Faculty Bibliography

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

PURPOSE: The authors describe their initial experience in implementing an integrated radiology reading room within a urologic oncology clinic, including the frequency and nature of clinician consultations and the perceived impact on patient management by clinicians. METHODS: A radiology reading room was established within an office-based urologic oncology clinic in proximity to the surgeon's work area. A radiologist was present in this reading room for a 3-hour shift each day. The frequency and nature of consultations during these shifts were recorded. Also, the clinic's staff completed a survey assessing perceptions of the impact of the integrated reading room on patient management. RESULTS: One hundred two consultations occurred during 57 included dates (average, 1.8 consultations per shift): 52% for review of external cases brought in by patients on discs, 43% for review of internal cases, and 5% for direct review by the radiologist of imaging with patients. The maximum number of consultations during a single shift was 8. All of the clinic's urologists indicated that >90% of consultations benefited patient care. The clinicians indicated tendencies to view consultations as affecting management in the majority of cases, to be more likely to seek consultation for outside imaging when the radiologist was on site, and to be less likely to repeat outside imaging when the radiologist was on site. CONCLUSIONS: The integrated reading room within the clinic has potential to improve the quality of care, for instance by facilitating increased review of outside imaging studies and thereby potentially reducing duplicate ordering and by enabling occasional direct image review with patients by radiologists.

PURPOSE: The prevalence of lower urinary tract symptoms increases with age and impairs quality of life. Radical prostatectomy has been shown to relieve lower urinary tract symptoms at short-term followup but the long-term effect of radical prostatectomy on lower urinary tract symptoms is unclear. MATERIALS AND METHODS: We performed a prospective cohort study of 1,788 men undergoing radical prostatectomy. The progression of scores from the self-administered AUASS (American Urological Association symptom score) preoperatively, and at 3, 6, 12, 24, 48, 60, 84, 96 and 120 months was analyzed using models controlling for preoperative AUASS, age, prostate specific antigen, pathological Gleason score and stage, nerve sparing, race and marital status. This model was also applied to patients stratified by baseline clinically significant (AUASS greater than 7) and insignificant (AUASS 7 or less) lower urinary tract symptoms. RESULTS: Men exhibited an immediate worsening of lower urinary tract symptoms that improved between 3 months and 2 years after radical prostatectomy. Overall the difference between mean AUASS at baseline and at 10 years was not statistically or clinically significant. Men with baseline clinically significant lower urinary tract symptoms experienced immediate improvements in lower urinary tract symptoms that lasted until 10 years after radical prostatectomy (13.5 vs 8.81, p <0.001). Men with baseline clinically insignificant lower urinary tract symptoms experienced a statistically significant but clinically insignificant increase in mean AUASS after 10 years (3.09 to 4.94, p <0.001). The percentage of men with clinically significant lower urinary tract symptoms decreased from baseline to 10 years after radical prostatectomy (p = 0.02). CONCLUSIONS: Radical prostatectomy is the only treatment for prostate cancer shown to improve and prevent the development of lower urinary tract symptoms at long-term followup. This previously unrecognized long-term benefit argues in favor of the prostate as the primary contributor to male lower urinary tract symptoms.

Autopsy studies of men without known prostate cancer suggest that a substantial reservoir of prostate cancer that does not cause symptoms or death exists within the population. The majority of these cancers are Gleason 6 tumors and are frequently detected by prostate-specific antigen-based prostate cancer screening.There is strong evidence from longitudinal cohort studies of men with both treated and untreated Gleason 6 prostate cancer to suggest that Gleason 6 disease, when not associated with higher-grade cancer, virtually never demonstrates the ability to metastasize and thus represents an indolent entity that does not require treatment. Whether Gleason 6 has a propensity to progress to higher-grade cancer is still under investigation. Because the term "cancer" has historically been used to represent a disease state that leads to progressive illness that is uniformly fatal without treatment, we believe Gleason 6 disease should not be labeled with this term. Our challenge now is to develop the technology to differentiate true Gleason 6 disease from the higher grades of dysplasia with which it can be associated.

