Thomas E Keane

Medical University of South Carolina, Charleston, South Carolina, United States

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Publications (69)199.41 Total impact

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    ABSTRACT: Prostate cancer (PCa) is one of the most common cancers diagnosed in men in the United States, and approximately 20% to 30% of men treated for localized PCa will fail therapy and develop advanced PCa More drugs have been approved for the treatment of advanced PCa in the past three years than in the past three decades, and each drug has its own mechanism of action and, often, unique monitoring requirements Since the treatment landscape for men with advanced PCa is undergoing significant expansion, the roles of both oncologists and urologists are shifting, and the decision for the urologist to treat versus refer requires early assessment to identify which patients are candidates for these novel treatments and the monitoring of patients for tolerability, response, and potential side effects Given these rapid changes, the authors of this review met in January 2013 and again in April 2013 to discuss the current challenges facing urologists in adopting these new treatments into their own practices Here, we provide a brief overview of advanced PCa medical therapies approved in the past decade, the necessary monitoring procedures and early detection methods needed to safely and effectively manage patients receiving these therapies, and our recommendations for applying these new therapies within different models of urology practice such that urologists can remain an integral component of their patient's care once he has transitioned into advanced Pca
    BJU International 02/2014; · 3.05 Impact Factor
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    ABSTRACT: Prostate cancer is often associated with metastases to bone and/or soft tissue. The progression to metastatic castrate-resistant prostate cancer is a seminal event in disease progression affecting treatment decisions. A multidisciplinary group was convened to review the currently available imaging guidelines for metastatic disease in prostate cancer and found no consensus on eligibility criteria, type of imaging modality, and the frequency of scanning for detecting metastatic disease. The aim of this review was to present the recommendations from the group to identify optimal strategies for early identification of metastases in patients with prostate cancer.
    Urology 01/2014; · 2.42 Impact Factor
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    Thomas E Keane
    World Journal of Urology 11/2013; · 2.89 Impact Factor
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    ABSTRACT: This was a phase I study to find the maximum tolerable dose (MTD) of weekly docetaxel combined with high-dose intensity-modulated radiotherapy (IMRT) and androgen deprivation therapy (ADT). Men with localized high-risk prostate cancer (HRPC) were treated with weekly docetaxel at 10 to 30 mg/m(2) concurrent with IMRT of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before and during chemoradiation. GnRHa was continued for 24 months. Nineteen patients were enrolled. No dose-limiting toxicity (DLT) was seen with docetaxel doses up to 25 mg/m(2). At the 30 mg/m(2) level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and dyspepsia. At 41 months' median follow-up, 2 patients had died-1 from metastatic prostate cancer and the other from heart failure. Two other patients experienced biochemical failure. One patient with bladder invasion at diagnosis experienced late grade 2 urinary hesitancy 9 months after completion of radiotherapy, requiring short-term intermittent catheterization. All patients had erectile dysfunction, but no late toxicities worse than grade 2 were identified. Weekly docetaxel may be combined with high-dose IMRT and long-term ADT up to a MTD of 25 mg/m(2). Acute toxicities and long-term side effects of this regimen were acceptable. Future studies evaluating the efficacy of docetaxel, ADT, and IMRT for localized HRPC should use a weekly dose of 25 mg/m(2) when limiting the irradiated volume to the prostate and seminal vesicles.
    Clinical Genitourinary Cancer 11/2013; · 1.43 Impact Factor
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    ABSTRACT: Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy.
    The Journal of clinical investigation 10/2013; 123(10):4344-4358. · 15.39 Impact Factor
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    ABSTRACT: In this prospective study of localized prostate cancer patients and their partners, we analyzed how partner issues evolve over time, focusing on satisfaction with care, influence of cancer treatment, and its impact on relationship with patient, cancer worry, and personal activities. Our study aims were twofold: (i) to determine whether the impact of treatment on patients and partners moderate over time and (ii) if receiving surgery (i.e., radical prostatectomy) influences partner issues more than other treatments. Patients newly diagnosed with localized prostate cancer and their female partners were recruited from three states to complete surveys by mail at three time points over 12 months. The four primary outcomes assessed in the partner analysis included satisfaction with treatment, cancer worry, and the influence of cancer and its treatment on their relationship (both general relationship and sexual relationship). This analysis included 88 patient-partner pairs. At 6 months, partners reported that cancer had a negative impact on their sexual relationship (39%-somewhat negative and 12%-very negative). At 12 months, this proportion increased substantially (42%-somewhat negative and 29%-very negative). Partners were significantly more likely to report that their sexual relationship was worse when the patient reported having surgery (P = 0.0045, odds ratio = 9.8025, 95% confidence interval 2.076-46.296). A minority of partners reported significant negative impacts in other areas involving their personal activities (16% at 6 months and 25% at 12 months) or work life (6% at 6 months, which increased to 12% at 12 months). From partners' perspectives, prostate cancer therapy has negative impact on sexual relationships and appears to worsen over time. Ramsey SD, Zeliadt SB, Blough DK, Moinpour CM, Hall IJ, Smith JL, Ekwueme DU, Fedorenko CR, Fairweather ME, Koepl LM, Thompson IM, Keane TE, and Penson DF. Impact of prostate cancer on sexual relationships: A longitudinal perspective on intimate partners' experiences. J Sex Med **;**:**-**.
