# Prostate Cancer Aspirin has a more developed evidence base in **prostate cancer** than many readers realise. This is not just a prevention story. The literature also includes post-diagnosis survival data, a 2025 post-surgical recurrence study, and two biomarker-defined subgroups that may help explain why some studies look clearly supportive while others look neutral. [Read the summary](https://oncpracticemanagement.com/issues/2016/february-2016-vol-6-no-2/regular-aspirin-use-reduces-the-risk-for-prostate-cancer-death) That makes prostate cancer one of the more important aspirin pages outside colorectal cancer. ### Overview Prostate cancer is common, but not biologically uniform. Many cases are slow-growing. High-grade and metastatic disease is much more dangerous. Aspirin appears to matter most at the more aggressive end of the spectrum, where inflammation, **COX-2**, **TXA2**, androgen-signalling crosstalk, and metastatic biology become more relevant. [Read the 2025 paper](https://www.nature.com/articles/s41598-025-86521-x) This page matters because the signal is not only epidemiological. It also includes: * post-diagnosis mortality data * biochemical-recurrence data after surgery * subtype-specific molecular signals * direct tumour-tissue gene-expression findings in aspirin users ### Key human data #### Prevention Several prostate-cancer datasets support a preventive signal, especially for more aggressive disease. * **Physicians' Health Study:** In **22,071 men** followed for **27 years**, regular aspirin use at **three or more tablets per week** was associated with about **24% lower risk of lethal prostate cancer**. [Read the summary](https://oncpracticemanagement.com/issues/2016/february-2016-vol-6-no-2/regular-aspirin-use-reduces-the-risk-for-prostate-cancer-death) * **Population cohort with inflammatory-genotype signal:** Men using aspirin or ibuprofen at least **twice per week** for more than a month had about **33% lower prostate-cancer risk** overall. In men carrying the **LTA gene variant**, the reduction reached **57%**. Men without the variant did not show the same benefit. [Read the report](https://news.cancerconnect.com/an-aspirin-a-day-lowers-the-risk-of-cancer/) * **2025 Danish low-dose aspirin cohort:** Prostate cancer was among the tumour types showing lower risk with sustained long-term low-dose aspirin use. [Read the cohort paper](https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.35331) * **Meta-analyses:** Most summaries place the reduction in overall incidence somewhere in the **10% to 33%** range, with stronger protection often reported for more aggressive or lethal prostate cancer rather than indolent disease. [Read the review](https://pmc.ncbi.nlm.nih.gov/articles/PMC3526345/) That pattern matters. Aspirin may be less relevant to low-risk, slow-growing prostate cancer than to the inflammatory, high-grade, or metastatic end of the disease. #### Post-diagnosis survival This is where the literature becomes more interesting and more complicated. * **Physicians' Health Study, post-diagnosis analysis:** Regular aspirin use after diagnosis was associated with about **39% lower prostate-cancer-specific mortality**. [Read the summary](https://oncpracticemanagement.com/issues/2016/february-2016-vol-6-no-2/regular-aspirin-use-reduces-the-risk-for-prostate-cancer-death) * **Conflicting survivor cohort:** Another study of prostate-cancer survivors found **no significant association** between post-diagnosis aspirin use and lethal disease after adjusting for **Gleason score**, **stage**, and **treatment type**. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC3526345/) That conflict should not be hidden. It is one of the clearest examples in this section of why unselected populations can blur a real subgroup effect. #### Biochemical recurrence after radical prostatectomy The 2025 **Nature Scientific Reports** paper is one of the most clinically useful prostate-cancer aspirin datasets. It looked at men undergoing **robot-assisted radical prostatectomy**, or **RARP**, which is now a common surgical approach for localised disease. Aspirin users had better **biochemical recurrence-free survival** overall after surgery. [Read the paper](https://www.nature.com/articles/s41598-025-86521-x) The strongest signal was in high-risk disease. Men with **ISUP grade 4 or higher** showed hazard ratios of about **0.44 to 0.45**, which translates to roughly **55% to 56% lower risk of biochemical recurrence** compared with non-users. [Read the paper](https://www.nature.com/articles/s41598-025-86521-x) That is a striking result because the men with the most aggressive tumours appeared to benefit the most. ### Molecular biomarkers