Today’s news items all focus on issues that are closely connected to the recent and controversial guidelines issued by the US Preventive Services Task Force:
- The accuracy of current methods for predicting the likelihood of clinically insignificant (indolent) prostate cancer
- The management of patients found to have incidental prostate cancer on treatment for benign prostatic hyperplasia (BPH), and
- The risks of overtreatment of men in their 70s and 80s after a diagnosis of prostate cancer
Chun et al. have just published data suggesting that, despite a high accuracy, currently available models for prediction of “insignificant” prostate cancer are incorrect in 10 to 20 percent of cases. They also state that the rate of misclassification is further inflated when specific cutoffs are used. They conclude that, “extreme caution is advised when statistical tools are used to assign the diagnosis of” insignificant prostate cancer. Chun and colleagues set out test the ability to identify insignificant prostate cancer prior to definitive therapy. Based on a cohort of 1,132 men, they developed a nomogram to predict the probability of insignificant prostate cancer. Predictors consisted of prostate-specific antigen (PSA), clinical stage, biopsy Gleason sum, core cancer length, and percentage of positive biopsy cores (percent positive cores). They defined insignificant prostate cancer as organ-confined disease (OC) with tumor volume < 0.5 cm3 and without Gleason 4 or 5 patterns. Finally, an external validation of the most accurate current nomogram for prediction of indolent prostate cancer (the Kattan nomogram) was performed in the same group. Insignificant prostate cancer was pathologically confirmed in 65/1,132 men (5.7 percent). The predictive accuracy of the new nomogram was 90 percent as compared to 81 percent for the older nomogram. However, in cutoff-based analyses of patients who were qualified by our and the older nomograms as being at high probability for insignificant prostate cancer, 63 percent and 45 percent respectively harbored aggressive prostate cancer variants at radical prostatectomy (Gleason score 7-10, extracapsular extension, seminal vesicle invasion, and/or lymph node invasion). Editorial comment on this article is also provided by Evans on the UroToday web site.
There is continuing controversy about the appropriate management for patients with incidental prostate cancer after surgery for benign prostatic hyperplasia (BPH). Capitanio et al. have tested the accuracy of preoperative clinical variables in predicting residual disease and biochemical recurrence in patients with incidental prostate cancer treated with radical retropubic prostatectomy RRP). They analyzed data from 126 patinets with T1a-T1b prostate cancers diagnosed at surgery for BPH between 1995 and 2007. All patients underwent RRP within 6 months of surgery for BPH. Seventy-five patients (59.5 percent) were stage T1a and 51 (40.5 percent) were stage T1b. At RRP, 21 patients (16.7 percent) were pT0 and 7 patients (5.6 percent) had extraprostatic disease (pT3). PSA levels before and after surgery for BPH and Gleason score at surgery for BPH were the only independent predictors of residual cancer at RRP. Neither disease stage (T1a vs T1b) nor the rate of biochemical recurrence predicted residual cancer. With a mean follow-up of 57 months, the 5- and 10-year biochemical recurrence-free survival rates were 92 and 87 percent, respectively. PSA after surgery for BPH and Gleason score at surgery for BPH were the only significant multivariate predictors of biochemical recurrence. The authors conclude that PSA levels measured before and after surgery for BPH and Gleason score at surgery for BPH were the only significant predictors of the presence of residual cancer at RRP. PSA level measured after surgery for BPH and Gleason score at surgery for BPH were the only independent predictors of biochemical recurrence after RRP.
Finally, Jeldres et al. have used the Quebec Health Plan database to examined the rate of 10-year survival in 70- and 80-year-old men treated for prostate cancer with either attempted curative external beam radiotherapy (EBRT) or radical prostatectomy (RP). They stared from the hypothesis that the life expectancy of candidates for attempted curative therapy of prostate cancer should not be less than 10 years. Within the Quebec Health Plan cohort of 17,570 EBRT or RP patients, 6,183 men aged 70 years or older were treated with either RP (n = 1,591) or EBRT (n = 4,592) and represented the focus of crude survival analyses. The database contained no information on tumor stage or grade, PSA levels, or cause-specific mortality. The researchers controlled for the potential effect of prostate cancer-specific mortality by performing an analysis in a subset of 2,704 men (RP, n = 881; EBRT, n = 1,823) who had no clinical evidence of disease relapse of prostate cancer. Overall actuarial 10-year survival was 38.5% percent (RP 59.3 vs. EBRT 30.3 percent, p < 0.001) versus 36.5 percent in those without clinical evidence of disease relapse (RP 63.8 vs. EBRT 22.6 percent, p < 0.001). In multivariate Cox regression models, EBRT was associated with a 2.1-fold (p < 0.001) and 2.9-fold (p < 0.001) higher risk of mortality relative to RP in all men and in men without clinical evidence of disease relapse, respectively. The authors conclude that 40 percent of septa- and octogenarian men who are selected for RP do not have adequate life expectancy to warrant attempted curative therapy. Even more strikingly, 70 percent of men who receive EBRT die before reaching the 10-year mark. These data are sugggestive of the idea that more selective criteria are needed to prevent elderly men from the harms of treatment if treatment is, in fact, unlikely to be of real benefit. The Iowa Prostate Cancer Consensus would appear to suggest a model for limiting the risk of overtreatment of elderly patients.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Treatment | Tagged: BPH, cancer, elderly, indolent, insignificant, Kattan, life expectancy, mortality, news, nomogram, patients, prediction, prostate, prostatectomy, radical, survival, update |