    Journal of Sexual Medicine 09/2013; · 3.51 Impact Factor
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    ABSTRACT: Informal care plays an important role in the overall care for people with cancer. This study estimates lost productivity and informal caregiving and associated costs among partner caregivers of localized prostate cancer patients within 1 year after diagnosis. We applied data from the Family and Cancer Therapy Selection study, a three-wave self-administered survey among patients diagnosed with localized prostate cancer and their partner caregivers in multiple clinics in the USA. Time spent was measured by the sum of working hours lost, informal caregiving hours performed, and hours spent on household chores. The national median income for women 55 years or older was used to calculate costs associated with the time spent using the opportunity cost method. Descriptive and bivariate analyses were conducted. The average working hours decreased from 14.0 h/week (SD = 17.6) to 10.9 h/week (SD = 15.9), without a significant change in responsibility/intensity at work. The mean annual time spent on informal caregiving and household chores was 65.9 h/year (SD = 172.4) and 76.2 h/year (SD = 193.3), respectively. The mean annual economic burden among partner caregivers was US$6,063 (range US$571-US$47,105) in 2009 dollars accounted for by a mean of 276.2 h (range 26-2,146) in the study sample. The time spent on informal caregiving and household chores varied by patient and caregiver characteristics. Pilot estimates on non-medical economic burden among partner caregivers (spouses) during the initial phase of the treatment provide important information for comprehensive estimation of disease burden and can be used in cost-effectiveness analyses of prostate cancer interventions.
    Supportive Care in Cancer 08/2013; · 2.09 Impact Factor
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    ABSTRACT: PURPOSE: To preliminarily evaluate the potential for an improvement in diagnostic performance by a combined interpretation of In-111 capromab pendetide single photon emission computed tomography (SPECT) including computed tomography (CT) image fusion with magnetic resonance diffusion-weighted imaging (MR-DWI) for identifying prostate cancer in pelvic lymph nodes thru correlation with histopathology. MATERIALS AND METHODS: This institutional approved, retrospective study identified patients with available histopathology of lymph nodes removed at the time of radical prostatectomy and who had undergone staging with In-111 capromab pendetide SPECT-CT and/or pelvic MRI (including DWI). The performance of In-111 capromab pendetide SPECT for identifying malignant lymph nodes was assessed. Subsequently, a combined reading of In-111 capromab pendetide SPECT and prostate MRI with DWI was performed and the performance assessed. RESULTS: 18 patients underwent In-111 capromab pendetide SPECT-CT. Of these, 12 patients had also undergone imaging with MR-DWI. In-111 capromab pendetide SPECT-CT had a sensitivity of 40.0 % and specificity of 96.7 % for identification of malignant lymph nodes. However, In-111 capromab pendetide SPECT-CT combined with MRI with DWI had a sensitivity of 88.9 % and specificity of 98.5 %. CONCLUSIONS: The addition of MR-DWI to the interpretation of In-111 capromab pendetide SPECT-CT may increase the sensitivity for detecting malignant lymph nodes in prostate cancer. Future prospective evaluation of combined In-111 capromab pendetide SPECT-CT and MR-DWI is indicated and may improve clinical evaluation of nodal disease in prostate cancer.
