Tracy M. Downs

Racial/Ethnic and Gender Disparities in Renal Cell Carcinoma Incidence and Survival

PURPOSE We used a population based cancer registry to examine trends in renal cell carcinoma incidence and survival among 4 racial/ethnic groups (white, black, Hispanic and Asian/Pacific Islander) and both genders. MATERIALS AND METHODS Race/ethnicity, gender, age, staging, length of survival and cause of death data were analyzed using 39,434 cases of renal cell carcinoma from 1988 to 2004 from the California Cancer Registry. Annual age adjusted incidence rates and relative survival rates were calculated for the racial/ethnic and gender groups. These rates and the percent of localized cancer were plotted by year, and Microsoft Excel was used to calculate linear regression equations. Median age was also calculated. Z-tests and chi-square tests were performed to determine p values. RESULTS An increase in renal cell carcinoma incidence was found with localized cancer accounting for most of the increase. Black patients had a significantly higher incidence rate (p <0.0001) and lower survival rate (p <0.0001) than all other races/ethnicities despite having more localized cancer (p <0.005). Black patients were also diagnosed at a younger age (p <0.0001) than their counterparts. On the other hand Asian/Pacific Islanders had a lower incidence rate (p <0.0001) and higher survival rate (p <0.05) than all other races/ethnicities. Males had approximately twice the incidence rate of females and a lower survival rate (p <0.005). CONCLUSIONS Higher incidence rates and lower survival rates were identified among black and male patients compared to their counterparts, while Asian/Pacific Islanders showed the opposite trends. Such racial/ethnic and gender disparities in renal cell carcinoma incidence and survival may help elucidate biological, behavioral and environmental factors that can potentially be addressed.

Profiling alternatively spliced mRNA isoforms for prostate cancer classification

BackgroundProstate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification.ResultsAs many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account.ConclusionThese results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays.

WATCHFUL WAITING AND HEALTH RELATED QUALITY OF LIFE FOR PATIENTS WITH LOCALIZED PROSTATE CANCER: DATA FROM CaPSURE

PURPOSE Watchful waiting is an alternative to active treatment for men with low risk prostate cancer but it is unclear how health related quality of life (HRQoL) may change over time for men who select this option. We report on HRQoL in men with localized prostate cancer who selected watchful waiting. MATERIALS AND METHODS HRQoL outcomes were reviewed for 310 men diagnosed with prostate cancer from 1990 to 2001 within Cancer of the Prostate Strategic Urological Research Endeavor who chose watchful waiting. The UCLA Prostate Cancer Index and RAND 36-Item Health Survey were completed at enrollment and approximately every 6 months. A random slopes model was developed to assess time trends in HRQoL for up to 5 years after diagnosis, adjusting for age at diagnosis and specific comorbidities. RESULTS Significant decreases with time were observed in 7 domains of the RAND 36-Item Health Survey and 4 of the UCLA Prostate Cancer Index scales. CONCLUSIONS Men with prostate cancer who chose watchful waiting in the current study had better or similar HRQoL outcomes compared to men without prostate cancer at the start of the study. Many of these scores were significantly affected by increasing age and decreased with time. The physical domain scores as well as sexual function scores decreased more than expected from the aging process alone.

Prostate bed localization with image-guided approach using on-board imaging: Reporting acute toxicity and implications for radiation therapy planning following prostatectomy

OBJECTIVES To report our experience using Image-Guided Radiation Therapy (IGRT) in patients undergoing post-prostatectomy irradiation. METHODS Twenty-six patients were treated with radiotherapy following radical prostatectomy using Intensity Modulated Radiation Therapy (IMRT). Prostate bed localization was done using image guidance to align surgical clips relative to the reference isocenter on the planning digitally reconstructed radiographs. Assuming surgical clips to be surrogate for prostate bed, daily shifts in their position were calculated after aligning with the bony anatomy. Shifts were recorded in three dimensions. The acute toxicity was measured during and after completion of treatment. RESULTS The average (standard deviation) prostate bed motion in anterior-posterior, superior-inferior and left-right directions were: 2.7mm (2.1), 2.4mm (2.1) and 1.0mm (1.7), respectively. The majority of patients experienced only grade 1 symptoms, two patients had grade 2 symptoms and none had grade 3 or higher acute toxicity. CONCLUSIONS Daily IGRT is recommended for accurate target localization during radiation delivery to improve efficacy of treatment and enhance therapeutic ratio. Larger studies with longer follow-up are necessary to make definitive recommendations regarding magnitude of margin reduction around clinical target volume.

