[show abstract][hide abstract] ABSTRACT: To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers.
The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds.
Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8-10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8-10 cancers would have been missed in the placebo group. In both groups, the incidence of Gleason 7 and Gleason 8-10 cancers generally increased with greater rises in PSA. Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7-10 cancers in men treated with dutasteride vs placebo. Men with Gleason 7 and Gleason 8-10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds.
Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8-10) or higher than (Gleason 7-10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.
BJU International 06/2011; 109(8):1162-9. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: Periodic Health Assessments have been mandated for United States Air Force servicemen since the mid 1990s. Thus, we determined whether United States Air Force prostate cancer incidence rates increased thereafter and how these tumors segregate into low and intermediate/high risk categories. We also identified treatment choices.
We queried the Department of Defense Automated Central Tumor Registry for prostate cancer diagnosed in United States Air Force servicemen between 1991 and 2008 to determine incidence rates, disease risk category and treatments.
Age adjusted rates in white active duty servicemen diagnosed for the most recent period of 2005 to 2008 increased 3-fold relative to the rate in the earliest period of 1991 to 1994. A similar trend was evident in black servicemen. Relative to the Surveillance, Epidemiology and End Results population prostate cancer rates in active duty United States Air Force men between 1995 and 2008 were significantly increased for the 2 racial groups. A significantly greater proportion of active duty servicemen than retirees (62% vs 40%) presented with low risk disease, defined as prostate specific antigen less than 10 ng/ml, Gleason sum less than 7 and clinical stage T1a-T2a. Of those with low risk disease significantly more active duty servicemen elected curative surgery than retirees (93% vs 53%).
Prostate cancer incidence rates in United States Air Force servicemen have increased with time, exceeding rates in the Surveillance, Epidemiology and End Results population. While most cases are characterized as low risk, aggressive management is elected.
The Journal of urology 06/2011; 185(6):2137-42. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess whether stress management (SM) improved immune outcomes in men undergoing surgery for prostate cancer.
A total of 159 men were assigned randomly to a two-session presurgical SM intervention, a two-session supportive attention (SA) group, or a standard care (SC) group. Men in the SM group discussed their concerns about the upcoming surgery and were taught diaphragmatic breathing, guided imagery; they had an imaginal exposure to the day of surgery and learned adaptive coping skills. Men in the SA group discussed their concerns about the upcoming surgery and had a semistructured medical interview. Blood samples were collected at baseline (1 month before surgery) and 48 hours after surgery. Measures of mood (Profile of Mood States) were collected at baseline, 1 week pre surgery, and the morning of surgery.
Men in the SM group had significantly higher levels of natural killer cell cytotoxicity (p = .04) and higher levels of circulating proinflammatory cytokines (interleukin [IL]-12p70, p = .02; IL-1β, p = .02; tumor necrosis factor-α, p = .05) 48 hours post surgery than men in the SA group and higher levels of natural killer cell cytotoxicity (p = 0.02) and IL-1β (p = .05) than men in the SC group. Immune parameters increased for the SM group and decreased or stayed the same for the SA and SC groups. The SM group had significantly lower Profile of Mood States scores than the SC group (p = .006), with no other group differences between SA and SC groups. Changes in mood were not associated with immune outcomes.
The finding that SM leads to decreased presurgical mood-disturbance and increased immune parameters after surgery reveals the potential psychological and biological benefits of presurgical SM.
Psychosomatic Medicine 01/2011; 73(3):218-25. · 4.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: We assessed whether dutasteride enhances the usefulness of total prostate specific antigen for diagnosing clinically significant prostate cancer.
The 4-year REDUCE study evaluated the efficacy and safety of 0.5 mg dutasteride daily for prostate cancer risk reduction in men with a prostate specific antigen of 2.5 to 10.0 ng/ml and a negative prostate biopsy. Specificity, sensitivity, and positive and negative predictive values of prostate specific antigen for the diagnosis of prostate cancer were assessed.
Final prostate specific antigen before biopsy and change from month 6 to final prostate specific antigen performed better for the diagnosis of Gleason score 7-10 tumors in men who received dutasteride vs placebo as assessed by the area under the ROC curves (0.700 vs 0.650, p = 0.0491; and 0.699 vs 0.593, p = 0.0001, respectively). Increases in prostate specific antigen were associated with a higher likelihood of biopsy detectable, Gleason score 7-10 and clinically significant (modified Epstein criteria) prostate cancer. Percentage decreases in prostate specific antigen from baseline to month 6 in the dutasteride arm did not predict prostate cancer overall or Gleason score 7-10 cancer.
