Risks of Prostate Cancer Among Patients With Rheumatoid Arthritis

Dr Austin Wheeler, from the University of Nebraska Medical Center, discusses research conducted to assess the risk of prostate cancer among patients with rheumatoid arthritis.

Austin Wheeler, MD, is a rheumatology fellow at the University of Nebraska Medical Center in Omaha, Nebraska.

TRANSCRIPT:

RALN:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw, and I'm here with Dr. Austin Wheeler, who's a rheumatology fellow at the University of Nebraska Medical Center. We're going to be discussing a study he participated in, prostate cancer among patients with rheumatoid arthritis. Thanks for joining us today, Dr. Wheeler.

Dr. Austin Wheeler:

Thank you so much for having me.

RALN:

Why did you decide to investigate this particular topic?

Dr. Austin Wheeler:

This idea of the relationship between RA and cancer is a really important topic for those of us who take care of people with RA and for our patients. So we already knew that patients with RA have an increased risk of lymphoma and lung cancer, but prostate cancer is the second most common malignancy in men, and it's the fifth leading cause of cancer death in men worldwide. Historically though, whether or not there's an increased risk in RA has been unclear, but we certainly know that there are certain biologic aspects of RA that are common to prostate cancer as well. And that's been really challenging to study in RA because most RA study cohorts are mostly made up of women. We're really well positioned within the VA because our study population is overwhelmingly male to study this so we had a large number of prostate cancer cases that we could compare.

So just to give you an idea, previously the largest study to look at this had about 19,000 participants, whereas we had about 280,000. There's also been this question of whether chronic diseases like prostate cancer might just be recognized more often in patients with RA because they're more frequently interacting with the healthcare system. And this was also really one of the first studies to evaluate that.

RALN:

That's very interesting. Can you tell us a little bit more about the study? Just give us a brief overview.

Dr. Austin Wheeler:

Yeah, of course. So this was a retrospective matched cohort study where we looked at the incidence of prostate cancer between men with and without RA. And so we had about 284,000 total and about 57,000 of those patients had RA. We used national VA data to identify patients with RA based on an algorithm with diagnostic codes, and then we matched each RA patient with up to 5 randomly selected people without RA, excluding anybody with a prior diagnosis of prostate cancer or a prostatectomy. And then we identified prostate cancer via linking our data with the VA cancer registry and the National Death Index. We did look at some covariates that are potential risk factors for prostate cancer, those being race, smoking status, Agent Orange exposure in the veteran population, amount of healthcare utilization... meaning number of outpatient visits in the prior year... BMI, comorbidities, and prior screening for prostate cancer.

And then we followed the patients until they had either a diagnosis of prostate cancer, death, or the end of the study period. And then we used all of that to calculate prostate cancer incidents and mortality rates and then we calculated prostate cancer hazard ratios for patients with and without RA including when we accounted for the other risk factors. And then the last thing we did touches on that relationship of healthcare system exposure where we looked at whether increased exposure to the healthcare system for RA patients might cause them to be diagnosed more with prostate cancers. So for this, we censored out patients that had more than a year between their VA healthcare encounters and we generated survival curves for survival free of prostate cancer and prostate cancer death with and without RA to compare the overall cohort with the cohort adjusted for healthcare exposures.

RALN:

I guess we could fairly call this a pretty comprehensive study. What was that period that you tracked these patients through?

Dr. Austin Wheeler:

So we tracked these patients over a period of several years. The initial matching was actually January 1st, 2000, and then the final date was December 31st, 2018, so that's a period of 18 years that we followed these patients.

RALN:

And what did you find?

Dr. Austin Wheeler:

Well, first we saw about 1400 prostate cancers in the RA patients and about 5,000 in the non RA patients. When we looked at incidents rates we saw an incident rate of 3.5 per 1000 patient years in the RA patients as compared to 2.7 in the non RA patients. After we censored out patients that had more than a year without healthcare exposure, the incidence rates were 3.7 in RA and 2.9 in non RA. Most of those cancers were stage 2 prostate cancer and we didn't see any difference between RA and non RA patients in cancer stage at diagnosis. And then the mortality rates for prostate cancer were 0.37 per 1000 patient years in the RA group and 0.42 in the non RA group, and that was not affected by censoring for healthcare exposure. And then when we matched patients with RA to those without we saw that RA was associated with a significantly higher risk of prostate cancer and the hazard ratio for that was 1.28.

