We previously reported a sharp rise in the proportion of prostate tumors diagnosed with low-risk features during the CaPSURE project up to 2001.9
This trend has not continued during this decade to date; the distribution of tumors has remained relatively constant across the three risk strata since the prior analysis. On the other hand, within the low-risk group, there are significant, ongoing trends toward lower-risk characteristics. Nonpalpable, T1c tumors account for an ever-growing proportion of low-risk tumors, up to 78% from 30% across the study period. T1c tumors are associated with lower risk of recurrence than T2a tumors under the Kattan nomogram12
but not under the CAPRA scoring system.10
T1a/b tumors detected by transurethral resection for presumed benign disease account for a negligible proportion of contemporary tumors.
Biopsy specimens assigned a Gleason score below 6 likewise account for only 3% of low-risk tumors in 2004-2006, consistent with a well-documented change in pathologists' practices.15
Of note, however, a few tumors were assigned a primary or secondary Gleason pattern of 2 even in 2006. The mean PSA value among low-risk tumors continues to decrease, with tumors increasingly likely to be diagnosed with PSA values of 2 to 6 ng/mL rather than 6 to 10 ng/mL. Those diagnosed with a PSA value <2 ng/mL represent a relatively constant fraction. A total of 68.8% of these were palpable T2a tumors diagnosed by abnormal digital rectal examination results and 9.9% were T1a/b. The remaining 21.3% were T1c; it is unclear what prompted the biopsy among these patients—perhaps a strong family history, rapid PSA velocity, or abnormal digital rectal examination results on the contralateral side from the positive biopsy specimen, coded by the diagnosing urologist as T1c.
The trends in stage and Gleason grade represent continuation of trends we previously reported,9
whereas the prior study did not document a decline in PSA levels between 1993 and 2001, perhaps due to different categorization of PSA values (0-4 vs 4-10 ng/mL); the mean PSA value was not assessed in the earlier study. The present analysis is the first to our knowledge to examine time trends in PPB rates. The mean PPB decreased by nearly 50% during the 1990s and has stabilized since the beginning of the new decade. However, there is an ongoing increase in the proportion of tumors diagnosed with ≤10% of positive biopsy cores—i.e., a single core of at least a 10-core biopsy. These now represent more than one third of low-risk tumors, reflecting increased use of extended-template biopsy techniques.16
Multivariable risk analyses yield further insights. The low-risk group has been described as facing an 85% likelihood of biochemical recurrence-free survival after RP.6
The preoperative Kattan predicted likelihood of 5-year recurrence-free survival for this group varied from 70% to 96%; in this series the mean Kattan predictions were essentially constant at approximately 90%. Mean CAPRA scores, on other hand, decreased from 2.0 to 1.4, with tumors with CAPRA scores of 0 to 1—representing the lowest risk patients—increasing from 26% to 60% of low-risk tumors. We found that the CAPRA score was able to substratify RP patients well within the low-risk group; with increasing CAPRA score, the hazard ratios for recurrence progressed upward, and 5-year actuarial survival declined consistently.
A typical low-risk patient could be assigned a CAPRA score up to 3 for age older than 50 years, PSA value of 6 to 10 ng/mL, and/or a PPB of >33%. A few patients in the low-risk group had CAPRA scores of 4 to 6 because the traditional low-risk group is defined by total Gleason score and thus includes rare patients with Gleason 2+4 or 4+2 biopsy specimens. The survival results in this analysis for patients with CAPRA scores of 4 to 6 should not be taken as typical for all RP patients with these scores, but illustrate the point that the presence of Gleason pattern 4 disease drives outcomes, and Gleason 2+4 or 4+2 tumors should not be included with low-risk patients in outcomes analyses.
With regard to treatment trends among low-risk patients, we previously reported a sharp decline in use of active surveillance, from 20.3% in 1993-1995 to 7.9% in 1999-2001, and raised the concern regarding possible overtreatment among low-risk patients.9
A recent analysis from the population-based Surveillance, Epidemiology, and End Results (SEER) registries reached similar conclusions regarding underutilization of surveillance among low-risk patients, estimating overtreatment rates of 10% of RP and 45% of radiation therapy patients whose cancer was diagnosed in 2000-2002. Two important limitations of this study are that it considered “lower-risk” patients to be those with Gleason scores of 2 to 4 or those older than 70 years with Gleason scores of 5 to 7, an outdated classification of Gleason grading, and that it included primary ADT with “expectant management,” which may not be valid in terms of cost, quality-of-life, or outcomes.17
With increasing appreciation of the role of active surveillance for selected patients with low-risk tumors, we now find a reversal of the trend, with active surveillance rising from 6.2% of patients in 2000-2001 to 10.2% in 2005-2006. Use of brachytherapy has fallen from a peak of 19.4% in 2000-2001 to 13.0% in 2005-2006, whereas use of RP has risen to nearly 60% of low-risk patients. Use of both primary ADT and NADT has decreased from peaks, respectively, of 10.6% and 15.2% in 2000-2001 to 6.6% and 11.6%, also marking a reversal of trends previously documented in both CaPSURE and SEER.9, 18
This study has limitations. Data are submitted only by patients and urologists; therefore, any treatments by other practitioners that are not reported by patients either to their urologists or in their questionnaires may be missed. Quality assurance mechanisms, including medical record review of all hospital admissions, help to minimize this problem. An enrollment bias may persist which could artificially lower the proportion of observation patients: patients who are diagnosed as having prostate cancer but who elect not to undergo treatment may simply monitor their PSA levels with their primary care provider, or not at all. If diagnosed as having prostate cancer by a CaPSURE urologist and enrolled in the database, however, patients should have completed at least one treatment questionnaire.
The CaPSURE practice sites have not been chosen at random and thus do not constitute a statistically valid sample of the United States patient population. However, they represent a broad range of geographic locales and a mix of academic and community sites, which we believe to be the best available sample for the analysis of temporal trends in “real-world” practice. It is possible that the results would have been different with different grouping of the years of diagnosis, but given the consistently strong trends and low p-values realized, this seems unlikely. The 1998 Kattan preoperative nomogram has recently been updated by Stephenson et al,19
and the 2006 version incorporates more detailed information on biopsy cores taken and positive. It is quite possible that the 2006 nomogram would better reflect a decline in risk within the low-risk group, and would be more relevant to contemporary patients. However, the newer nomogram has not yet been validated in the community setting, and cannot readily be calculated for large numbers of patients. The CAPRA score has to date been validated only for RP patients, and results of our survival analysis should not yet be extrapolated to patients undergoing other treatments.