What did the patient actually die of?

Two questions that come up regularly are whether: (a) men who are said to have died of prostate cancer actually did, and (b) men with prostate cancer who are said to have died of something else actually died of their prostate cancer.

A study carried out between 2009 and 2014 in the county of Vestfold in Norway has provided us with some insights into this quandary. (Vestfold is one of the smallest counties in Norway and is just south of the capital city of Oslo.) The study by Löffeler et al. has just been published in the Scandinavian Journal of Urology.

Löffeler and his colleagues set out to validate the accuracy of whether, between 2009 and 2014, a cohort of 764 men had actually died of prostate cancer or not. The cohort included:

  • 328 men who had been recorded as having died of prostate cancer on Part I of their death certificates (Group A)
  • 126 men who had prostate cancer listed as a significant condition on Part II of their death certificates, but whose cause of death was given as something else (Group B)
  • 310 men who had been diagnosed with prostate cancer but for whom there was no mention of prostate cancer in their death certificates

The research team first did everything they could to establish the true cause of death of each of these 764 men through careful scrutiny of their medical records and other available records. They then compared their findings to the actual death records available through the Norwegian Institute of Public Health and the Norwegian Cancer Registry.

Here is what they found:

  • Among men in Group A, prostate cancer-specific deaths were over-reported by 33 percent. In other words, 108/328 men in Group A did not actually die of their prostate cancer.
  • Among men in Group B, prostate cancer-specific deaths were under-reported by 19 percent. In other words, there had really been 24 men who died of prostate cancer in Group B.
  • Among men in Group C, prostate cancer-specific deaths were under-reported by 5 percent. In other words, there had really been 16 men in Group C who died of prostate cancer.
  • The correlation between registered and actual causes of death was only 0.81. In other words, it was wrong about 19 percent of the time.
  • Misattribution of prostate cancer as a cause of death among men known to have prostate cancer at the time of their death increased significantly with patient age and with decreasing Gleason score.

Löffeler et al. go on to explain that:

  • Prostate cancer-specific mortality data in Vestfold seem to be relatively accurate for men aged < 75 years at the time of their deaths.
  • The overall accuracy of cause of death assignment in Vestfold was significantly reduced by misattribution of prostate cancer as a cause of death among men of > 75 years (and such men represent the large majority of prostate cancer deaths).
  • Over-reporting of prostate cancer as a cause of death among elderly men may affect prostate cancer mortality data in countries other than Norway.

True 100 percent accuracy in the assignment of the cause of death for a specific person can be hard even when an autopsy is carried out. Without an autopsy, it is near to impossible for many older men who may have multiple co-morbid conditions. Furthermore, for a man who had died of or with prostate cancer in his 80s, the assignment of the cause of his death is often made by a primary care doctor who comes to his home or by a primary care physician at a local hospital as opposed to the doctor who has been treating him for his prostate cancer. Autopsies are rarely carried out on men of > 75 years of age unless there is some good reason to suspect a problem. And of course most men who live to > 75 years of age have at least one other co-morbid condition on top of whatever may have led to their death.

The bottom line is that assignment of actual causes of death for men with prostate cancer are difficult to validate with accuracy. And in many cases the cause of death may be a judgment call anyway. Did the elderly patient with metastatic, castration-resistant prostate cancer who died of pneumonia actually die of pneumonia? Or did he catch the pneumonia as a consequence of being immune-suppressed from treatment for his prostate cancer such that he was unable to fight off the pneumonia?

4 Responses

  1. Excellent study and excellent analysis by Sitemaster! Spot-on analysis including pneumonia example.

    As a healthcare actuary, I’ve tried to analyze prostate cancer cause of death reporting accuracy and have discussed it with an acquaintance and US government analyst whose department tracks causes of death.

    The “cause” of death is an extremely murky area and varies a great deal from one location to another. What is the primary cause vs. secondary cause, etc.?

    I understand that in the US, the person putting down the cause often has a few boxes to check on a standard form, and prostate cancer is not one of them. The young Resident filling out the form may not even know details about the patient’s background, and he has an endless list of important things that he must complete that day.

    If a cardiac patient’s heart stops, it might erroneously be assumed to be heart problem, not complications caused by ADT. I’d say cancer. Also, let’s say there is a prostatectomy and the patient dies within 30 days from complications, do you think that Resident filling out the cause of death always puts down complication from surgery? Maybe … but he may not be comfortable attributing it to his employer or boss.

    Does the cause matter? Yes, it affects how much funding goes to prostate cancer research. And it affects how we judge safety and effectiveness.

    So much thanks to you for covering this.

  2. This is a familiar issue to me and has been for some time; sadly, I encounter it regularly in the US. Men with late stage prostate cancer who have been fighting the disease for several years may finally pass from infection, pneumonia, or similar. Their death is not attributed to prostate cancer.

    Hard to tell the epidemiological significance since this Norwegian study suggests it cuts both ways. Anecdotally, I have seen prostate cancer as cause of death understated. Is anyone aware of any US work on this issue?

  3. I love this post sitemaster. It was a topic at our UsTOO group I addressed tonight. I put a couple of anecdotes out there for a reason.

    Dennis Hopper’s death certificate was posted morbidly online shortly after his death. And I morbidly found it. His primary cause of death was hepatic failure. His secondary or contributing cause of death was prostate cancer on that certificate.

    My second case was a known musician who became my friend. He was 42 and died at 46 of liver failure. And it remains consistent in my experiences as a researcher with a patient representative’s perspective.

    There are two well known causes of this. Prostate cancer that can inundate skeletal frame or vital organs. And then there’s treatments meant to stop or slow it. In a cancer survivorship research committee I observe, and this involves many different adult cancers, it’s well known that a treatment can in fact lead to a cause of mortality. But many times it can improve quality of life while extending it. But the drugs or combinations used can still be the cause of overall mortality.

  4. This has always been a quandary. I have been able to manage and control my continuing prostate cancer with ADT for over 21 years since its recurrence in 1996 following obvious failed surgical removal of the gland and salvage radiation to the prostatic bed and its periphery in 1992/early 1993.

    It is still playing its game within me with a PSA level last week of 1.09 ng/ml while on Lupron, Avodart, Xtandi, metformin, vitamin B12 (because of the Metformin), and Prolia as a safeguard for bone issues. I am experiencing no pain, feel quite healthy other than having experienced “possible” TIA issues twice last year, and pulmonary embolisms to both lungs once in 2010 and once in 2012 (now that was scary), and as the result of ADT medications and those issues, regular continued fatigue, weakness, and some “balance” issues.

    At my current age of 85, should I suddenly die, I suspect I will be one of those written off as “age-related complications.” I do suspect that with prostate cancer our disease can contribute to the weakening of other organs in our system even without actual metastases to those organs, and — that being the case — should any other organ or organs end up being considered the cause of our demise, prostate cancer will not be mentioned as contributing to that demise.

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