Kang-Hsien Fan

Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer

BACKGROUND The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy. METHODS The Prostate Cancer Outcomes Study (PCOS) enrolled 3533 men in whom prostate cancer had been diagnosed in 1994 or 1995. The current cohort comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis. We used multivariable propensity scoring to compare functional outcomes according to treatment. RESULTS Patients undergoing prostatectomy were more likely to have urinary incontinence than were those undergoing radiotherapy at 2 years (odds ratio, 6.22; 95% confidence interval [CI], 1.92 to 20.29) and 5 years (odds ratio, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years. Similarly, although patients undergoing prostatectomy were more likely to have erectile dysfunction at 2 years (odds ratio, 3.46; 95% CI, 1.93 to 6.17) and 5 years (odds ratio, 1.96; 95% CI, 1.05 to 3.63), no significant between-group difference was noted at 15 years. Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (odds ratio, 0.39; 95% CI, 0.22 to 0.68) and 5 years (odds ratio, 0.47; 95% CI, 0.26 to 0.84), again with no significant between-group difference in the odds of bowel urgency at 15 years. CONCLUSIONS At 15 years, no significant relative differences in disease-specific functional outcomes were observed among men undergoing prostatectomy or radiotherapy. Nonetheless, men treated for localized prostate cancer commonly had declines in all functional domains during 15 years of follow-up. (Funded by the National Cancer Institute.).

Effect of Age, Tumor Risk, and Comorbidity on Competing Risks for Survival in a U.S. Population–Based Cohort of Men With Prostate Cancer

BACKGROUND Accurate estimation of life expectancy is essential to offering appropriate care to men with early-stage prostate cancer, but mortality risks associated with comorbidity are poorly defined. OBJECTIVE To determine the effect of age, comorbidity, and tumor risk on other-cause and prostate cancer-specific mortality in men with early-stage disease. DESIGN Prospective cohort study. SETTING A nationally representative, population-based cohort. PATIENTS 3183 men with nonmetastatic prostate cancer at diagnosis. MEASUREMENTS Baseline self-reported comorbidity (scored as a count of 12 major comorbid conditions), tumor characteristics, initial treatment, and overall and disease-specific mortality through 14 years of follow-up. Survival analyses that accounted for competing risks were performed. RESULTS Fourteen-year cumulative other-cause mortality rates were 24%, 33%, 46%, and 57% for men with 0, 1, 2, and 3 or more comorbid conditions, respectively. For men diagnosed at age 65 years, subhazard ratios for other-cause mortality among those with 1, 2, or 3 or more comorbid conditions (vs. none) were 1.2 (95% CI, 1.0 to 1.4), 1.7 (CI, 1.4 to 2.0), and 2.4 (CI, 2.0 to 2.8), respectively. Among men with 3 or more comorbid conditions, 10-year other-cause mortality rates were 26%, 40%, and 71% for those aged 60 years or younger, 61 to 74 years, and 75 years or older at diagnosis, respectively. Prostate cancer-specific mortality was minimal in patients with low-risk (3%) and intermediate-risk (7%) disease but appreciable in those with high-risk disease (18%) and did not vary by number of comorbid conditions (10% to 11% in all groups). LIMITATION Comorbid conditions were self-reported. CONCLUSION Older men with multiple major comorbid conditions are at high risk for other-cause mortality within 10 years of diagnosis and should consider this information when deciding between conservative management and aggressive treatment for low- or intermediate-risk prostate cancer. PRIMARY FUNDING SOURCE National Cancer Institute.

Mortality After Radical Prostatectomy or External Beam Radiotherapy for Localized Prostate Cancer

BACKGROUND No randomized trials have compared survival outcomes for men with localized prostate cancer (PC) being treated with radical prostatectomy (RP) or external beam radiotherapy (EBRT). The goal of the study, therefore, was to estimate the association of RP (compared with EBRT) with overall and PC mortality. METHODS We analyzed an observational cohort from the population-based Prostate Cancer Outcomes Study, which included men aged 55 to 74 years diagnosed with localized PC between October 1994 and October 1995 who underwent either RP (n = 1164) or EBRT (n = 491) within 1 year of diagnosis. Patients were followed until death or study end (December 31, 2010). Overall and disease-specific mortality were assessed with multivariable survival analysis, with propensity scores to adjust for potential treatment selection confounders (demographics, comorbidities, and tumor characteristics). All statistical tests were two-sided. RESULTS After 15 years of follow-up, there were 568 deaths, including 104 from PC. RP was associated with statistically significant advantages for overall (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.53 to 0.70, P <.0001.) and disease-specific mortality (HR = 0.35, 95% CI = 0.26 to 0.49, P <.0001.). Mortality benefits for RP were also observed within treatment propensity quintiles, when subjects were pair-matched on propensity scores, and in subgroup analyses based on age, tumor characteristics, and comorbidity. CONCLUSIONS Population-based observational data on men diagnosed with localized PC in the mid-1990s suggest a mortality benefit associated with RP vs EBRT. Possible explanations include residual selection bias or a true survival advantage. Results might be less applicable for men facing treatment decisions today.

Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study

Background:To assess the relationship between androgen deprivation therapy (ADT) exposure and self-reported bone complications among men in a population-based cohort of prostate cancer survivors followed for 15 years after diagnosis.Methods:The Prostate Cancer Outcomes Study enrolled 3533 patients diagnosed with prostate cancer between 1994 and 1995. This analysis included participants with non-metastatic disease at the time of diagnosis who completed 15-year follow-up surveys to report development of fracture, and use of bone-related medications. The relationship between ADT duration and bone complications was assessed using multivariable logistic regression models.Results:Among 961 surviving men, 157 (16.3%) received prolonged ADT (>1 year), 120 (12.5%) received short-term ADT (⩽1 year) and 684 (71.2%) did not receive ADT. Men receiving prolonged ADT had higher odds of fracture (OR 2.5; 95% confidence interval (CI): 1.1–5.7), bone mineral density testing (OR 5.9; 95% CI: 3.0–12) and bone medication use (OR 4.3; 95% CI: 2.3–8.0) than untreated men. Men receiving short-term ADT reported rates of fracture similar to untreated men. Half of men treated with prolonged ADT reported bone medication use.Conclusions:In this population-based cohort study with long-term follow-up, prolonged ADT use was associated with substantial risks of fracture, whereas short-term use was not. This information should be considered when weighing the advantages and disadvantages of ADT in men with prostate cancer.

Bone health among prostate cancer survivors: Long-term follow-up from the Prostate Cancer Outcomes Study (PCOS).

106 Background: Bone complications of androgen deprivation therapy (ADT) have been described using administrative databases and smaller prospective studies with relatively short follow-up. Prospectively acquired data with long term follow-up are lacking. We assessed the relationship of patient-reported bone health and ADT exposure in a population-based prospective cohort of prostate cancer survivors followed longitudinally for 15 years from diagnosis. METHODS Using PCOS 15 year patient-reported survey data, we identified men with non-metastatic prostate cancer diagnosed from 1994-1995 and followed through 2009-2010. We evaluated subgroups receiving >1 yr, ≤1 yr, and no ADT. We then queried participants regarding the development of osteoporosis, fracture, and use of osteoporosis medications. We assessed the relationship between duration of ADT and bone health outcomes using univariable logistic regression models, and evaluated the association between ADT and osteoporosis medications using multivariable logistic regression adjusted for PSA and geographic location. RESULTS Among 961 men who completed 15 year surveys, 157 received >1 yr ADT, 120 received ≤1 yr ADT, and 684 did not receive ADT. During the study period, 12 men developed bone metastases and were excluded from the fracture analysis (7 received >1 yr ADT, 2 received ≤1 yr ADT, and 3 did not receive ADT). Men receiving >1 yr ADT were more likely to report osteoporosis (OR 4.29, 95% CI 2.38-7.71) or fracture (OR 1.73, 95% CI 1.04-2.89) than men not receiving ADT. When compared with men not receiving ADT, men receiving >1 yr ADT were more likely to report bone mineral density testing (OR 4.59, 95% CI 3.09-6.83), and bone medication use (OR 3.22, 95% CI 2.19-4.72). Half (50.3%) of men treated for >1 yr ADT reported bone medication use. Among men who reported use of bone medications, 94% reported calcium or vitamin D use and 6% reported bisphosphonate use. CONCLUSIONS Men treated with prolonged ADT (>1 yr) reported higher rates of osteoporosis and fracture at 15 year follow up. Accordingly, they reported more frequent screening and treatment for osteoporosis, with 50% of men receiving prolonged ADT reporting use of bone medications.