BACKGROUND: Urinary incontinence is a common short-term complication of radical prostatectomy (RP). Little is known about the long-term impact of RP on continence. OBJECTIVE: To elucidate the long-term progression of continence after RP. DESIGN, SETTING, AND PARTICIPANTS: From October 2000 through September 2012, 1788 men undergoing open RP for clinically localized prostate cancer by a single surgeon at an urban tertiary care center prospectively signed consent to be followed before RP and at 3, 6, 12, 24, 96, and 120 mo after RP. A consecutive sampling method was used and all men were included in this study. INTERVENTION: Men underwent open RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression models controlled for preoperative University of California, Los Angeles-Prostate Cancer Index urinary function score (UCLA-PCI-UFS), age, prostate-specific antigen level, Gleason score, stage, nerve-sparing status, race, and marital status were used to evaluate the association of time since RP with two dependent variables: UCLA-PCI-UFS and continence status. RESULTS AND LIMITATION: The mean UCLA-PCI-UFS declined between 2 yr and 8 yr (83.8 vs 81.8; p=0.007) and marginally between 8 yr and 10 yr (81.8 vs 79.6; p=0.036) after RP, whereas continence rate did not significantly change during these intervals. Men >/=60 yr old experienced a decline in mean UCLA-PCI-UFS between 2 yr and 8 yr (p=0.002) and a marginal decline in continence rate between 2 yr and 10 yr (p=0.047), whereas these variables did not change significantly in men <60 yr old. These outcomes are for an experienced surgeon, so caution should be exercised in generalizing these results. CONCLUSIONS: Between 2 yr and 10 yr after RP, there were slight decreases in mean UCLA-PCI-UFS and continence rates in this study. Men aged <60 yr had better long-term outcomes. These results provide realistic long-term continence expectations for men undergoing RP.

BACKGROUND: The long-term impact of radical prostatectomy (RP) on sexual function (SF) and erectile function (EF) has important implications related to the risk-to-benefit ratio of this treatment. OBJECTIVE: To determine the long-term effect of RP on male SF and EF over 10 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, longitudinal outcomes study in 1836 men following RP at a university hospital. Men were invited to complete the University of California, Los Angeles, Prostate Cancer Index SF survey at baseline, 3, 6, 12, 24, 96, and 120 mo postoperatively and a survey at 4 and 7 yr postoperatively assessing global changes in their EF over the preceding 2 yr. INTERVENTION: All men underwent open RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multiple, generalized linear regression models were used to evaluate the association between time following RP and SF and EF scores controlling for age, prostate-specific antigen, Gleason scores, stage, nerve sparing, race, and marital status. RESULTS AND LIMITATIONS: After an expected initial decline, time-dependent improvements in SF and EF were observed through 2 yr postoperatively. Overall, SF and EF were both generally stable between 2 and 10 yr following RP. The subgroups of younger men and men with better preoperative function were more likely to maintain their EF and SF through 10 yr following RP. The primary limitation is the potential bias attributable to nonresponders. CONCLUSIONS: The recovery of EF can extend well beyond 2 yr. There is a significant association between younger age and better preoperative function and the likelihood of experiencing improvements beyond 2 yr. Assessing the comparative effectiveness of treatment options for localized prostate cancer must examine SF beyond 2 yr to account for delayed treatment effects and the natural history of SF in the aging male population.

Focal therapy of prostate cancer is an evolving treatment strategy that destroys a predefined region of the prostate gland that harbors clinically significant disease. Although long-term oncologic control has yet to be demonstrated, focal therapy is associated with a marked decrease in treatment-related morbidity. Focal laser ablation is an emerging modality that has several advantages, most notably real-time magnetic resonance imaging (MRI) compatibility. This review presents the principles of laser ablation, the role of multiparametric MRI for delineating the site of significant prostate cancer, a summary of published clinical studies, and our initial experience with 23 patients, criteria for selecting candidates for focal prostate ablation, and speculation regarding future directions.