Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced PCa

Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer: A Systematic Review and Meta-analysis (2022, Full Text)

Hyperlink not working; for Full Text, copy and paste link:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799080

(Dr. Laurence Klotz is a coauthor of this JAMA study in pre-print)

"KEY POINTS

Question Is statin use during androgen-ablative therapies (androgen deprivation or androgen receptor axis–targeted therapies) associated with reduced mortality among men with prostate cancer?

Findings In this systematic review and meta-analysis of 25 cohorts including 119 878 men, concurrent statin use was associated with a 27% reduced risk of overall mortality and a 35% reduced risk of prostate cancer–specific mortality.

Meaning These findings suggest that concurrent statin use may improve survival in men receiving androgen-ablative therapies for advanced prostate cancer; randomized clinical trials are warranted to confirm these findings.

ABSTRACT

Importance Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.

Objective To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis–targeted therapies (ARATs).

Data Sources This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022.

Study Selection Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).

Data Extraction and Synthesis Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Main Outcomes and Measures Overall mortality and prostate cancer–specific mortality (PCSM).

Results Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes.

Conclusions and Relevance The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results."

From the Full Text:

"Our study represents, to our knowledge, the most comprehensive summary to date on the associations between statin therapy, androgen-ablative therapy, and prostate cancer. We observed a consistent overall and prostate cancer–specific survival advantage for statin users undergoing androgen-ablative therapies, independent of patient age, baseline metastasis status, prior use of chemotherapy, or primary treatment type. For overall mortality, the observed benefit was independent of hormone sensitivity status and type of androgen-ablative therapy. Conversely for PCSM, there was an incremental advantage of statins for men receiving ARATs compared with men receiving ADT."
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(All emphasis mine. See the Full Text for discussion)

Although the findings are limited by the type of study to only an association between statin use and reduced mortality, IMO a "chicken soup" approach seems wise. Note that statin use usually requires periodic liver-function testing

Djin

Duck2 said...
Djin,

This is the second study I have read on this. The first was one VA patients. Both indicate an improvement.

Indeed, some evidence has been gathering, and it has been getting stronger. As the following recent, disappointing study points out, we'd like to know which categories of men benefit. Knowing that, we might get at the mechanism of action, which, one hopes could be parlayed into even better drugs. Repurposing medications is a hot topic in itself, BTW.

Impact of Statin Use on Localized Prostate Cancer Outcomes after Radiation Therapy: Long-Term Follow-Up (2022, Full Text)

"Simple Summary
Statins represent a promising class of agents to improve clinical outcomes of prostate cancer patients treated with radiotherapy, but the results of numerous studies are contradictory. We aimed to assess the impact of statin use on biochemical recurrence in a large database of patients of different risk groups undergoing different modalities of radiation therapy. We evaluated 3555 patients treated with curative external beam radiotherapy, low-dose-rate seed brachytherapy, or external beam radiotherapy plus high-dose-rate brachytherapy. We found no improvement in biochemical recurrence-free survival in statin users, regardless of radiotherapy modality. Our study underlines the need to search for biomarkers that predict an additive effect of statins and determine which patients treated with radiotherapy may benefit from statins as an anticancer drug.

Abstract
The impact of statin use on localized prostate cancer (PCa) remains controversial, especially for patients treated with radiation therapy. We assessed the impact of statin use on biochemical recurrence (BCR) in patients treated for PCa with different modalities of radiation therapy. We evaluated 3555 patients undergoing radiation therapy between January 2001 and January 2022. The impact of statin use on BCR was analyzed for three treatment groups: external beam radiotherapy (EBRT), low-dose-rate seed brachytherapy (LDR), and EBRT plus high-dose-rate brachytherapy (EBRT + HDR). Median follow-up was 52 months among 1208 patients treated with EBRT, 1679 patients treated with LDR, and 599 patients treated with EBRT + HDR. A total of 1544 (43%) patients were taking a statin at the time of treatment, and 497 (14%) patients were in the D’Amico high-risk group. Only intermediate-risk patients treated with LDR fared better with statin use in univariate analysis (p = 0.025). This association was not significant in multivariate analysis (HR 0.44, 95% CI 0.18–1.10, p = 0.06). Statin use was not associated with a reduced risk of BCR in patients treated with radiation therapy. In the era of precision medicine, further investigation is needed to assess the benefit of statins in well-defined patients."
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Note, however, that BCR is quite a poor stand-in for overall survival. However, it's handy and it's used because otherwise you have to conduct follow-up studies for decades. In other words, even if these results are confirmed in other studies, it doesn't rule out a beneficial effect of statins on overall or cancer-free survival in these men.

Post Edited (DjinTonic) : 12/2/2022 12:05:28 PM (GMT-8)

compiler said...
Does the article indicate the dosage?
I am on 10 mg and my wife is on 80 mg.

(It works wonders for her-- heh heh).

Mine was for slightly high cholesterol (about 230 or so when prescribed -- about 165 while on the drug). I get the feeling Dr. Lam would prescribe it if I wasn't on it.

Mel

From the Full Text:

'Dose-Response Analysis
A dose-response analysis was planned a priori; however, because insufficient data were available for meta-analysis, only a systematic review was reported. Similarly, analyses of statin class (hydrophilic vs lipophilic) were precluded by limited data availability."

Djin:

Thanks again for all the fine research you do.

Mel