In men with a previously negative prostate biopsy, prostate specific antigen performed better during the 4-year study as a marker of prostate cancer in men who received dutasteride vs placebo. The degree of prostate specific antigen increase after 6 months was a better indicator of clinically significant cancer in the dutasteride arm than in the placebo arm. Conversely, the initial decrease in prostate specific antigen in men taking dutasteride did not predict the likelihood of prostate cancer.
The Journal of urology 11/2010; 185(1):126-31. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the long-term outcomes of augmentation cystoplasty and continent catheterizable limb formation in patients who underwent simultaneous salvage prostatectomy.
Twelve men who underwent salvage prostatectomy with augmentation cystoplasty and either an appendicovesicostomy or Monti ileovesicostomy between October 2000 and February 2003 were assessed for long-term surgical complications, reoperations, continence rates, and patient satisfaction using the Incontinence Symptom Index (ISI) questionnaire and a self-designed catheterization questionnaire.
In addition to bladder augmentation, six patients underwent appendicovesicostomy, four had a Monti ileovesicostomy and two a spiral Monti ileovesicostomy. There were no intraoperative complications or surgical-related deaths. Four patients required revision surgery (33%) at a mean of 39 months. Minor revisions were performed for stomal stenosis in two patients with stomal relocation in two patients. Ten of 12 patients were dry (83.3%) with a catheterization frequency of between 3 and 8 hr. At a mean follow-up of 61 months (SD = 20.51), the mean ISI severity score was 1.86 (SD = 3.54) and the mean ISI bother score was 1 (SD 0.74). The majority (86%) would choose to undergo the surgery again.
Although surgically challenging and associated with significant morbidity, salvage prostatectomy with concomitant bladder augmentation and continent catheterizable reconstruction is a feasible and effective means of obtaining adequate long-term urinary continence, while preserving the native bladder. In comparison to similar historical patients with catheterizable limbs only, fewer of the augmented patients needed antimuscarinic medication and delayed augmentation was not necessary. Complications do not increase over time and the continence rates are stable.
[show abstract][hide abstract] ABSTRACT: To measure the time and subjective quality of individual steps of robot-assisted radical prostatectomy (RARP), as RARP performed by trainees has recently become the most common technique of RP in the USA, and although outcomes from expert surgeons are reported, limited data are available to document training experiences.
The patients studied were from a prospective cohort of 178 participants (124 with training data). Transperitoneal RARP was performed by one faculty surgeon and one assistant from a rotation of four urological oncology fellows and three residents. RARP was divided into 11 steps, and staff times were recorded for each step. Trainee times and quality scores were recorded for each step, the later defined as grade A equal to staff (A+, no verbal coaching); B, minor corrections; and C, major corrections. Short-term outcomes were recorded to assess the safety of the training.
The mean (range) console time/case of trainees was 40 (10-123) min. The median console time for a complete case by faculty and by trainees (pooled group) was 128 and 231 min, respectively, an increase in 81%. Individual trainee-performed steps increased in time (compared to staff) by a median range of 50-177%, and the incidence of quality grades < A of 9-100%. Trainee quality grades for basic tissue-dissection steps were higher than for advanced tissue dissection and suturing. There was no downgrading for a major correction. Analysis of short-term outcomes suggested acceptable results in a training environment. The study is limited by no available validated training measurement tools, and a low frequency of beginner trainees advancing to more difficult steps during the rotation.
During the initial exposure of trainees to RARP of <40 cases, we measured time and subjective quality grading of basic steps, and introduction to advanced steps. Training requires more procedure time, but does not appear to diminish expected outcomes.
BJU International 10/2009; 105(8):1148-54. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cytotoxic lymphocyte antigen-4 (CTLA-4) blockade is an active immunotherapeutic strategy that is currently in clinical trials in cancer. There are several ongoing trials of anti-CTLA-4 in the metastatic setting of prostate cancer patients with reported clinical responses consisting of decreases in the prostate specific antigen (PSA) tumor marker for some patients. Immunologic markers that correlate with these clinical responses are necessary to guide further development of anti-CTLA-4 therapy in the treatment of cancer patients. We recently reported that CD4(+) inducible co-stimulator (ICOS)(hi) T cells that produce interferon-gamma (IFN-gamma) are increased in the peripheral blood and tumor tissues of bladder cancer patients treated with anti-CTLA-4 antibody. Here we present data from the same clinical trial in bladder cancer patients demonstrating a higher frequency of CD4(+)ICOS(hi) T cells and IFN-gamma mRNA levels in nonmalignant prostate tissues and incidental prostate tumor tissues removed at the time of radical cystoprostatectomy. Our data suggest immunologic markers that can be used to monitor prostate cancer patients who receive anti-CTLA-4 therapy and indicate that the immunologic impact of anti-CTLA-4 antibody can occur in both tumor and nonmalignant tissues. These data should be taken into consideration for evaluation of efficacy as well as immune-related adverse events associated with anti-CTLA-4 therapy.