    World Journal of Urology 04/2013; · 2.89 Impact Factor
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    ABSTRACT: BACKGROUND:: The objectives of the current study were to evaluate the safety and efficacy of gemcitabine and irinotecan (Irinogem) in patients with metastatic bladder cancer. Irinotecan and gemcitabine are newer-generation chemotherapeutic agents with different mechanisms of action, nonoverlapping toxicity profiles, and synergistic activity in vitro. METHODS:: Sixteen patients have been enrolled, of which 13 are evaluable for response. The median age is 68.5 years (range, 52 to 82 y). According to the Bajorin prognostic model for metastatic bladder cancer, 8 patients were classified as "low risk" and 8 as "intermediate risk." Gemcitabine 1000 mg/m and irinotecan 100 mg/m were administered on days 1 and 8 of each 3-week cycle. All patients had histologically proven transitional cell cancer of the bladder with bidimensionally measurable disease. All but 2 patients were chemotherapy naive at enrollment. RESULTS:: The median number of cycles administered was 4. Among the 13 patients evaluable for efficacy, objective radiographic response was documented in 8 patients (2 complete and 6 partial responses), 4 had stable disease, and 1 progressed on therapy. Median progression-free survival was 8.78 months (95% confidence interval, 5.98-15.38) and median overall survival was 13.51 months (95% confidence interval, 8.02-21.93). Toxicity evaluated in all 16 patients was modest: 2 episodes of febrile neutropenia, grades 3 to 4 neutropenia in 4 patients, grades 3 to 4 diarrhea in 2 patients, grades 3 to 4 fatigue in 1 patient, grades 3 to 4 nausea/vomiting in 2 patients, grades 3 to 4 neurological toxicity in 1 patient, and no grades 3 to 4 thrombocytopenia. No toxic deaths were noted. One patient discontinued therapy due to grade 4 fatigue, 1 due to stroke, 1 due to grade 4 colitis, 1 due to progressive disease, and 1 declined to participate in the trial after receiving the first cycle of therapy. CONCLUSIONS:: The results of the current study suggested that the combination of Irinogem was an effective treatment for patients with metastatic bladder cancer, with manageable toxicities. The study was closed early due to delays in accrual and loss of funding. Hence, the study lacks adequate power to make definite conclusions. Further studies in multi-institutional setting in patients with normal and compromised renal function are warranted.
    American journal of clinical oncology 12/2012; · 2.21 Impact Factor
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    ABSTRACT: To explore an alternative approach to quantifying the burden of side effects at 1 year after treatment for prostate cancer among both patients and their partners. We analyzed data from 75 couples in the Family and Cancer Therapy Selection study. Paired patients and family members were independently asked about their willingness to pay (WTP) for a hypothetical new treatment that cures prostate cancer without side effects if they could reconsider their treatment decision by indicating the maximum amount they would be willing to pay given 11 separate "bids" ranging from $0 to $1500 per month. Descriptive and regression analyses were conducted for patients and family members controlling for sociodemographic characteristics and health status; Spearman correlations were also examined. Among 75 couples analyzed, the income-adjusted mean WTP estimates per month were $400.8 (standard error [SE] $54.3) for patients and $650.2 (SE 72.2) for family members. The WTP between patients and family members was correlated (Pearson ρ 0.30; P = 0.01). After adjusting for covariates, the adjusted mean WTP per month was $588.1 (SE 65.77) for patients and $819.4 (SE 74.33) for family members. Wanting to avoid side effects at baseline predicted higher WTP for patients (P = 0.010). Experiencing sexual side effects was predictive of higher WTP for family members (P = 0.047). Fairly high WTP amounts for a hypothetical treatment without side effects suggests that patients and their partners are experiencing important burdens 1 year after treatment. The higher amounts partners are willing to pay and the correlation with sexual side effects suggest that they are perceptive of significant treatment burdens.
    Value in Health 07/2012; 15(5):716-23. · 2.19 Impact Factor
  • Urology 05/2012; 80(1):168. · 2.42 Impact Factor
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    ABSTRACT: We wanted to investigate vitamin D in low-risk prostate cancer. The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression. In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy. All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC. All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives. The intervention included vitamin D(3) soft gels (4000 IU). Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation. No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score. Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.
