Review of the medical literature —Mortality of Untreated Prostate Cancer.
Prostate cancer mortality before the PSA era. Why is the USPSTF ignoring this data? Should men ignore this data?
Contrary of what we currently hear, without early detection by PSA testing, prostate cancer is diagnosed at advanced stages that increase the risk of dying of the disease. This is the current situation on countries in which the use of PSA is very low. In countries in which PSA use is high, PCa mortality has been reduced. In such countries, those opposed to the use of PSA point to excessive over treatment. No question that over treatment exists and should be avoided. One way of doing this is applying active surveillance more often in cases of low-grade cancers as defined by the various current protocols and learn from that experience.
The amount of over treatment is in question. Computer models report a range of over diagnosis and over treatment of 25% to 85% depending on definition. In the Tyrol, Austria study where every patient diagnosed was treated, only 8.7% were over treated. This is actual data from an ongoing study and...not computer generated estimate. Before the introduction of the PSA test 75% of patients were diagnosed with symptoms of advanced disease and proportionally more men died of the disease.
What follows are selections from various sources related to the mortality of untreated prostate cancer:
1. Prostate cancer mortality was 80% in men younger than 60 years, 63% in men 60-69 years old, 53% in men 70-79 years old and 49% in men older than 80 years.
Damber JE, Grönberg H .Mortality due to prostatic carcinoma in northern Sweden. : Urologe A. 1996 Nov;35(6):443-5
2. Survival rates were adjusted for expected mortality in the general population and were expressed as relative survival (RS). RS for the total cohort after 5, 10 and 20 years was 51, 34 and 17% respectively, with an annual excess death rate of about 8% which persisted also after long-term observation. RS was similar in age groups between 45 and 74 years, whereas among patients older than 74 years at diagnosis approximately 10% lower RS appeared early and was persistent. RS improved for patients diagnosed at consecutive 5-year periods. Thus, the high mortality rate in old age groups and the low long-term RS contradicted the concept that biologically inactive tumours constitute a significant proportion of prostatic cancers diagnosed in clinical practice.
Norlén BJ. Survival and mortality in prostatic cancer. A study based on the Swedish Cancer Register. Acta Oncol. 1991;30(2):141-4.
3. RESULTS: Overall, 62% of patients with a known diagnosis of PC died of the
disease when all patients were followed from diagnosis until death (up to 25 years). Of patients in stage M0 at diagnosis, 50% died of PC. However, in patients who survived for more than 10 years the mortality reached 63%
Aus G .Prostate cancer. Mortality and morbidity after non-curative treatment with
aspects on diagnosis and treatment.
Scand J Urol Nephrol Suppl. 1994;167:1-41.
4. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50%. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.
Hugosson J, Aus G. Natural course of localized prostate cancer. a personal view with a review of published papers. Anticancer Res. 1997 May-Jun;17(3A):1441-8.
5. RESULTS: The study population was composed of 6514 patients diagnosed with prostate cancer during 1971 to 1987 in northern Sweden.
about 85% of these patients died during the 7 to 23 years of follow-up, and the
prostate cancer-specific mortality was estimated to be 55%. Age at diagnosis was
found to be a strong predictor of prostate cancer death. Patients diagnosed before the age of 60 had an 80% risk of dying of prostate cancer, whereas those over 80 years of age at diagnosis had less than a 50% risk of prostate cancer-related death.
Grönberg H, Damber L, Jonson H, Damber JE. Prostate cancer mortality in northern Sweden, with special reference to tumor grade and patient age.Urology. 1997 Mar;49(3):374-8.
6. The long-term outcome in patients with prostate cancer treated with palliative
intent was examined in two populations from Göteborg, Sweden. The results showed a prostate-cancer-related mortality of 62%. The cumulative mortality increased over time, indicating that prostate cancer may be a slow-growing tumour, but that patients were at considerable risk for disease progression and eventual death. Dying from prostate cancer was associated with a long hospital stay and frequent demands for palliative treatments such as TURP, radiation and procedures due to upper-urinary-tract obstruction. In a subpopulation of patients who survived for more than 10 years, the cancer-related mortality was surprisingly high, 62% after noncurative treatment. Even if the patients were diagnosed before the PSA era, the above findings should be taken into account when advising patients with prostate cancer about therapy if they have a long life expectancy.
