THE "NEW" PROSTATE CANCER INFOLINK

Today’s news items are focused on issues affecting risk for prostate cancer and risk for progression after treatment, and the ways these risks can be affected by available data:

• Does the regular use of NSAIDs affect risk for prostate cancer, or just affect PSA levels?
• Do prostate size and intensity of biopsy sampling impact risk for Gleason sum upgrading post-surgery?
• Are there other specific factors that affect risk for Gleason sum upgrading (or downgrading) post-surgery?
• How do other factors discovered at the time of surgery that affect risk for biochemical progression?

It has long been known that inflammation may have an association with the development of prostate cancer; therefore, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can potentially decrease the risk of prostate cancer. However, no precise correlation between oral NSAID use, serum PSA levels, and prostate cancer risk has ever been established. In this study, Singer et al. evaluated serum PSA levels together with NSAID and acetaminophen consumption in 1,319 men aged > 40 years in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). The results show that NSAID and acetaminophen consumption display a negative association with PSA levels. In other words, individuals who reported using NSAIDs (19.8 percent of participants) or acetaminophen (1.3 percent) regularly had lower PSA levels than individuals who did not take these drugs. PSA levels among NSAID users were 0.9 times the levels among nondrug takers (P = 0.038), whereas PSA levels among acetaminophen users were 0.76 times the levels in nondrug takers (P = 0.14).  Individuals who stated they took both NSAIDs and acetaminophen (about 1 percent of study participants) on a regular basis had higher PSA levels (1.8 times greater; P = 0.24) than individuals who stated they did not take either of these drugs regularly. The authors conclude that regular NSAID consumption may reduce serum PSA levels. Whether this is indicative of a protective effect on prostate cancer risk or masks possible prostate injury resulting in reduced detection of prostate cancer is unclear. Given the widespread consumption of NSAIDs in the US, and the regular use of PSA for the assessment of prostate cancer risk, the potential implications of the findings may be substantial.

Turley et al. have published an intellectually interesting paper in which they test the hypothesis that the association between prostate size and risk of Gleason grade upgrading varies as a function of sampling. They conducted a retrospective analysis of the association between pathological prostate weight, prostate biopsy scheme, and Gleason upgrading (Gleason sum ≥7 at radical prostatectomy, RP) among 646 men with biopsy Gleason sum  2-6 disease treated with RP between 1995 and 2007 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. The database included 204 men who had a sextant (six or seven cores) biopsy and 442 men who had an extended-core biopsy (eight or more cores). Analyses were adjusted for center, age, surgery, preoperative PSA level, clinical stage, body mass index, race, and percentage of cores positive for cancer. A total of 281 men (44 percent) were upgraded after surgery; a smaller prostate was positively associated with the risk of upgrading in men who had an extended-core biopsy (P < 0.001), but not among men who had a sextant biopsy (P = 0.22). The interaction between biopsy scheme and prostate size was significant (P interaction = 0.01). The authors conclude that the data support the hypothesis that the risk of upgrading is a function of two opposing contributions: (i) the presence of a more aggressive type of cancer (a more aggressive phenotype) in smaller prostates and thus an increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus a decreased risk of upgrading. They go on to propose that when prostates are sampled more thoroughly, the phenotype association dominates and smaller prostates are therefore linked with an increased risk of upgrading. In less thoroughly sampled prostates, however, they suggest that the opposing factors cancel each other out, resulting in no association between prostate size and risk of upgrading. The authors believe that their findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading.

Moussa et al. have investigated the clinical and pathological variables that predict pathological changes in men with prostate cancer who have an intermediate- or high-grade biopsy Gleason score (GS) of ≥ 7 and who are upgraded or downgraded post-surgery on interpretation of radical prostatectomy (RP)  specimens. They retrospectively evaluated data from 1,129 patients who had RP after a biopsy showing a GS of ≥ 7 between 2000 and 2007. The overall mean age of the patients was 61 years, with a median PSA level of 6 ng/ml. Of the 1,129 patients, the surgical GS was upgraded in 296 (26.2 percent), downgraded in 210 (18.6 percent), and remained the same in 623 (55.2 percent). Factors predicting a surgical GS upgrade were a higher PSA level (P = 0.005), presence of perineural invasion (P = 0.043), absence of inflammation (P < 0.001), and absence of associated high-grade prostatic intraepithelial neoplasia (P = 0.02). The number of positive biopsy cores (P = 0.033) was a predictor of upgrading. Large prostate volume (P = 0.004) and low maximum percentage cancer in any core (P = 0.001) were predictors of downgrading. The authors conclude that men with a higher PSA level, perineural invasion, and high-volume cancer at biopsy are most likely to be upgraded, while men with a large prostate volume and low-volume cancer at biopsy are more likely to be downgraded. They note that these findings have implications for men with prostate cancer managed without confirmation of their true GS because PR was not the treatment elected.

Laudano et al. have investigated how frequently new information obtained at the time of surgery translates into a substantial change in the risk of recurrence for patients with localized prostate cancer, and to determine what factors contribute to this increase in risk. They used the Columbia Comprehensive Clinical Database of Urologic Oncology, to analyze data on 3,460 men who had radical prostatectomy (RP) for prostate cancer between 1988 and 2006. Kattan nomograms were used to calculate the 5-year progression-free probabilities before and after RP. The differences between these nomogram scores were used to divide the patients into three groups: those with a decrease in the probability of disease-free survival (DFS) of ≥ 15 percent; those with an increase in the probability of DFS of ≥ 15 percent, and those with an absolute change of < 15 percent. In all, 1,804 men with complete data before and after RP were analysed; 1,220 (68.4 percent) had no significant change in nomogram score; 238 (13.3 percent) had a significant increase; and 327 (18.3 percent) had a significant decrease in the probability of recurrence. The group with an increased probability of recurrence had a greater proportion of patients with pathological Gleason sum of ≥ 8, higher rates of extraprostatic capsular invasion, positive margins, seminal vesical invasion, and lymph node involvement (all P < 0.001). The authors conclude that risk predictions both before and after RP are central to effective patient counseling and optimal management. Of the patients in this study, 13.3 percent were faced with an increase of ≥ 15 percent in their risk of biochemical failure after pathological variables became available.

Filed under: Diagnosis, Management, Prevention, Treatment | Tagged: downgrading, Gleason, NSAID, pathological, risk, score, upgrading |