Proceedings of the National Academy of Sciences 03/2009; 106(8):2729-34. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: This review describes the morbidity of inguinal lymph node dissection (ILND) performed as part of the management of penile cancer as well as recent modifications that may reduce the incidence of complications.
A review of the literature was conducted using Pubmed for studies reporting complication outcomes of ILND for penile cancer. Furthermore, our contemporary results and patient related morbidity associated with ILND performed for penile cancer are reported and compared with prior series.
A review of the literature over the past 25 years identified 27 manuscripts discussing complications of ILND in the context of penile cancer. ILND has traditionally been associated with an 80-100% risk of surgical morbidity, with skin necrosis, wound dehiscence, infection, and lymphedema the predominant findings. Recent technical modifications and management strategies have reduced the associated risks of this surgical procedure. Most recently, we report a 19 and 27% rate of minor and major complications, respectively, for a diagnostic ILND (i.e., superficial ILND alone in the absence of nodal metastasis) and a 29 and 24% rate of minor and major complications, respectively, for a therapeutic ILND (superficial/deep ILND and pelvic lymph node dissection in the presence of nodal metastasis). In contrast, among clinically node negative patients undergoing dynamic sentinel lymph node biopsy as a staging procedure, the reported complication rate was 7%.
The incorporation of novel management strategies and surgical modifications have resulted in decreasing peri-operative morbidity associated with inguinal staging and therapy.
World Journal of Urology 10/2008; 27(2):205-12. · 2.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Center for Research on Minority Health (CRMH), the first Congressionally mandated center on minority health and health disparities outside of the Federal Government, conducts research that benefits the community. This project is a collaborative endeavor among the CRMH, M.D. Anderson's Department of Urology (Dr. Curtis Pettaway), and the Division of Cancer Prevention and Population Sciences. The funding has supported three interrelated, yet distinct efforts: (1) the CRMH infrastructure and its attendant research, educational, and community outreach activities; (2) research to examine prostate cancer screening and informed decision making in various ethnic groups; and (3) the M.D. Anderson Prostate Outreach Project (POP). Prostate cancer is the second leading cause of cancer mortality among men in the United States and significant ethnic disparities associated with prostate cancer and screening also persist. This project is expanding cutting edge research to ethnic minority communities and will result in new, culturally appropriate interventions to promote informed decision making in various ethnic groups. The POP model may facilitate further research with underserved communities and result in enhanced knowledge and potentially improved health outcomes.
[show abstract][hide abstract] ABSTRACT: Radical cystectomy is a major surgical procedure associated with significant blood loss and lengthy hospital stays. This surgical procedure is more challenging in women than men due to anatomical-based differences. We evaluated resource utilization and complication rates of patients undergoing radical cystectomy or exenteration using the Texas Hospital In-Patient Discharge Data Collection.
This was a retrospective study of 1,493 patients, 35 years of age or older, who underwent radical cystectomy for bladder cancer from January 2000 to December 2003. We evaluated blood product charges, length of stay, and complication rates during hospitalization.
In this sample, 24% of the patients (n = 356) were women. Overall, women had significantly increased blood product charges and length of stay compared to men, $1,392.87 vs. $718.21 (P < 0.001) and 12.72 vs. 11.64 (P = 0.03), respectively. During hospitalization, 26 of the patients died. No differences in mortality or complication rates were observed between men and women. Multivariate analysis showed that female sex (P < 0.001) and age (P = 0.003) were independent predictors of increased blood product charges. Multivariate analysis showed that female sex (P = 0.015), age (P = 0.003), and Charlson's comorbidity index >1 (P = 0.05) were predictors of longer length of stay.
Women and older patients with bladder cancer are at risk of increased blood products utilization and length of hospital stay after a radical cystectomy. Appropriate postoperative care and referrals should improve postoperative outcomes for these vulnerable patients.