136 INFLUDENCE OF RACE AND COMORBIDITY ON THERAPY FOR PROSTATE CANCER: EVOLUTION OVER 15 YEARS

these terms, especially among underserved populations. We hypothesized that a video-based educational tool would significantly improve understanding of these key terms related to prostate health among a predominantly lower-literacy population. METHODS: A software application was developed by various experts, including urologists and human-computer interaction specialists, to serve as the video-based educational tool, emphasizing animations to promote understanding. A previously developed survey was used to evaluate comprehension of terms related to urinary, bowel, and sexual function. Trained interviewers provided the survey to patients from two low-income safety-net clinics both before and after administration of the educational tool. Preand post-intervention levels of comprehension were assessed using semi-qualitative methods coded by two independent evaluators. RESULTS: 56 patients completed the study, with a mean literacy level of 7th to 8th grade by literacy testing, but a self-reported mean education level of 12th grade. Patients achieved statistically significant improvement in comprehension for the majority of the terms after the video intervention (see Table). Notable improvements in understanding were exhibited for the terms ?rectal urgency’ (18% to 73%, P-value 0.000001), ‘incontinence’ (from 14% to 50%, P-value 0.000035), and ‘bowel’ (14% to 46%, P-value 0.0001). Patients also demonstrated significant gains in understanding of the function of the prostate (11% to 30%, P-value 0.0074). CONCLUSIONS: The video-based educational tool is an effective method for combatting the severe lack of comprehension of prostate health terminology among this population, which may be reflective of many patients overall. The improvements in understanding achieved with this intervention have the potential to enhance patient participation in shared and informed decision-making. These results support combined visual and audio multimedia as a promising tool for prostate cancer education and thus as an area for further research and refinement.

449 THE BURDEN OF PRE-TREATMENT URINARY, SEXUAL, AND BOWEL DYSFUNCTION ACROSS TWO DECADES OF PROSTATE CANCER: RESULTS FROM PCOS AND CEASAR

Source of Funding: This study was supported by the National Cancer Institute, National Institutes of Health, Bethesda, MD, through grant #R01-CA114524 and the following contracts from the each of the participating institutions: N01-PC-67007, N01PC-67009, N01-PC-67010, N01-PC-67006, N01-PC-67005, and N01-PC-67000. Dr. Resnick was supported by the Veterans Affairs National Quality Scholars Program with use of facilities at Veterans Health Administration Tennessee Valley Healthcare System and additionally by the T.J. Martell Foundation.

686 SURVIVAL OUTCOMES FOLLOWING SURGERY OR RADIATION FOR LOCALIZED PROSTATE CANCER RESULTS FROM THE PROSTATE CANCER OUTCOMES STUDY

INTRODUCTION AND OBJECTIVES: No randomized trials have compared survival outcomes for men with localized prostate cancer (PCa) being treated with surgery or radiotherapy. The purpose of our analysis was to compare 15-year overall and prostate-cancer survival in a population-based cohort of men with localized PCa treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). METHODS: The Prostate Cancer Outcomes Study (PCOS) enrolled patients with prostate cancer diagnosed between October 1994 and October 1995. The study cohort for the current analysis was comprised of the men ages 55 to 74 years when diagnosed with localized cancer who underwent either RP or EBRT within 1 year of diagnosis. Baseline measures included demographics, socioeconomic status, comorbidity, tumor characteristics, and treatment. We used data from the SEER program and the National Death Index to determine date and cause of death through December 2010. Men receiving surgery may be younger, healthier, and have more favorable tumor characteristics than those receiving radiation treatment. Therefore, in addition to restricting age range, we attempted to control for treatment selection bias by using a propensity score analysis. We used multivariate proportional hazards regression models with baseline measures and propensity score as covariates to compare overall and diseasespecific survival following RP and EBRT. RESULTS: The study cohort comprised 1,655 men, of whom 1164 (70.3%) underwent RP and 491 (29.7%) underwent EBRT. Overall, there were 320 deaths (27%) in the surgical cohort, including 45 (3.9%) from prostate cancer. Among men undergoing EBRT, there were 248 (51%) deaths, including 59 (12%) from PCa. On multivariate survival analysis, the hazard ratio (HR) for overall survival was significantly lower for men undergoing EBRT compared to RP, HR 0.60, 95% CI 0.53-0.70). We also found significantly lower disease-specific survival (HR 0.35, 95% CI 0.26-0.49) for men undergoing EBRT. Men undergoing EBRT had poorer disease-specific survival when we restricted analyses to those younger than 65 (HR 0.18, 95% CI 0.11-0.32) or to those with high-risk cancers (PSA 10, Gleason iÝ 8) who underwent either RP or EBRT with combined androgen deprivation therapy (HR 0.42, 95 CI, 0.22-0.79). CONCLUSIONS: Although the potential for unadjusted confounding still exists, observational population-based data suggested that overall and disease-specific survival among men diagnosed with localized PCa in 1994-5 were significantly improved following receipt of RP compared to EBRT.