THE "NEW" PROSTATE CANCER INFOLINK

Additional prostate cancer news this weekend includes the following items:

• The role of follow-up pathology in patients with clinical stage T1a (TURP-detected) prostate cancer
• The impact of the number of risk factors on the likelihood of prostate cancer-specific mortality in patients with intermediate- and high-risk disease
• Whether a familial history of prostate cancer affects outcomes following brachytherapy for localized disease
• Whether obese men are at greater risk for delayed diagnosis of prostate cancer and subsequent poorer outcomes based on current PSA screening recommendations

When minimal prostate cancer (clinical stage T1a) is detected in tissue sampled after a transurethral resection of the prostate (TURP), it is uncertain how extensively the remaining tissue should be sampled for accurate grading and staging. Trpkov et al. prospectively and randomly examined all TURP samples sent to their institution for 1 year. When minimal cancer was found, they performed additional partial sampling, followed by complete submission of all remaining tissue. All samples were evaluated separately to identify possible changes in Gleason score and tumor volume. They also performed a careful cost analysis for the additional tissue sampling. Of the 747 TURP samples evaluated, 125 (16.7 percent) contained prostate cancer. Minimal cancer involving less than 5 percent of sampled tissue was found in the initial submission in 26 patients (3.5 percent). Initial Gleason scores and tumor volumes were not changed in any of the studied cases after evaluating the additional partial and complete samples. The authors calculated a cost of Can$4,336 per year for the additional sampling of TURPs with minimal cancer. They conclude that when minimal cancer was found in the initial TURP samples, additional partial and complete sampling did not change the initial Gleason scores or tumor volumes.

Nguyen et al. studied data from 1,063 men who underwent radical prostatectomy (n = 559), external beam radiotherapy (n = 288), or radiotherapy plus androgen suppression therapy (n = 116) for prostate cancer between 1995 and 2002. Their objective was to determine whether a patient’s number of unfavorable risk factors could be used to predict his risk of prostate cancer-specific mortality (PCSM) among men with intermediate- to high-risk prostate cancer. Specifically, they determined whether an increasing number of unfavorable risk factors (prostate-specific antigen level >10 ng/mL, Gleason score ≥ 7, clinical stage T2b or greater, or pretreatment PSA velocity > 2.0 ng/mL/y) was associated with the interval to PCSM and all-cause mortality. Median follow-up was 5.6 years. Compared with the PCSM for patients with just one risk factor, the adjusted hazard ratio was 2.3 for two risk factors, 5.4 for three risk factors, and 13.6 for all four risk factors. The 5-year cumulative incidence of PCSM was 2.4 percent for one and for two factors, 7.0 percent for three factors, and 14.7 percent for all four factors. Prostate cancer deaths as a proportion of all deaths were 19, 33, 53, and 84 percent for one, two, three, and all four factors, respectively. Nguyen and his colleagues conclude that the number of unfavorable risk factors was significantly associated with PCSM and that prostate cancer was the major cause of death in men with at least three risk factors. They recommend that these men should be considered for clinical trials designed to assess whether survival is prolonged with the addition of novel agents to current standards of practice. [Please note that the published abstract states that the data on which this study are based were collected between 1965 and 2002. We have checked with the authors; there was a typographic error. The correct dates are in fact 1995 and 2002, as stated above.]

Peters et al. have published what is believed to be the first assessment of the impact of hereditary prostate cancer on the prognosis of patients treated with brachytherapy with or without external beam radiotherapy (EBRT) and/or androgen deprivation therapy for clinically localized prostate cancer. A total of 187 of 1,738 consecutive patients with localized prostate cancer (cT1-3, N0/X, M0) had a family history of prostate cancer in a first-degree relative and received low-dose-rate brachytherapy alone or in combination with EBRT or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months. For low-risk patients, both groups (i.e., patients with and without a first-degree relative) had similar actuarial 5-year FFBF (97.2 vs. 95.5 percent). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-year FFBF 100 vs. 93.6 percent). For the high-risk patients, men with a positive family history had a similar 5-year FFBF (92.8 vs. 85.2 percent). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. The authors conclude that men with a positive family history have clinical and pathologic characteristics and biochemical outcomes similar to those with no familial history of the disease.

Freedland et al. hypothesized that PSA-based screening is biased against obese men due to dilution of PSA in the bloodstream, and thus results in delayed diagnoses and poorer outcomes beyond the biological link between obesity and aggressive prostate cancer. They therefore investigated the association between body mass index (BMI) and the outcome of radical prostatectomy (RP) separately for men with PSA-detected cancers (cT1c) or with abnormal digital rectal examination (DRE) findings (cT2/T3), and stratified by year of treatment, using two large databases including a total of 3,389 patients treated by RP between 1988 and 2007. Data were examined as a whole and as stratified by clinical stage (cT1c vs cT2/T3) and year of surgery (after January 1, 2000 vs before January 1, 2000). In both cohorts a higher BMI was associated with high-grade disease and more positive surgical margins; these results did not vary by clinical stage. Furthermore, a higher BMI was significantly associated with biochemical progression in both cohorts. When stratified by clinical stage, obesity was significantly related to progression in both cohorts among men with T1c cancers  but not in men with cT2/T3 cancers. Among men with T1c disease, the association between BMI and biochemical progression was limited to men treated on or after January 1, 2000, and was not apparent in men treated before January 1, 2000. The authors conclude that obese men in these two databases with PSA-detected cancers and treated with RP since 2000 were at significantly greater risk of biochemical progression, while obese men treated before 2000 or diagnosed with an abnormal DRE were not at significantly greater risk of progression. These findings support the hypothesis that current PSA-based screening is less effective at finding cancers in obese men, leading to more aggressive tumours at diagnosis. Lowering the PSA threshold for biopsy among obese men might help to improve outcomes among this high-risk group.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Treatment | Tagged: BMI, brachytherapy, cancer, factors, familyt, Gleason, hereditary, history, mortality, news update, obesity, outcome, prostate, prostatectomy, PSA, radical, risk, stage, T1a, TURP, velocity |