    The Journal of clinical endocrinology and metabolism 04/2012; 97(7):2315-24. · 6.50 Impact Factor
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    ABSTRACT: What's known on the subject? and What does the study add? Penile cancer is a rare malignancy with limited evidence to support most treatment recommendations. No randomised controlled trials have been published and few recommendations are available for guiding management. However, evidence‐based guidelines are currently available through the European Association of Urology.This review provides the reader with the most up‐to‐date information on diagnosis and management of all stages of squamous cell carcinoma of the penis. It provides a rapid review and study guide for this rare disease.• To review the current literature available on squamous cell carcinoma (SCC) of the penis and provide a contemporary management algorithm for treatment based on the best evidence available. • A complete review of the current English language literature was performed via PubMed and all available guidelines were reviewed. • Large randomised controlled trials are lacking in penile SCC due to the fortunately rare occurrence of the disease. • Treatment recommendations for the primary lesion, lymph nodes, and follow‐up in this review are based on the best current available literature. • Early diagnosis and aggressive organ‐sparing treatment remains the mainstay of therapy for penile SCC. • Variable institutional expertise currently makes treatment decisions difficult and unstandardised. • A multidisciplinary approach should be used in attempt to improve outcomes in this mutilating disease.
    BJU International 11/2011; 108(9):1378-92. · 3.05 Impact Factor
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    ABSTRACT: To determine the diagnostic performance of In-111 capromab pendetide single photon emission computed tomography/computed tomography (SPECT/CT), in the prostate gland, seminal vesicles, and lymph nodes via correlation to a gold standard of histopathology. In this study, we retrospectively reviewed all In-111 capromab pendetide SPECT/CT acquired at our institution for dedicated histopathology within a 4-month period. Statistical measures of performance were calculated in terms of glandular, seminal vesicle, and lymph node activity. The accuracies of glandular and seminal vesicle activity were then correlated to the indices of risk, including the stage, Gleason score, and prostate-specific antigen level, as well as the treatment history. Of the 200 scans meeting the criteria of our study, 197 had prostate gland histopathology, 94 had bilateral seminal vesicle histopathology, and 5 had a total of 43 resected lymph nodes for comparison. The overall accuracies of the scan results were determined to be 77.7% (area under the receiver operating characteristic curve [AUC] = 0.539) for the gland, 67.0% (AUC = 0.510) for the seminal vesicles, and 93.0% (AUC = 0.787) for lymph nodes. For glandular activity alone, scan accuracy was found to significantly improve with increasing Gleason score (P < 0.0001), and in a setting prior to treatment (P = 0.0005). No statistically significant differences were found between different scan groups with regards to seminal vesicle activity. The results of this study provide substantiating evidence In-111 capromab pendetide can be used to accurately diagnose lymph node metastases from primary cancers of the prostate; however, they also suggest the test may have limited utility in diagnosing tumors within the prostate gland and seminal vesicles.
    Clinical nuclear medicine 10/2011; 36(10):872-8. · 3.92 Impact Factor
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    ABSTRACT: Our study aims at understanding the timing and nature of mitochondrial deoxyribonucleic acid (mtDNA) alterations in urothelial cell carcinoma (UCC) and their detection in urine sediments. The entire 16.5 kb mitochondrial genome was sequenced in matched normal lymphocytes, tumor and urine sediments from 31 UCC patients and compared to different clinical stages and histological grades. The mtDNA content index was examined in all the specimens. Sixty-five percent (20/31) of the patients harbored at least 1 somatic mtDNA mutation. A total of 25 somatic mtDNA mutations were detected, which were more frequent in the respiratory complex coding regions (Complex I, III, IV and V) of the mtDNA and significantly affected respiratory Complex III compared to the other complexes (p = 0.021-0.039). Compared to Stage Ta, mtDNA mutation was higher in Stage T1 and significantly higher in Stage T2 (p = 0.01) patients. MtDNA mutation was also significantly higher (p = 0.04) in Stage T2 compared to Stage T1 patients. Ninety percent (18/20) of the patients harboring mtDNA mutation in the tumor also had mutation in their urine sediments. Eighty percent (20/25) of the tumor-associated mtDNA mutations was detectable in the urine sediments. Compared to the normal lymphocytes, the mtDNA content increased significantly in the tumor (p = 0.0013) and corresponding urine sediments (p = 0.0025) in 19/25 (76%) patients analyzed. Our results indicate that mtDNA alterations occur frequently in progressive stages of UCC patients and are readily detectable in the urine sediments. MtDNA mutations appear to provide a promising tool for developing early detection and monitoring strategies for UCC patients.
    International Journal of Cancer 08/2011; 131(1):158-64. · 6.20 Impact Factor
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    ABSTRACT: Acid ceramidase (AC) overexpression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC overexpression is the ability to convert ceramide, which is often produced as a proapoptotic response to stress, to sphingosine, which can then be converted to the prosurvival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines overexpressing AC also have increased lysosomal density and increased levels of autophagy. Furthermore, pretreatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6) ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that AC overexpression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide.
