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Peter R Carroll

Publications and source records attributed to Peter R Carroll.

At least 55 records · Page 3Linked to original sources
PubMed2005

Who is the average patient presenting with prostate cancer?

Prostate cancer screening, diagnosis, and treatment have changed dramatically in the last 20 years. Patients with newly diagnosed prostate cancer have many treatment options available. We attempted to determine how patient demographics and quality of life (QOL) have changed, and we describe the average patient with newly diagnosed prostate cancer in the early 21st century. From the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) we identified 3003 men with prostate cancer diagnosed between 1997 and 2003 for whom pretreatment demographic and QOL data were available. All patients completed both the University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) and the Rand Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) as self-administered questionnaires at the time of diagnosis. We compared demographic variables (age at diagnosis, race/ethnicity, education, number of comorbidities, body mass index [BMI], and insurance type), treatment choice, and pretreatment QOL scores on the SF-36 and UCLA-PCI scales for the periods 1997 to 1999 or 2000 to 2003. Stratified analysis by risk category was performed for demographic and QOL data for the 2 periods. Race/ethnicity and insurance demographics were statistically different for the 2 periods. Low-risk patients also showed a statistically increased BMI in the 2000 to 2003 period. Risk category predicted performance on both inventories, with low-risk patients having better function than intermediate-risk patients and high-risk patients in the areas of urinary bother, bowel function and bother, and sexual function and bother, as well as in many general well-being and emotional health scales on the SF-36. We conclude that the "average" prostate cancer patient is white, 65 years of age, overweight, educated at a college level, and has 1 to 2 comorbidities. Patients report average or above-average pretreatment health-related QOL for all scales based on 2 validated instruments. In this cohort, more patients chose radical prostatectomy than any other form of treatment.

Aged↗
PubMed2005

Obesity and prostate cancer clinical risk factors at presentation: data from CaPSURE.

PURPOSE: We investigated the association of obesity with prostate cancer case demographics and clinical disease features at presentation. MATERIALS AND METHODS: Data were abstracted from CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor), a disease registry of 10,018 men with prostate cancer. A total of 2,952 men were included who were treated between 1989 and 2002, and had complete body mass index (BMI) information. BMI classes were defined as normal (less than 25 kg/m), overweight (25 to 29.9 kg/m), obese (30 to 34.9 kg/m) or very obese (35 kg/m or greater). Patients were categorized as having low, intermediate or high risk disease based on the D'Amico classification. Associations among BMI, risk and demographics were analyzed using univariate and multivariate models. RESULTS: Of the patients 29% had a normal BMI, 51% were overweight, 16% were obese and 5% were very obese. Patients who were overweight or obese were more likely to be young, have hypertension and diabetes, and have a lower education level. The overweight group had a lower serum prostate specific antigen (p = 0.010) and lower stage disease (p = 0.030) at diagnosis, but there was no association between Gleason score and obesity (p = 0.57). However, among men with a BMI of 25 kg/m or greater there was a positive correlation between increasing BMI and risk of being in a worse prognostic group at diagnosis (p = 0.018). CONCLUSIONS: Overweight and obese patients are more likely to be young at diagnosis and have multiple comorbidities. Men in the overweight and obese groups presented with lower risk prostate cancer at diagnosis. This may be due to earlier disease detection secondary to more frequent interaction with the medical community. Among overweight and obese patients increased obesity is associated with a slightly increased chance of having high risk prostate cancer at diagnosis.

Adenocarcinoma↗
PubMed2005

Treatment of patients with high risk localized prostate cancer: results from cancer of the prostate strategic urological research endeavor (CaPSURE).