Is ethnicity an independent predictor of prostate cancer recurrence after radical prostatectomy

PURPOSE Prostate cancer incidence and mortality are higher in black than in white American men. We determined whether ethnicity is an independent predictor of disease recurrence in men undergoing radical prostatectomy. MATERIALS AND METHODS We studied 1,468 patients who underwent radical prostatectomy at the University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor database, a longitudinal disease registry of patients with prostate cancer. Preoperative characteristics, including age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage, biopsy Gleason score and percent positive prostate biopsies at diagnosis were determined in each patient. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment at least 6 months after surgery. Cox proportional hazards analysis was performed to determine independent predictors of time to disease recurrence. To control for pretreatment disease characteristics simultaneously patients were assigned to previously described risk groups based on clinical tumor stage, PSA at diagnosis and biopsy Gleason score. The likelihood of disease recurrence per risk group stratified according to ethnicity was determined using the Kaplan-Meier method and compared using the log rank test. Additional multivariate analysis was performed in the subset of patients enrolled in Cancer of the Prostate Strategic Urological Research Endeavor on whom education and income information was available. RESULTS Disease recurred in 304 of the 1,468 patients (21%). Black ethnicity, serum PSA at diagnosis, biopsy Gleason score and percent positive prostate biopsies were independent predictors of recurrence on multivariate analysis. Black ethnicity remained an independent predictor of disease recurrence in the multivariate model after stratifying patients into risk groups (p = 0.0007). Ethnicity was most important in patients at high risk, in whom estimated 5-year disease-free survival was 65% and 28% in white and black men, respectively. Education, income and ethnicity correlated highly. When education and income were entered into the multivariate model, ethnicity was no longer an independent predictor of outcome after prostatectomy. CONCLUSIONS Ethnicity appears to be an independent predictor of disease recurrence after adjusting for pretreatment measures of disease extent in patients undergoing radical prostatectomy. It appears to be particularly important in those with high risk disease characteristics. However, black ethnicity, education and income are highly correlated variables, suggesting that sociodemographic factors may contribute to the poorer outcomes in black patients even after adjusting for differences in pretreatment disease characteristics.

Late age (85 years or older) peak incidence of bladder cancer.

PURPOSE We examined the incidence rates of bladder cancer using California Cancer Registry data to determine if any trends exist. MATERIALS AND METHODS Complete records of the 55,159 cases of invasive bladder cancer were examined from the original 92,677 bladder cancer cases recorded in the California Cancer Registry between 1988 and 2004. RESULTS California Cancer Registry data showed a universal late age peak in age specific incidence of bladder cancer in men and women, and across ethnic boundaries. The rate of annual increase in the percent of bladder cancer in individuals 85 years or older was increasing about 10 times as rapidly as the percent of the population that was 85 years or older (slope = 0.395 vs 0.0336). Furthermore, during all 17 years the proportion of patients 85 or older with bladder cancer was about twice that of patients with other cancers regardless of gender. CONCLUSIONS California Cancer Registry data illustrate a peak in the incidence of bladder cancer in individuals 85 years or older. However, to our knowledge there is no known explanation for this late peak in bladder cancer. With the rate of bladder cancer in the population 85 years or older increasing at a rapid pace, it is critical to encourage investigators to include this age group as they continue to search for causative factors and genetic contributors to bladder cancer as well as effective treatments.

Penile injection with silicone: case report and review of the literature.