    Prostate cancer and prostatic diseases 03/2011; 14(1):30-7. · 2.10 Impact Factor
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    ABSTRACT: Penile cancer is rare, often presenting in later stages. We sought to determine if factors potentially related to access to care were associated with worse outcomes. We performed a retrospective review of all patients with the diagnosis of penile cancer over a 14 year period at the only tertiary referral center in the state. We collected data on multiple factors potentially associated with access to care. Fifty-five patients with penile cancer were identified. The average age was 57 years. Of the 55 patients, 23 patients (42%) had private insurance carriers, 16 (29%) had Medicare/Medicaid, 13 (24%) had no insurance, one had VA benefits, and no data was available on two patients. Typically, 4% of patients seen at our institution are uninsured. Pathologic tumor stage distribution was Tis (n = 9), Ta (1), T1 (15), T2 (16), and T3 (4). Nodal disease was present in 11, four of whom (38%) were uninsured, and metastatic disease was present in three. Of the 55 patients, eight admitted to greater than two alcoholic drinks per day three, of whom 38% presented with advanced disease. School district graduation rate was also calculated and similar among all groups. Univariate and multivariate modeling revealed no factors associated with delay to care. Patients presenting to a referral center in the southeastern United States with penile cancer more commonly lack health insurance. Additionally, patients who are heavy alcohol users or are uninsured present with advanced disease. These factors contribute to poorer prognosis in these patients.
    The Canadian Journal of Urology 02/2011; 18(1):5524-8. · 0.74 Impact Factor
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    ABSTRACT: • To evaluate the degree to which the partners of prostate cancer patients participate in the shared decision-making process with the patients' providers during the time between diagnosis and initiating treatment. • We recruited patients with newly diagnosed local-stage prostate cancer and their partners to complete take-home surveys after biopsy but before initiating treatment at urology practices in three states. • We asked partners to describe their roles in the decision-making process, including participation in clinic visits, and perceptions of encouragement from providers to participate in the treatment decision-making process. We also asked partners to rate their satisfaction with the patients' providers. • Family members of 80% of newly diagnosed patients agreed to participate; most (93%) were partners (i.e. spouses or significant others). Most partners (93%) had direct contact with the patients' physicians. • Among the partners who had contact with providers, most (67%) were very satisfied with the patients' providers and 80% indicated that the doctor encouraged them to participate in the treatment decision. Overall, 91% of partners reported very frequent discussions with their loved one about the pending treatment decision, and 69% reported that their role was to help the patient make a decision. • In multivariate models, provider encouragement of partner participation was associated with higher partner satisfaction (odds ratio 3.4, 95% CI 1.4-8.4) and an increased likelihood of partners reporting very frequent discussions with their loved one (odds ratio 6.1, 95% CI 1.3-27.7). • Partners often attended clinic visits and were very involved in discussions about treatment options with both loved ones and providers. • Provider encouragement of participation by partners greatly facilitates shared decision-making between patients and partners.
    BJU International 01/2011; 108(6):851-6; discussion 856-7. · 3.05 Impact Factor
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    ABSTRACT: Prostate cancer is the most commonly diagnosed cancer among American men. The multiple treatment options for localized prostate cancer and potential side effects can complicate the decision-making process. We describe the level of engagement and communication among the patient, family member, and physician (the decision-making "triad") in the decision process prior to treatment. Using the Family and Cancer Therapy Selection (FACTS) study baseline survey data, we note racial/ethnic variations in communication among the triad. Sensitivity to and awareness of decision-making styles of both the patient and their family member (or caregiver) may enable clinicians to positively influence communication exchanges about important clinical decisions.
    International Journal of General Medicine 01/2011; 4:481-6.

Publication Stats

708 Citations
199.41 Total Impact Points

Institutions

  • 2004–2014
    • Medical University of South Carolina
      • • Department of Microbiology and Immunology (College of Medicine)
      • • Department of Urology
      Charleston, South Carolina, United States
    • George Washington University
      Washington, Washington, D.C., United States
  • 2011–2013
    • Centers for Disease Control and Prevention
      • • Division Of Cancer Prevention and Control
      • • National Center for Chronic Disease Prevention and Health Promotion
      Atlanta, MI, United States
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
  • 2010
    • VA Puget Sound Health Care System
      Washington, Washington, D.C., United States
  • 2006
    • Walter Reed National Military Medical Center
      Washington, Washington, D.C., United States