PURPOSE: Pretreatment risk assessment models facilitate more appropriate selection of treatment for prostate cancer. However, men with high risk disease remain a challenge with significant potential for primary treatment failure. We characterize patterns of treatment for high risk prostate cancer in a community based cohort. MATERIALS AND METHODS: In the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, a longitudinal disease registry of men with prostate cancer, we identified those with nonmetastatic, high risk disease based on T stage, tumor grade and serum prostate specific antigen (PSA). Differences in primary treatment, and the use of neoadjuvant and adjuvant therapy in patients at low, intermediate and high risk were assessed. In the high risk cohort predictors of the type of primary treatment, and the use of neoadjuvant and adjuvant androgen therapy were identified. RESULTS: Of the cancers 34%, 40% and 26% were low, intermediate and high risk, respectively. Differences in primary treatment type among the 3 risk groups were statistically significant (p <0.0001) with increasing external beam radiation therapy and androgen deprivation, and decreased surgery, brachytherapy and surveillance in men with high risk cancers. In this group older age, higher PSA and nonprivate insurance were associated with decreased use of radical prostatectomy. More than half of the men at high risk receiving radiation therapy also received androgen deprivation, which was significantly higher than in the low and intermediate risk groups (p <0.0001). Factors associated with androgen deprivation in high risk disease were primary therapy, PSA, Gleason sum, T stage, body mass index, insurance status and ethnicity. PSA and Gleason sum were the primary determinants of adjuvant radiation after prostatectomy. CONCLUSIONS: Men with high risk but nonmetastatic prostate cancer are more likely to receive radiation therapy as well as androgen deprivation with the latter as primary therapy or in conjunction with local treatment. These data stress the importance of pretreatment risk stratification, education regarding appropriate combinations of local and systemic therapies, and the consideration of novel clinical trials in patients at higher risk.

Aged↗
PubMed2005

The impact of obesity on health related quality of life before and after radical prostatectomy (data from CaPSURE).

PURPOSE: Health related quality of life (HRQOL) is an important measure of outcomes among patients with prostate cancer due to disease related and treatment related effects on physical and emotional health. We determined if there are differences in the HRQOL of obese men at diagnosis and after radical prostatectomy compared to the HRQOL of men with normal body mass index (BMI). MATERIALS AND METHODS: Data were abstracted from Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE), a disease registry of 10,018 men with prostate cancer. A total of 1,884 men were included in study who were treated with radical prostatectomy between 1989 and 2002, had BMI information available and had completed 1 initial HRQOL questionnaire. Of these men 672 who completed at least 2 followup questionnaires were assessed further. RESULTS: The BMI (kg/m) distributions were 24% normal (less than 24.9 kg/m), 56% overweight (25 to 29.9), 16% obese (30 to 34.9) and 4% very obese (greater than 35 kg/m). Higher BMI was associated with worse physical function, bodily pain, general health, vitality and role physical, but better bowel bother at diagnosis independent of race. Higher BMI was also associated with worse HRQOL after radical prostatectomy for physical function, general health and vitality, but better bowel bother. HRQOL differences between BMI groups were similar among times for all measured variables. Compared to the normal group, the higher BMI groups had similar HRQOL after radical prostatectomy. CONCLUSIONS: In the majority of domains men with higher BMI had lower HRQOL at diagnosis than men of normal BMI. Obese men have a similar recovery pattern of HRQOL after radical prostatectomy, with minimal additive long-term impairment in HRQOL relative to men of normal weight.

Activities of Daily Living↗
PubMed2005

Ability of 2 pretreatment risk assessment methods to predict prostate cancer recurrence after radical prostatectomy: data from CaPSURE.