International Urology and Nephrology 04/2008; 40(4):893-9. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: To develop a population-based clinical model of bladder cancer (BC) care costs and identify cost drivers.
We retrospectively reviewed a cohort of 4863 patients with BC identified from the linked Surveillance, Epidemiology and End Results-Medicare database, aged at least 65 years and diagnosed between 1994 and 1996. We collected the records of Medicare reimbursements (a surrogate of costs) through 1998 and classified them into clinically relevant intervals and care types by disease invasiveness to derive the cumulative costs of care. We calculated the incremental resource use costs using sex and age-matched controls from a 5% general population sample and compared similarly matched patients with other cancer (OC). We inflated all costs to 2006 U.S. dollars.
The annual cost of care for all patients with muscle-invasive BC (MIBC) was $35.72M (95% confidence interval $35.69M to $35.75M), 70% more than the $21.03M (95% confidence interval $21.00M to $21.05M) for patients with non-MIBC. The major cost drivers, regardless of disease stage, were diagnostic/surveillance and complications, accounting for up to 43% and 37% of BC care costs, respectively. Comorbidity-adjusted incremental annual resource costs per patient with MIBC were more than four times greater than those for patients with non-MIBC, similar to those of OC controls (P = 0.490-0.913), except for inpatient (P = 0.002) and hospice (P <0.001) costs, which were both statistically significantly lower. Annual adjusted incremental Medicare reimbursements totaled $36.3M for non-MIBC and $96.1 million for MIBC.
The results of this study have indicated that a reduction of BC care costs could be realized with strategies inhibiting disease progression and reducing the occurrence and severity of complications.
[show abstract][hide abstract] ABSTRACT: To measure knowledge of hereditary prostate cancer in a group of high-risk African American men.
Cross-sectional, correlational pilot study.
Four geographic sites: Detroit, MI; Houston, TX; Chicago, IL; and Columbia, SC.
79 men enrolled in the African American Hereditary Prostate Cancer Study.
Knowledge of hereditary prostate cancer.
Knowledge of hereditary prostate cancer was low.
The high percentage of incorrect responses on questions that measure genetic testing, prevention, and risk based on a positive family history highlights educational needs.
A critical need exists for nurses to educate high-risk African American men about hereditary prostate cancer.
Oncology Nursing Forum 08/2007; 34(4):854-60. · 1.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Prostate cancer patients on hormonal therapy experience significant treatment-related physical and psychological sequelae.
We examined moderator variables to determine whether certain participants demonstrated quality of life (QOL) benefits from a group-based lifestyle physical activity program compared to a group-based educational support program and standard care.
Participants were 134 prostate cancer patients on continuous androgen ablation in a controlled trial that used adaptive allocation.
As reported elsewhere, no significant differences were found between study conditions on primary QOL outcomes following the 6-month interventions. However, in a secondary analysis, several significant interactions indicated that both group programs benefited patients with lower psychosocial functioning at baseline; patients with lower mental health and social support scores had significant improvements in these measures compared with standard care. For those with higher pain, the educational support program resulted in significant improvements compared with the other two conditions. Twelve-month findings indicated lasting effects.
Consistent with existing research, results indicate that group interventions benefit cancer patients with limitations in psychosocial functioning. Findings underscore the importance of physical activity/exercise studies to employ control conditions that consider the attention and support provided by health educators and group members, particularly when examining psychosocial outcomes and pain.
Annals of Behavioral Medicine 03/2007; 33(1):99-104. · 4.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The African American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit families with early-onset disease fulfilling criteria of >or=4 affected.
We present a approximately 10 cM genome-wide linkage (GWL) analysis on 77 families including 254 affected and 274 unaffected genotyped.
Linkage analysis revealed three chromosomal regions with GENEHUNTER multipoint HLOD scores >or=1.3 for all 77 families at 11q22, 17p11, and Xq21. One family yielded genome-wide significant evidence of linkage (LOD = 3.5) to the 17p11 region with seven other families >or=2.3 in this region. Twenty-nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62 (alpha = 0.33) at the Xq21 locus. Two novel peaks >or=0.91 for the 16 families with '>6 affected' occurred at 2p21 and 22q12.
These chromosomal regions in the genome warrant further follow-up based on the hypothesis of multiple susceptibility genes with modest effects, or several major genes segregating in small subsets of families.
The Prostate 02/2007; 67(1):22-31. · 3.84 Impact Factor