10-year survival of conservatively managed prostate cancer patients with T1/T2 disease

Yet another study has added to the available data on the potential of conservative management for newly diagnosed prostate cancer patients. The current study reflects experience most specifically with the management of men of ≥ 65 years of age.

The article, appearing this week in the Journal of the American Medical Association, is another restrospective analysis of data by Grace Yu-Lao and colleagues. The goal of the researchers was to evaluate the outcomes of patients with clinically localized prostate cancer managed without any immediate attempt at curative therapy in the PSA era.

Yu-Lao et al. examined data from a population-based cohort of men aged 65 years or older and diagnosed with stage T1 or T2 prostate cancer between 1992 and 2002. All patients were managed without surgery or radiation for at least 6 months after diagnosis. The patients, all of whom lived in areas covered by the Surveillance, Epidemiology, and End Results (SEER) program, were followed up for a median of 8.3 years (through December 31, 2007). Competing risk analyses were performed to assess their outcomes.

The results of the study may be summarized as follows:

  • The median age of  the men was 78 years at cancer diagnosis.
  • 10-year prostate cancer-specific mortality was 8.3 percent for men with well-differentiated tumors; 9.1 percent  for those with moderately differentiated tumors, and 25.6 percent for those with poorly differentiated tumors.
  • The corresponding 10-year risks of dying of competing causes were 59.8, 57.2, and 56.5 percent, respectively.
  • The 10-year disease-specific mortality for men aged 66 to 74 years diagnosed with moderately differentiated disease was 60 to 74 percent lower than in earlier studies:
    • 6 percent in the contemporary PSA era (1992-2002)
    • 15 to 23 percent in earlier eras (1949-1992).
  • Improved survival was also observed in poorly differentiated disease.
  • The use of chemotherapy (in 1.6 percent of patients) or major interventions for spinal cord compression (in 0.9 percent of patients) was uncommon.

It is hard to know exactly how to interpret some of the data in this study.

Clearly, patients with clinically localized prostate cancer diagnosed between 1992 and 2002 and given initial conservative management had notably better than outcomes than comparable patients diagnosed in the 1970s and 1980s. However, it is less clear why this should be the case. We know that PSA testing introduced what is known as stage shifting and “lead time bias.” In other words, the men were getting diagnosed earlier than they might have without the existence of the PSA test. We also know that many of these men might never have been diagnosed at all in the pre-PSA era. And many physicians believe that advances in medical care also have an impact on the prevention of death from prostate cancer.

The “New” Prostate Cancer InfoLink takes the position that the exact reason for this decline in risk for prostate cancer-specific mortality is less important than the fact that it has happened. It would seem to be apparent that we are reducing the numbers of men who have (and therefore have to be treated for) the most serious consequences of metastatic prostate cancer. We have succeeded in this because we are cognizant of their risk as opposed to ignoring it. And this appears to be the case even for those men who are managed under conservative, expectant management protocols.

It is certainly true that the average age of these men at the time of diagnosis was high (at a median of 78 years), and that conservative management might be less appropriate for selected men who have a high life expectancy and who were in the younger range of patients even in this study, but let’s not discount the good news: our ability to manage men with prostate cancer seems to be improving — even under expectant management.

4 Responses

  1. Amazing Grace!

    Selecting a cohort of men with a median age of 78 to prove a point is highly suspicious in my view…

    What is new here? In the past, Grace Lu-Yao has reported data from other large population studies (see, for example, Lu-Yao G et al., Population-based study of long-term survival in patients with clinically localised prostate cancer. The Lancet. 349: 906-910, March 20, 1997) in which the authors reported the percentages of patients diagnosed with localized who had 10-year disease-specific survival by grade and by treatment type as follows:

    Gleason grade 2-4 (n = 20,500): radical prostatectomy, 94%; radiation therapy, 90%; conservative therapy, 93%
    Gleason grade 5-7 (n = 12,700): radical prostatectomy, 87%; radiation therapy, 76%; conservative therapy, 77%
    Gleason grade 8-10 (n = 19,900): radical prostatectomy, 67%; radiation therapy, 53%; conservative therapy, 45%

    A study by Gronberg et al. in 1994 demonstrated the importance of age and disease grade at diagnosis and loss of life from prostate cancer — typically claimed to be an indolent disease (see Gronberg H et al., Patient age as a prognostic factor in prostate cancer. J Urol., 152: 892-895, 1994). The study clearly showed that younger patients with higher grade disease “lost more life” as a consequence of their cancer than older patients with lower grade disease.

    It is obvious that if you are at or above age 70 and diagnosed with low grade cancer, you have the option to do nothing with the understanding that you have a possibility of only losing 20% of your remaining expected life. However, the same man with high grade cancer can lose 63% of his expected life. Big difference!

    At younger ages, the higher cancer grade produces a greater life loss. If the majority of disease is diagnosed with higher grades of cancer, and there is considerable survival benefit to aggressive treatment versus conservative management, why not take advantage of early diagnosis to shift the diagnosis stage to a lower grade disease? To ignore all these facts and to assume that early detection is equal to over-treatment is misleading. It is claimed that most men these days are diagnosed with insignificant disease. If such is the case, most men should undergo active surveillance for a period to determine their potential risk of perishing from the disease. Urology should concentrate in resolving the over-treatment claim by establishing clear clinical practice guidelines. Age and grade at diagnosis are relevant and should not be ignored. Better understanding of disease progression and quality of life issues is needed.

  2. Dear Ralph:

    I have a completely different take on the recent study by Grace Lu-Yao — which is that she has absolutely proved your point: early detection is good because it permits appropriate treatment (including conservative treatment for those at least risk of clinically significant disease). This is not “new” to you (or to me), but it is “new” to an awful lost of people who haven’t been looking at this as long as you and I have. This study actually proves the value of early detection in men older than 60 years of age while simultaneously pointing out that immediate treatment is unnecessary in a very high percentage of these patients — most particularly those with low grade and low-risk disease who are over about 75 years of age and have a life expectancy of 10 years or less. Do we need a similar data analysis for men diagnosed at less than 60 years of age? Yes we do!

    I would also point out that Dr. Lu-Yao did not “select” a cohort of men with a median age of 78. She selected all men over 60, which is, after all, a very high proportion of the men diagnosed with prostate cancer in any one year. These men happened to have a median age of 78 years. That’s not Dr. Lu-Yao’s fault!

  3. Dear Mike,

    The problem is that with that high median age most men die of something else and this supports the indolence of prostate cancer. Early detection is a reasonable activity, but those that say that it creates much over-treatment are set and determined to negate its value and bring us back to the Stone Age when most men were diagnosed too late.

    As you can see from the Gronberg study prostate cancer has quite a loss of life …

  4. Ralph: I agree with you 100% … but that doesn’t mean that Lu-Yao’s data aren’t important. The fact that people interpret data to prove a point as opposed to simply accepting the data for what they are cannot be blamed on the creators of the data!

    Lu-Yao et al.’s data can be interpreted in several ways — one of these is that early detection makes it possible for men to determine if and when they need invasive treatment, as opposed to simply rushing into to it too early or getting diagnosed too late to benefit from curative treatment at all.

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