Aus G, Hugosson J. [Non-curative treatment of prostate carcinoma. Outcome in
Göteborg]. Urologe A. 1996 Nov;35(6):449-53.
7. RESULTS: The total number of 719 new cases of prostate cancer were diagnosed without any screening programs. Forty-five percent of patients were diagnosed incidentally, and 31% of all patients had organ-confined disease (T1a-T2, Nx, M0). The disease specific survival rates at 1, 5, and 10 years were 80%, 38%, and 17%, respectively, and 62% of the patients died primarily of prostate carcinoma. A multivariate analysis demonstrated a statistically significant relationship between disease specific death and T classification, tumor differentiation, and erythrocyte sedimentation rate at diagnosis.
CONCLUSIONS: Prostate carcinoma patients have a poor survival and the majority of the patients diagnosed suffer and die from their disease rather than with it. Nevertheless, approximately one-third of patients neither suffer nor die from their disease. Therefore, the development of prognostic markers to improve the identification of patients who will benefit from early aggressive treatment is important.
Borre M, Nerstrøm B, Overgaard J. The natural history of prostate carcinoma based on a Danish population treated with no intent to cure .Cancer. 1997 Sep 1;80(5):917-28.
8. Computerized linkage between the Danish Cancer Registry and the Central Personal Registry was established. A total of 1459 men aged 55-74 years with newly diagnosed clinically localized prostate cancer in the period 1983-1987 were identified. Routine treatment in this period was observation and endocrine therapy in case of progression. Survival analysis demonstrated a significant excess mortality and a substantial loss of life expectancy.
Brasso K, Friis S, Juel K, Jørgensen T, Iversen P. [Localized prostatic cancer. Survival and loss of life expectancy].Ugeskr Laeger. 1998 Jul 27;160(31):4517-20.
9. Prostate cancer mortality in Norway is the highest among the Nordic countries and among the highest in the world. Five-year relative survival for all cases combined is 60%. Approximately 55-60% of the patients die from the disease.
Harvei S. [Epidemiology of prostatic cancer]. Tidsskr Nor Laegeforen. 1999 Oct
10. CONCLUSIONS: The disease-specific mortality was comparatively high, but it took 15 years to reach a disease-specific mortality rate of 56%. These data form a truly population-based baseline on how prostate carcinoma will affect a population when screening is not applied and can be used for comparison with other health care strategies.
Aus G, Robinson D, Rosell J, Sandblom G, Varenhorst E; South-East Region Prostate Cancer Group. Survival in prostate carcinoma--outcomes from a prospective, population-based cohort of 8887 men with up to 15 years of follow-up: results from three countries in the population-based National Prostate Cancer Registry of Sweden. Cancer. 2005 Mar 1;103(5):943-51.
11. Most cancers had an indolent course during the first 10 to 15 years. However,
further follow-up from 15 (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0% to 36.0%), survival without metastases (from 76.9% to 51.2%), and prostate cancer-specific survival (from 78.7% to 54.4%). The prostate cancer mortality rate increased from 15 per 1000 person-years (95% confidence interval, 10-21) during the first 15 years to 44 per 1000 person-years (95% confidence interval, 22-88) beyond 15 years of follow-up (P =.01).
CONCLUSION: Although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. These findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years.
Johansson JE, Andrén O, Andersson SO, Dickman PW, Holmberg L, Magnuson A,
Adami HO. Natural history of early, localized prostate cancer. JAMA. 2004 Jun 9;291(22):271
Bottom line: The USPSTF’s recommendation as it stands will cause a reduction in
PSA testing. This reduction will increase the number of men diagnosed with
advanced disease and increase the number of PCa deaths. As PCa survivors will we allow that to happen? When the same panel tried the this strategy with breast cancer screening, women raised their concerns and the USPSTF backed off. We need to do the same. I would not be here today if not for the PSA test. It gave me the information needed to decide on treatment that ultimately prolonged my life. I am only a point in the PSA curve reducing prostate cancer deaths and that is motivation enough for me to be proactive on this issue.
DISCLAIMER: I am a prostate cancer survivor since 1992. The views or opinions expressed here are my own and are not endorsed nor supported by any agency or institution. Recommendations SHOULD NOT be construed as professional advice.
DX at age 58. RP; Orchiectomy; GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall; Stage T4; Last PSA July, 0'11: <0.1ng/ml