A new article in European Urology offers interesting data on the natural history of localized prostate cancer, based on a cohort of 200+ Swedish patients followed for > 30 years. It is important to note immediately that none of these men was originally diagnosed in the PSA era. They all had some form of symptomatic disease at diagnosis.
There has been a real shortage of information about the long-term impact of managing men with low-risk, early stage prostate cancer by any form of observation/monitoring as opposed to early active treatment, even though it is well understood that a significant percentage of localized, early-stage prostate cancer do have an indolent course. We also know that, within 15 years from time of diagnosis with localized prostate cancer, most deaths of men so diagnosed are not prostate cancer-specific, but are a consequence of a wide variety of other age- and health-related factors.
Popiolek et al. have now published data from a series of 223 consecutive patients, all from a regionally-define area of central Sweden, initially diagnosed with localized prostate cancer, initially managed by observation rather than any form of active intervention, and treated with androgen deprivation therapy (ADT) when symptomatic tumor progression became evident.
Here are the core findings of their study after 32 years of follow-up:
- 220/223 men in the study (98.6 percent) had died.
- 90/223 men (41.4 percent) had local progression of their prostate cancer over time.
- 41/223 men (18.4 percent) had progression to evident metastatic disease over time.
- 38/223 men (17.0 percent) died of prostate cancer.
- Prostate cancer-specific survival decreased between 15 and 20 years of follow-up but then stabilized again after 20 years.
- 9/223 men were initially diagnosed with a Gleason score of 8 to 10.
- All 9 of these men (100 percent) died within 10 years of follow-up.
- 5/9 of these men (55.5 percent) died of prostate cancer.
- Among men with well-differentiated, non-palpable tumors at diagnosis,
- Overall survival declined slowly for the first 20 years.
- Overall survival declined more rapidly between 20 and 25 years of follow-up.
As we might have expected, the authors conclude that:
Although localized [prostate cancer] most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.
They are also careful to note that it is hard to know how to take practical advantage of these data and apply them in the PSA era (although we do know that PSA testing clearly adds some 7-10 years of “lead time” to the time at which a man with localized disease might be diagnosed based on clinical criteria alone).
So here are a number of other potential take-aways from this study:
- Men initially diagnosed today with Gleason 8-10, localized disease (only 4 percent of the above series) clearly need immediate treatment unless they have a very limited life expectancy for other reasons.
- Men initially diagnosed today with D’Amico, low-risk prostate cancer have a high probability of 15 to 20 years of prostate cancer-specific survival even if some form of monitoring is the only initial form of management.
- Men who are initially observed but progress to metastatic disease (18.4 percent of the patients in this study) have a high probability of prostate cancer-specific mortality (55.5 percent in this study).
Until we have comparable data from a 30-year series of men rigorously monitored on an active surveillance regimen (i.e., at least 20 years from now), it will be impossible to offer any really accurate comparison between the men in this study (all diagnosed in the early 1980s and therefore in the pre-PSA era) and the men diagnosed by researchers like Klotz (in Canada) and Carter (at Johns Hopkins) and managed by careful monitoring of their PSA levels and repeat biopsies.
However, what this study does show us, once again, is that:
- Yes, there is a long-term risk of disease-specific mortality associated with simple monitoring of localized prostate cancer.
- That risk is relatively small for men with localized disease and Gleason scores of 7 or less.
Note that even in the above study, only 33/214 men (15.4 percent) died of prostate cancer within a 30-year follow-up period. We have not seen the full text of this paper, but if most of these men had any other indicator for D’Amico high-risk disease (e.g., a PSA level > 20 ng/ml or a clinical stage of T2b or higher at diagnosis), then it becomes arguable that the natural history of prostate cancer in the PSA era may show that almost no patients initially diagnosed with low- or intermediate-risk disease are at significant risk for prostate cancer-specific mortality within 30 years of follow-up.
Having said this, The “New” Prostate Cancer InfoLink wishes to be very clear indeed that avoiding death from prostate cancer is not the only possible reason why it might be wise to have treatment for early stage, localized disease. Avoiding the potential future symptoms of progressive and/or metastatic disease are also viable reasons for early treatment, … but only if one has a full appreciation of the risk/benefit equation on which one’s decisions are being based.