%, p < 0.01). PSA was slightly lower in the AC group (median 6.1 vs. 6.0, p < 0.01), but Gleason score (GS) and clinical T stage were similar. After a median follow-up of 59 months, PCSM was significantly reduced in the AC group, compared to the non-AC group (1% vs. 4% at 7 years and 4% vs. 10% at 10 years, p < 0.01). In a subgroup analysis by risk category, the reduction in PCSM was most prominent in patients with high-risk disease (2% vs. 8% at 7 years and 4% vs. 22% at 10 years, p < 0.01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the benefit of AC was primarily derived from aspirin. Multivariable analysis indicated that AC use was independently associated with a lower risk of PCSM (adjusted HR = 0.53, p < 0.01). Other significant variables included GS, utilization of salvage therapy, RT+/- ADT vs. RP, and statin use.
Conclusions
AC therapy, in particular aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The effect was most prominent in patients with high-risk disease. Further studies are necessary to elucidate the underlying mechanism for this effect, but it may be by suppressing metastasis.

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[Brim]

This type of data is hypothesis-generating only. Needs further study before an effect can be demonstrated.

Note that there has been some excitement over the years about the anti-cancer effect of cox-2 inhibitors such as celecoxib on various malignancies. Aspirin might do something similar. However, a few phase III trials on celecoxib have been published, and as far as I know, none have showed much benefit.

 

[Gfunk6]

I think this study is crippled by confounders. Obviously men in their mid-60's in the United States have serious cardiac risks across the population. Some of them have been fortunate to present with a "mini" MI or DVTs which necessitated the use of anti-coagulants which, I'm certain, decreased their future risk of cardiovascular mortality (that was the point of the intervention, afer all).

Some men, unfortunately, present with the "big one" (aka. deadly MI) and these men (obviously) don't get anti-coagulation.

So essentially you have old men with prostate cancer, half are treated with blood thinners the other half not. The ones that are have slightly reduced cardiac mortality. Well . . . duh

 

[radiation]

I would agree that there may be selection bias between the two groups as to who recieved aspirin, however the primary endpoint of the study was the risk of prostate cancer-specific mortality (PCSM), and not overall survival, so one would not expect cardiovascular mortality to account for the rather large differences in survival, particularly in high risk patients.

 

[Neuronix]

I would agree that there may be selection bias between the two groups as to who recieved aspirin, however the primary endpoint of the study was the risk of prostate cancer-specific mortality (PCSM), and not overall survival, so one would not expect cardiovascular mortality to account for the rather large differences in survival, particularly in high risk patients.

From that abstract there seems to be extreme and obvious selection bias here.

If the patients receiving aspirin or other anticoagulation are anticoagulated because of cardiac risk, they have an increased risk of death due to their cardiac problems. The patients without that cardiac co-morbidity are then free to die of other things, like prostate cancer. Hence the aspirin may seem protective of prostate cancer death, but the reality is that having heart disease means you die of the heart disease first and not cancer.

This is exactly why one would need a prospective randomized controlled trial to show this effect in order to change practices. Overall survival wouldn't necessarily be useful in this study because the group receiving anticoagulants is likely not as healthy as the other group. Unfortunately this not published work so it can not be analyzed further.

(Oral presentation at ASTRO it looks like. http://www.sciencedirect.com/scienc...7c8e8df86ee6c010e52f4dad18a4aa0a&searchtype=a)

 

[Charles_Carmichael]

This type of data is hypothesis-generating only. Needs further study before an effect can be demonstrated.

This is pretty much the problem with all retrospective studies isn't it? That they're really only good for hypothesis generation rather than providing conclusive evidence?

For example, there was a really interesting retrospective study regarding malignant gliomas (PMID: 20663133) recently but I'm not going to get excited until the results are validated in a prospective trial.

Edit: I pretty much agree with what Neuronix mentioned regarding the selection bias that seems to be going on in this study.

 

[medgator]

This is pretty much the problem with all retrospective studies isn't it? That they're really only good for hypothesis generation rather than providing conclusive evidence?

For example, there was a really interesting retrospective study regarding malignant gliomas (PMID: 20663133) recently but I'm not going to get excited until the results are validated in a prospective trial.

Edit: I pretty much agree with what Neuronix mentioned regarding the selection bias that seems to be going on in this study.

It'll be interesting if that glioma paper eventually causes our field to shift back towards WBRT...

 

[Charles_Carmichael]

It'll be interesting if that glioma paper eventually causes our field to shift back towards WBRT...

Aren't the fractions in WBRT still 1.8-2 Gy?

The authors of the study I cited hypothesize that because the SVZ is receiving subclinical fractions (~1.36 Gy), that it's not causing enough damage to stimulate the potent DNA damage response from the cancer stem cells. Thus, the cells are more likely to die. It's a cool concept that the CSCs might have a threshold amount of damage that needs to be reached before their DDR becomes fully activated, but there's not too much evidence behind this idea yet. But the paper definitely generated an interesting hypothesis and I hope it gets tested/validated in prospective trials as well as with bench work.

Edit: Sorry to the OP for derailing the thread a bit!

 

[medgator]

Aren't the fractions in WBRT still 1.8-2 Gy?

yeah they are. 45-50.4 Gy WBRT.

 

[subatomicdoc]

This type of data is hypothesis-generating only. Needs further study before an effect can be demonstrated.

Note that there has been some excitement over the years about the anti-cancer effect of cox-2 inhibitors such as celecoxib on various malignancies. Aspirin might do something similar. However, a few phase III trials on celecoxib have been published, and as far as I know, none have showed much benefit.

This isn't a first. Also has been interest in other cardiovascular drugs like statins. Too many confounding variables, lack of dose-duration data to make it more than an intellectual tease. Aspirin works differently the selective COX-2 but need prospective clinical data to 'prove' it.