and subgroups #### LTA gene variant This is one of the more interesting biomarker stories in the aspirin literature. The **lymphotoxin-alpha**, or **LTA**, gene variant appears to define an aspirin-sensitive inflammatory subtype. In the reported cohort, men with this variant had about **57% lower prostate-cancer risk** with regular aspirin or ibuprofen use, while men without the variant did not show a significant benefit. [Read the report](https://news.cancerconnect.com/an-aspirin-a-day-lowers-the-risk-of-cancer/) This is not yet a clinical standard biomarker. But conceptually it is very important. It suggests prostate cancer may have an aspirin-sensitive molecular subgroup in the same way colorectal cancer has a **PIK3CA-selected** subgroup. #### TMPRSS2:ERG fusion The **TMPRSS2:ERG** gene fusion is present in about **half of prostate cancers** and is one of the most common molecular alterations in the disease. Prospective cohort work has suggested that aspirin use is associated with lower risk of **ERG-positive** prostate cancer specifically. That implies aspirin may act differently across molecular subtypes rather than affecting prostate cancer as a single category. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6170677/) This is still observational. But it is one of the strongest subtype-specific clues in prostate-cancer aspirin research. #### High ISUP grade disease The 2025 radical-prostatectomy study effectively adds another subgroup marker. Men with **ISUP grade 4 or higher** showed the clearest recurrence benefit after surgery. That makes high-grade disease one of the most practical current subgroups for aspirin discussion. [Read the paper](https://www.nature.com/articles/s41598-025-86521-x) ### Mechanistic relevance #### COX-2, PGE2, and androgen-receptor crosstalk One of the more prostate-specific aspirin mechanisms is the overlap between prostaglandin signalling and the **androgen receptor**, or **AR**. In prostate-cancer models, aspirin has been shown to increase **EP3 receptor** expression, which then helps suppress **AR** expression through **NF-κB-related** signalling changes. Lower AR signalling can reduce prostate-cancer-cell survival. [Read the mechanistic paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5359278/) That gives aspirin a biologically distinctive place in prostate cancer. It is not just an inflammation drug here. It also intersects with one of the main lineage-defining pathways of the tumour. #### TXA2 and platelet biology The thromboxane pathway is also highly relevant in prostate cancer. **TXA2 synthase** and the **thromboxane receptor**, or **TPr**, are elevated in malignant prostate cells compared with non-cancerous prostate cells. Their expression also correlates with **Gleason score** and **pathological stage**. [Read the paper](https://www.sciencedirect.com/science/article/abs/pii/S0302283806000959) That matters because prostate cancer often spreads to **lymph nodes** and **bone**, where platelet-assisted metastatic survival may become important. The 2025 **Nature** work on the **TXA2 → ARHGEF1 → CD8-positive T-cell suppression** axis gives this pathway more systemic meaning. [Read the Cambridge summary](https://www.cam.ac.uk/research/news/scientists-discover-how-aspirin-could-prevent-some-cancers-from-spreading) For the broader mechanism, see [Aspirin and Thromboxane A2 (TXA2)](/myhealingcommunity-docs/off-label-drugs-for-cancer/aspirin-in-oncology/anticancer-mechanisms/aspirin-and-thromboxane-a2-txa2.md). #### Gene-expression changes in human tumour tissue One of the most unusual prostate-cancer aspirin studies looked directly at gene expression in human prostate tumours from men who were regular aspirin users at diagnosis. Aspirin exposure was associated with measurable **ribosomal gene-expression changes** in tumour tissue, and the derived expression signature was linked to prognosis. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6298857/) This matters because it goes beyond lab models. It suggests aspirin can leave a measurable biological footprint inside actual human prostate tumours. #### NF-κB suppression and castration resistance **NF-κB** is constitutively active in **castration-resistant prostate cancer**, or **CRPC**, which is the more lethal and treatment-resistant state of the disease. Aspirin's ability to suppress **NF-κB** therefore remains highly relevant in advanced prostate-cancer biology, even though there is still no dedicated CRPC aspirin trial. [Read the mechanistic paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5359278/) ### Clinical positioning | Setting | Evidence | Position | | ---------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------- | --------------------------------------- | | **Prevention