[Editorial comment: The “New” Prostate Cancer InfoLink thanks the late Ralph Valle for his permission to use significant portions of the content of the following article, which is based on his research.]
Conservative treatment of prostate cancer has a long natural history. This history was written years before the advent of the PSA era, and the best documented details of that history exist in the data compiled by the Scandinavian cancer registries and the studies of those data.
What do we mean by conservative treatment? To all intents and purposes, conservative treatment of prostate cancer meant that men were not being “screened” for any risk of prostate cancer and so nothing was being done until a man showed clear symptoms of prostate cancer. If a man had no symptoms, nothing was done. When a man showed symptoms (urinary retention, bone pain, etc.), these symptoms would be treated (“palliated”) so that the patient would have the best possible quality of life, but treatment was not carried out with curative intent.
For the most part, between 1970 and 1990, this is how prostate cancer was treated in Scandinavia, where excellent long-term health records are available going back decades. By looking at what happened to these men with conservatively treated prostate cancer, we can understand how the disease progresses when it is effectively undisturbed (untreated) until late in its course.
So let’s look at the available data, complied over the years in seven major Scandinavian analyses:
In 1994, Grönberg et al. reported that patient age alone can be a significant prognostic factor in prostate cancer. They analyzed data from a large and unselected cohort of 6,890 prostate cancer patients diagnosed between 1971 and 1987 in northern Sweden. Tumor grade information showed that 26.4 percent of the patients had well-differentiated tumors (grade 1), 40.0 percent had moderately differentiated tumors (grade 2), and 17.7 percent had poorly differentiated tumors (grade 3). There were no data to suggest that tumors in younger patients are more aggressive per se. However, loss of life expectancy differed significantly among all age classes and in all three grades. In patients with grade 1 tumors the time lost due to prostate cancer ranged from 11.0 years in the youngest age group to 1.2 years in oldest age stratum, even though the relative survival was approximately 0.70 in all age classes.
In 1996, Adolfsson published data on 172 Swedish patients diagnosed with T1-3NxM0 prostate cancer. These patients were all diagnosed between 1978 and 1982 and followed for at least 10 years using a surveillance protocol with deferred treatment on symptomatic progression. The median age at diagnosis was 68 years. The disease-specific survival at 10 years was 80 percent for the total series, 84 percent for the subgroup with T1-2 tumors, and 92 percent for patients with T1-2 tumors diagnosed when the patients were less than 70 years of age. For the subgroup with T3 tumors, the disease-specific survival at 9 years was 70 percent. In all subgroups the competing mortality was higher than the prostate cancer mortality.
In 1997, Johansson et al. published the results of a population-based study of 642 patients in Orebro, Sweden, with prostate cancer of any stage. The patients were consecutively diagnosed between 1977 and 1984, had an average age of 72 years, and were followed until 1994. Prostate cancer accounted for 201 of all 541 deaths (37 percent). Among 300 patients initially diagnosed with localized disease (T0-2), 33 (11 percent) died of prostate cancer. The corrected 15-year survival rate of 81 percent among these 300 patients was similar in 223 patients who had deferred treatment and in 77 who received initial treatment. The corrected 15-year survival was 57 percent in 183 patients initially diagnosed with locally advanced cancer (T3-4) and 6 percent in the 159 patients who had distant metastases at the time of diagnosis.
Also in 1997, Grönberg et al. published data from a study population of 6,514 patients diagnosed with prostate cancer between 1971 and 1987 in northern Sweden. About 85 percent of these patients died during the follow-up period, and the prostate cancer-specific mortality was estimated to be 55 percent. Age at diagnosis was found to be a strong predictor of prostate cancer death. Patients diagnosed before the age of 60 had an 80 percent risk of dying of prostate cancer, whereas those over 80 years of age at diagnosis had less than a 50 percent risk of prostate cancer-related death.
In 1999, Adolfsson et al. published a report on a prospective study of long-term survival in 50 selected men with locally advanced, non-metastatic prostate cancer managed with deferred treatment. The men were treated if and when symptoms occurred or upon their request. All patients were followed until December 1994, and no patient was lost to follow-up. The median patient age at diagnosis was 71 years. All patients were followed for at least 144 months or died before then. Actual overall survival rates at 5, 10, and 12 years were 68, 34, and 26 percent; disease-specific survival rates were 90, 74, and 70 percent, respectively. A third of the patients had received no cancer-specific treatment at follow-up or before death.