When we adjusted for those other risk factors that I mentioned, that did decrease to 1.14. And then when we further censored for health care exposure it decreased down to 1.12, but it was still significantly more in the RA patients. And then we used a statistical measure called an evalue, and what we found with that was that only minimal unmeasured confounding factors would explain away that association of RA with prostate cancer. And then we also saw that RA was not associated with an increase in prostate cancer death, and that was unchanged by any of our adjustment or censoring.

So I guess in summary of all that, it looked like RA patients seem to have a modest increase in their risk of prostate cancer but no increased risk of death from prostate cancer. And since we showed that it would take only minimal confounding to explain that away, it seems unlikely that RA causes an increased prostate cancer risk. Finally, the increased healthcare exposure associated with RA does impact the detection of prostate cancer. And so we feel that it needs to be considered as a potential source of bias in other studies looking at health outcomes in RA.

RALN:

What do you know about why patients with RA seem to have this increased risk of other types of cancer such as lymphoma and lung cancer? What have we found out about that?

Dr. Austin Wheeler:

Yeah, this is a big area of interest. We don't have a really clear explanation of why that is, but there are a variety of things that have been proposed. So for lymphoma, there's been this thought that ongoing immunologic stimulation from chronic inflammation in RA could kind of predispose folks to that. In lung cancer, it's probably more of a component of just chronic lung inflammation. I mean, there are also shared risk factors like smoking for instance, but that risk with lung cancer is still increased even in non-smokers with RA. So there has been some prior evidence to support that the lung mucosa itself actually acts as an area of immune activation in RA, so that could be a potential way to link those together. But this is definitely an area that is in need of more research for us to fully understand that association.

RALN:

Are there specific types of cancer screening that patients with RA, male or female, should be receiving due to this known additional risk of developing certain types of cancer?

Dr. Austin Wheeler:

The screening recommendations for cancer in RA patients are the same as the general population, which includes lung cancer, colorectal cancer, prostate cancer. So there's no specific recommendations that are different than kind of our standard population. For prostate cancer the USPSTF recommendations are to discuss risks and harms of PSA based screening with patients age 55 to 69. The American Cancer Society recommends discussing screening with men over 50 with at least a 10-year life expectancy, or men over 45 at high risk, or men over 40 who have more than one first degree relative with early prostate cancer. We really just kind of abide by those. And that screening is done, again, with a PSA blood test.

RALN:

Does a personal or family history of cancer have any effect on decisions about the kinds of therapies that should be prescribed for patients with RA?

Dr. Austin Wheeler:

We didn't have any data on family history in this study, which is important to point out. The impact of therapies for RA is definitely something that has been a concern for patients and for providers as well. And so, I mean in general, it's important for rheumatologists to discuss the risk and benefits of any therapy before starting a new medication. And for many of our therapies in RA that does include a discussion of cancer risk.

RALN:

What would you advise rheumatologists to be conscious of when they are working with these patients who have RA regarding early signs and symptoms of cancer? What should they be on the lookout for?

Dr. Austin Wheeler:

So I think we just need to be really vigilant in evaluating our RA patients for possible malignancy. We have to ask about symptoms, do a comprehensive review of symptoms at every visit because they otherwise might not volunteer symptoms that they don't necessarily think are relevant for their RA. And then collaborating with primary care. We see our patients really frequently for management of RA, often more frequently than their primary care physician, so we have an opportunity to catch these things earlier if we're asking the right questions and letting the patients kind of give us those early symptoms.

In general, we have a really good relationship with our patients and so we could also leverage that to help with modifiable risk factors for cancer. And the most important of those would be smoking cessation. And so it's responsibility to counsel on smoking cessation. We can all step up to help with that. And even on top of that, there may be an opportunity when our patients are doing well from an RA standpoint for us to double check whether they're up-to-date on lung cancer screening or even initiate that conversation about prostate cancer screening and loop in their primary care providers with that conversation.

RALN:

Any further advice for your colleagues who treat patients with rheumatoid arthritis?

Dr. Austin Wheeler:

Well, I think overall we can feel reassured by the findings from this study that there's not a markedly increased risk of prostate cancer in our RA patients. That being said, because prostate cancer is such a common cancer among men in general, we should encourage them to get their regular cancer screenings. We as rheumatologists can utilize the trust from our patient-physician relationships to help encourage our patients to get these really important and valuable screening tests.

RALN:

Thanks very much for spending this time with us. This is an interesting study and we'll look forward to catching up with you later. Thank you.

Dr. Austin Wheeler:

Thank you so much.