in general populations** | Repeated observational and meta-analytic signal, often strongest for lethal or high-grade disease. [Read the review](https://pmc.ncbi.nlm.nih.gov/articles/PMC3526345/) | Moderate and investigational | | **LTA-variant carriers** | Stronger genetic subgroup signal, with about **57%** lower risk. [Read the report](https://news.cancerconnect.com/an-aspirin-a-day-lowers-the-risk-of-cancer/) | Strong biomarker-level interest | | **Post-diagnosis mortality** | One major cohort shows a **39%** lower prostate-cancer-specific mortality signal, another is null. [Read the review](https://pmc.ncbi.nlm.nih.gov/articles/PMC3526345/) | Supportive, but clearly mixed | | **Biochemical recurrence after RARP** | Strong 2025 signal, especially in **ISUP grade 4 or higher** disease. [Read the paper](https://www.nature.com/articles/s41598-025-86521-x) | Most clinically specific recent dataset | | **TMPRSS2:ERG-positive disease** | Lower risk of ERG-positive cancer in prospective cohort data. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6170677/) | Important subtype clue | | **High-grade disease** | Clearer recurrence benefit after surgery. [Read the paper](https://www.nature.com/articles/s41598-025-86521-x) | Emerging precision subgroup | | **Castration-resistant prostate cancer** | Strong mechanistic rationale through **NF-κB** and AR-related biology. [Read the mechanistic paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5359278/) | Investigational only | ### Honest evidence assessment The prostate-cancer aspirin story is supportive, but not simple. The biggest tension is the survival literature. One major cohort suggests a real post-diagnosis mortality benefit. Another finds no clear effect after adjustment for grade, stage, and treatment. The most plausible explanation is not that one study must be wrong. The more plausible explanation is that aspirin benefit is **subgroup-dependent** and becomes diluted in unselected populations. The strongest candidate subgroups right now are: * men with **high-grade disease** * men with the **LTA inflammatory variant** * men with **TMPRSS2:ERG-positive** tumours * possibly men in the **post-prostatectomy recurrence-risk** setting That is what makes this page more advanced than it first appears. ### Practical interpretation For men with prostate cancer, the most useful questions are: 1. What was the tumour **ISUP / Gleason grade**, and was it **grade 4 or higher**? 2. Has the tumour been assessed for **TMPRSS2:ERG fusion**? 3. Is there access to **LTA variant** testing, or is that still research-only in this context? 4. Am I on **androgen-deprivation therapy**, and does aspirin's AR-related biology make the discussion more relevant? 5. Given cardiovascular benefit, GI risk, age, and bleeding risk, is **low-dose aspirin** a reasonable discussion with my treating team? That is the most honest way to use the current evidence. It is not a blanket prostate-cancer recommendation. It is a targeted, biology-aware discussion. ### References * *Nature Scientific Reports* 2025 — aspirin and biochemical recurrence-free survival after radical prostatectomy, strongest in **ISUP grade 4 or higher** disease. [Read the paper](https://www.nature.com/articles/s41598-025-86521-x) * Physicians' Health Study coverage — lower lethal prostate-cancer risk and lower post-diagnosis prostate-cancer mortality in regular aspirin users. [Read the summary](https://oncpracticemanagement.com/issues/2016/february-2016-vol-6-no-2/regular-aspirin-use-reduces-the-risk-for-prostate-cancer-death) * TMPRSS2:ERG subtype analysis — prospective cohort signal for lower risk of ERG-positive prostate cancer. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6170677/) * LTA-variant report — stronger risk reduction in the inflammatory-gene subgroup. [Read the report](https://news.cancerconnect.com/an-aspirin-a-day-lowers-the-risk-of-cancer/) * Mechanistic prostate-cancer paper — aspirin, **EP3**, **AR**, and **NF-κB** crosstalk. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5359278/) * Human tumour-tissue gene-expression study — ribosomal expression changes linked to aspirin use. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6298857/) * Null survivor-cohort analysis — no clear post-diagnosis effect after adjustment. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC3526345/) * Yang et al., *Nature* 2025 — platelet **TXA2**, immune escape, and metastatic spread. [Read the Cambridge summary](https://www.cam.ac.uk/research/news/scientists-discover-how-aspirin-could-prevent-some-cancers-from-spreading)

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