The staging systems used by clinicians and pathologists for assignment of the stage of prostate cancer were all developed more than 20 years ago, and have seen only relatively minor adjustments since the introduction of the PSA test.
In a paper published in the Journal of Urology in June, Reese et al. called into question the significant of the differences between the clinical T1 and T2 stages in patients being diagnosed today, and their relevance to decisions about initial treatment. They have expanded on this issue in a recent submission to Beyond the Abstract on the UroToday web site.
In their original paper, Reese et al. reported on an analysis of data from men registered in the CaPSURE database. Eligible men had to have been diagnosed with localized prostate cancer (clinical stage T1 or T2) and treated by radical prostatectomy. The authors then set out to investigate the relative usefulness of clinical stage compared to other clinical parameters in the prediction of their pathological outcomes and risk for biochemical recurrence.
The results of their study showed the following:
- The study cohort comprised 4,899 patients.
- 51.9 percent (2,543/4,899) were classified as having clinical stage T1 disease at diagnosis.
- 48.1 percent (2,356/4,899) were classified as having clinical stage T2 disease.
- On univariate analysis, clinical stages T2b and T2c were associated with pathological outcomes but only clinical stage T2b was associated with biochemical recurrence.
- Also on univariate analysis, PSA level, biopsy Gleason score, and percent of positive biopsy cores were strongly associated with recurrence and adverse pathological outcomes.
- On multivariable analysis, clinical stage was of no apparent value in determining pathological or biochemical outcomes.
We know that there has been a major “stage shift” over the past 20 years, and that — in general — today’s prostate cancer patient is being diagnosed much earlier and at lower clinical stage than was true in the past.
In their Beyond the Abstract commentary, Reese and Cooperburg attempt to offer an explanation of what may really be driving the decreasing relevance of clinical staging to prognosis in men diagnosed with localized prostate cancer today. They make the following points:
- Widespread PSA screening means that most cancers are diagnosed before they become palpable on rectal examination. Thus, a suspicious DRE today is more likely to reflect benign findings which are incidental to the cancer than actual cancer. However, such patients would be staged as cT2, even though their clinical behaviors would be more like those of patients with T1c disease.
- A palpable nodule on DRE, or a visible lesion on transrectal ultrasound, is typically thought to indicate a larger volume tumor, but the percentage of positive biopsy cores is a more reproducible and likely more accurate measure of tumor volume than DRE or ultrasound. The inclusion of percentage of positive biopsy cores into modern predictive models (such as the Kattan nomograms) may have rendered clinical staging data irrelevant for patients with localized disease.
- Another (as yet unpublished) analysis of data from the CaPSURE database suggests that there is widespread variation in the interpretation and application of clinical staging guidelines, resulting in the incorrect clinical stage being assigned to a high percentage of patients with prostate cancer. This could also diminish the predictive power of clinical stage.
- Even after correcting for staging errors in this unpublished data set, there was no association between advanced clinical stage and biochemical recurrence rates after radical prostatectomy.
Now it is interesting to look at the findings of Reese et al. in association with a newly published article on the impact of PSA screening on the incidence of prostate cancer in Sweden between 1999 and 2007. (The Swedish National Prostate Cancer Registry includes data on approximately 95 percent of all Swedish prostate cancer cases.)
According to Bratt et al., about a third of all men in Sweden between 50 and 75 years of age received at least one PSA test between 2000 and 2007, even though widespread PSA screening is not recommended. In their study Bratt et al. were also able to show the following:
- The age-standardized annual incidence of prostate cancer in Sweden was
- 187/100,000 men in 1999
- 233/100,000 men in 2004
- 196/100,000 men in 2007
- The incidence of asymptomatic cases (regardless of their DRE result) also peaked in 2004 (at 62/100 000 men), although there was considerable regional variation.
- Between the years 2000 and 2007, the proportion of newly diagnosed, asymptomatic cases rose from 15 percent of all new cases to 30 percent.
- Patients with either asymptomatic disease or symptomatic disease that was still clinical stage T1c constituted 29 percent of all new cases in 2000 and 52 percent of all new cases in 2007.
(In understanding the above data, it is important to remember that all patients with a negative DRE are, by definition, clinical stage T1c. It is possible to have symptoms of a urinary tract problem but still to have a DRE that is negative for signs of prostate cancer, which means that symptomatic patients can indeed be appropriately classified as clinical stage T1c.)
The combination of the data from these two papers really do start to make one wonder just how relevant the current clinical staging criteria are for patients diagnosed with localized prostate cancer today. Reese and Cooperberg suggest that — for starters — clinical stage data should not be emphasized when predicting patient outcome after radical prostatectomy, nor in risk-stratifying patients for research studies. It is important to bear in mind, however, that pathological staging may still have high relevance to projection of outcomes after a radical prostatectomy.
Filed under: Diagnosis, Management, Risk Tagged: | clinical stage, Diagnosis, prognosis, relevance, staging
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Thanks for reporting this issue and the papers.
Here are a couple of thoughts about this.
First, when you look at the Partin tables (2001 version for me), a difference between stage 1 and stage 2 (and whether a, b, or c) does make quite a difference in whether the disease is organ-confined as well as among the other variables displayed. How can we square the CaPSURE interpretation with the Partin tables? One difference is that the 2001 Partin tables were probably based predominantly on expert and consistent staging at Johns Hopkins. Perhaps the lack of consistent staging in the CaPSURE data explains low salience of stage in the univariate and multivariate analyses. (My own challenging case was staged at T2 at one well-known institution and at T3 at Johns Hopkins — following what I’ll call a most diligent DRE).
The second is that the authors do not address PSA velocity, which now appears quite important for patients diagnosed with prostate cancer, per the results from the D’Amico teams, as confirmed by others, regarding a rise of more than 2.0 in the year prior to diagnosis. It’s likely the CaPSURE database did not have such data, but there’s strong evidence that PSAV should be a standard part of staging, where possible.
The Partin tables and the Kattan nomograms (and the D’Amico criteria) are all based on databases constructed from data collected at academic cancer centers. By contrast, the CaPSURE database is a community urology database.
This does not make one “right” and the other “wrong.” It merely represents the differing priorities and drivers of the patients and the clinicians at the different institutions.
The critical question, it seems to me, is whether it does or should make any difference to treatment recommendations for an individual patient today if a man is staged clinically as T1 or T2 when all other factors are equal.
If a patient has been mis-staged as T2 when he is actually T3, that is a whole other issue — as is the relevance of PSA velocity.