In 2004, Johansson et al. published additional data on the 223 men from the original Orebro study (see above) who had received deferred treatment. By this time, this patient cohort had then been followed for an average observation period of 21 years. The patients who had had tumor progression were treated hormonally (either by orchiectomy or with estrogens) if they had symptoms. After complete follow-up, 39/223 patients (17 percent) experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. However, further follow-up from 15 years (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0 to 36.0 percent), survival without metastases (from 76.9 to 51.2 percent), and prostate cancer-specific survival (from 78.7 to 54.4 percent). The prostate cancer mortality rate increased from 15 per 1,000 person-years during the first 15 years to 44 per 1,000 person-years beyond 15 years of follow-up.
Last, but by no means least, in 2009 Andrèn et al. used a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden to show that 26.6 percent of men diagnosed with and affected by prostate cancer died of their disease.
While there is considerable variation in the results of these seven studies, several things seem to be very clear:
- Early stage, low and intermediate grade disease can be treated successfully with conservative therapy in older men with at least 10 and perhaps 15 years of life expectancy.
- More aggressive prostate cancer results in a high rate of mortality when left untreated.
- Age is an important factor in decision making.
- If early disease is diagnosed at a young age, there is a high risk of the patient dying from prostate cancer if treated conservatively.
In the USA, only the Connecticut Tumor Registry appears to offer data sufficiently comprehensive over a long enough time period to carry out studies similar to those published from the Scandinavian databases.
Albertsen et al. initially reported an analysis of data from the Connecticut registry in 1998. The study was designed to estimate survival based on a competing risk analysis stratified by age at diagnosis and histologic findings for men diagnosed as having clinically localized prostate cancer and who were managed conservatively. It included a total of 767 unscreened men with localized prostate cancer diagnosed between 1971 and 1984, aged 55 to 74 years at diagnosis, either not treated or treated with immediate or delayed hormonal therapy, and followed up for 10 to 20 years after diagnosis. This study had a dramatic impact on the understanding of risk of death from prostate cancer in the USA and its association with Gleason score. Albertsen et al. showed that men with tumors that had Gleason scores of 2-4, 5, 6, 7, and 8-10 faced a 4-7, 6-11, 18-30, 42-70, and 60-87 percent chance, respectively, of dying from prostate cancer within 15 years of diagnosis, depending on their age at diagnosis.
Valle reports asking for guidance from Dr. Albertsen on what to tell a 55-year-old man diagnosed with prostate cancer in 1999 with respect to conservative management. Albertsen responded as follows:
Concerning your 55 year old man, I would recommend the following. If he has high-grade disease, our study indicates that he has a high probability of dying from prostate cancer if he elects conservative treatment. Therefore I would encourage him to do something. For men with low-grade disease, this is a difficult problem. I would probably still recommend more aggressive treatment because of the long life expectancy, but if the patient wanted to wait because of potency concerns or something else, our study tries to estimate his probability of progression over a period of 15 years.
(P. Albertsen, personal communication with R. Valle, 1999).
When Albertsen and his colleagues reassessed these data in a publication in 2005, they showed that there had been no significant change in the risk for prostate cancer-specific mortality.
Finally, in a paper published in 2007, Albertsen et al. reported the results of a retrospective, population-based study to estimate prostate cancer-specific survival and overall survival after surgery, radiation or observation to manage clinically localized prostate cancer. Again using the Connecticut Tumor Registry database, they identified Connecticut residents aged 75 years or younger and diagnosed with clinically localized prostate cancer between January 1, 1990 and December 31, 1992. They obtained information from physician offices concerning treatments received by 1,618 patients who underwent surgery (802), external beam radiation therapy (702), or no initial therapy (114) and the subsequent medical outcomes. Treatment comparisons were adjusted for pretreatment Gleason score, PSA level, and clinical stage as well as age at diagnosis and comorbidities. At an average follow-up of 13.3 years, 13 percent of patients had died of prostate cancer, 5 percent had died of other cancers, and 24 percent had died other causes. Patients undergoing surgery were younger, and had more favorable histology and lower pretreatment PSA levels compared to patients undergoing radiation. Patients who elected observation had significantly worse cause-specific survival than those who elected surgery. They also fared worse than men who received radiation therapy but the difference was not statistically significant, possibly because of the small number of prostate cancer-specific deaths to date.
Patients who are interested in the possibility of treatment using conservative forms of management are also advised to read the sections on Active surveillance and watchful waiting and on The downsides of conservative management.
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