INTRODUCTION Liquid injectable silicone (LIS) has been used for soft tissue augmentation in excess of 50 years. Until recently, all literature on penile augmentation with LIS consisted of case reports or small cases series, most involving surgical intervention to correct the complications of LIS. New formulations of LIS and new methodologies for injection have renewed interest in this procedure. AIM We reported a case of penile augmentation with LIS and reviewed the pertinent literature. METHODS Comprehensive literature review was performed using PubMed. We performed additional searches based on references from relevant review articles. RESULTS Injection of medical grade silicone for soft tissue augmentation has a role in carefully controlled study settings. Historically, the use of LIS for penile augmentation has had poor outcomes and required surgical intervention to correct complications resulting from LIS. CONCLUSIONS We currently discourage the use of LIS for penile augmentation until carefully designed and evaluated trials have been completed.

Impact of patient educational level on treatment for patients with prostate cancer: data from CaPSURE.

OBJECTIVES To examine the effect of a patients educational level on treatment selection for patients with newly diagnosed prostate cancer. A patients educational level may impact a patients understanding and perception of the risks and benefits of the treatment options for prostate cancer. METHODS We examined 3484 patients in CaPSURE with prostate cancer between 1992 and 2001. Chi-square and multinomial logistic regression analyses were performed to determine the role of education level in primary treatment received relative to other pretreatment predictors (age, race, insurance status, prostate cancer risk, comorbidity). Prostate cancer risk stratification was determined by serum prostate-specific antigen level and tumor stage and grade. RESULTS The mean patient age was 67.7 +/- 8.3 years, and the mean prostate-specific antigen level was 13.0 +/- 18.7 ng/mL. Of the 3484 patients, 16.7% had less than a high school education, 27.0% had completed high school or technical school, 19.5% had had some college, 18.0% had graduated from college, and 18.6% had had some graduate education. In bivariate analysis, the factors predictive of treatment selection were patient age, race, education, insurance status, risk group, and patient comorbidity (all P <0.001). In multinomial regression analysis, the factors predicting treatment received were age, race, cancer risk group, and comorbidity. For patients older than 75 years, those with a higher education level received more aggressive treatment (radiotherapy versus hormonal therapy) than did those with less education. CONCLUSIONS Patient age, race, cancer risk group, comorbidity, and, for men older than 75 years, education level are the factors predictive of the primary treatment received by men with newly diagnosed prostate cancer.

Potential Attenuation of Disease Progression in Recurrent Prostate Cancer With Plant-Based Diet and Stress Reduction:

A rising level of prostate-specific antigen (PSA), after primary surgery or radiation therapy, is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise asymptomatic. While hormonal therapy may slightly extend survival in a minority of patients, it is not curative and produces side effects including hot flashes, decreased libido, and loss of bone mass. Alternatively, dietary modification may offer an important tool for clinical management. Epidemiologic studies have associated the Western diet not only with prostate cancer incidence but also with a greater risk of disease progression after treatment. Conversely, many elements of plant-based diets have been associated with reduced risk of progression. However, dietary modification can be stressful and difficult to implement. We therefore conducted a 6-month pilot clinical trial to investigate whether adoption of a plant-based diet, reinforced by stress management training, could attenuate the rate of further PSA rise. Urologists at the University of California, San Diego, and San Diego Veterans Affairs Medical Centers recruited 14 patients with recurrent prostate cancer. A pre-post design was employed in which each patient served as his own control. Rates of PSA rise were ascertained for each patient for the following periods: from the time of posttreatment recurrence up to the start of the study (prestudy) and from the time immediately preceding the intervention (baseline) to the end of the intervention (0-6 months). There was a significant decrease in the rate of PSA rise from prestudy to 0 to 6 months ( P < .01). Four of 10 evaluable patients experienced an absolute reduction in their PSA levels over the entire 6-month study. Nine of 10 had a reduction in their rates of PSA rise and an improvement of their PSA doubling times. Median PSA doubling time increased from 11.9 months (prestudy) to 112.3 months (intervention). These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for clinical management of recurrent prostate cancer.

Personality predicts prostate cancer treatment decision-making difficulty and satisfaction.

Objective: Prostate cancer (PCa) patients often must decide between several treatment modalities considered equally efficacious, but associated with different benefits and side‐effects. For some, the decision‐making process can be difficult, but little is known about patient characteristics and cognitive processes that might influence the difficulty of such decisions. This study investigated the roles of dispositional optimism and self‐efficacy in PCa treatment decision‐making difficulty and satisfaction.