PURPOSE: Two methods widely used to predict the risk of treatment failure after radical prostatectomy for localized prostate cancer are the 3 level D'Amico risk classification and the Kattan nomogram. Although they have been previously validated, to our knowledge they have not been compared in a community based cohort. We tested the 2 instruments in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, a national registry of patients with prostate cancer, to assess their accuracy in a community based cohort. MATERIALS AND METHODS: Men were invited to join CaPSURE from 33 American urology practices, of which 30 were community based. A total of 1,701 men with localized prostate cancer (T1-3a) were treated with radical prostatectomy between 1989 and 2000. Patients who received neoadjuvant or adjuvant therapy were excluded. Recurrence was defined as 2 or more consecutive prostate specific antigen measurements of 0.2 ng/ml or greater, or a second treatment greater than 6 months after surgery. Freedom from progression (FFP) was based on life table estimates and Kaplan-Meier curves. Risk groups were compared using a Cox proportional hazards model and ANOVA. RESULTS: Based on the D'Amico classification 671 cases (39%) were classified as low risk, 446 (26%) were intermediate risk and 584 (34%) were high risk. Five-year FFP was 78%, 63% and 60% in the low, intermediate and high risk groups (HR 1.00, 1.87 and 2.32 respectively, p <0.0001). Mean 5-year FFP predicted by the Kattan nomogram in the same risk groups was 91%, 74% and 69%, respectively. Outcomes in the low risk group were tightly grouped about the mean but there was considerable dispersion of outcomes in the intermediate (30% to 98% FFP) and high (17% to 98%) risk groups. CONCLUSIONS: Stratifying patients in CaPSURE into low, intermediate and high risk categories for disease as described by D'Amico or applying the Kattan nomogram resulted in statistically significant differences in predicted 5-year FFP. However, there was considerable overlap of outcomes between the intermediate and high risk groups. This analysis suggests that simply estimating disease recurrence by stratifying patients into low, intermediate and high risk groups may not provide sufficient information for predicting outcomes among individuals.

Adult↗
PubMed2005

Surrogate end point for prostate cancer specific mortality in patients with nonmetastatic hormone refractory prostate cancer.

PURPOSE: We determined whether prostate specific antigen (PSA) velocity can serve as surrogate end point for prostate cancer specific mortality (PCSM) in patients with nonmetastatic, hormone refractory prostate cancer. MATERIALS AND METHODS: The study cohort comprised 919 men treated from 1988 to 2002 at 1 of 44 institutions with surgery (560) or radiation therapy (359) for clinical stages T1c-4NxMo prostate cancer, followed by salvage hormonal therapy for PSA failure. All patients experienced PSA defined recurrence while on hormonal therapy. Prentice criteria require that the surrogate should be a prognostic factor and the treatment used did not alter time to PCSM following achievement of the surrogate end point. These criteria were tested using Cox regression. All statistical tests were 2-sided. RESULTS: PSA velocity greater than 1.5 ng/ml yearly was statistically significantly associated with time to PCSM and all cause mortality following PSA defined recurrence while undergoing hormonal therapy (Cox p <0.0001). While initial treatment was statistically associated with time to PCSM and all cause mortality (Cox p = 0.001 and 0.01), this association became insignificant when PSA velocity and potential confounding variables were included in the Cox model (p = 0.22 and 0.93, respectively). The adjusted HR for PCSM in patients who experienced a greater than 1.5 ng/ml increase in PSA within 1 year while on hormonal therapy was 239 (95% CI 10 to 5,549). CONCLUSIONS: These data provide evidence to support PSA velocity greater than 1.5 ng/ml yearly as a surrogate end point for PCSM in patients with nonmetastatic, hormone refractory prostate cancer. Enrolling these men onto clinical trials evaluating the impact of chemotherapy on time to bone metastases and PCSM is warranted.

Aged↗
PubMed2005

The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy.

PURPOSE: Multivariate prognostic instruments aim to predict risk of recurrence among patients with localized prostate cancer. We devised a novel risk assessment tool which would be a strong predictor of outcome across various levels of risk, and which could be easily applied and intuitively understood. MATERIALS AND METHODS: We studied 1,439 men diagnosed between 1992 and 2001 who had undergone radical prostatectomy and were followed in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, a longitudinal, community based disease registry of patients with prostate cancer. Disease recurrence was defined as prostate specific antigen (PSA) 0.2 ng/ml or greater on 2 consecutive occasions following prostatectomy or a second cancer treatment more than 6 months after surgery. The University of California, San Francisco-Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score was developed using preoperative PSA, Gleason score, clinical T stage, biopsy results and age. The index was developed and validated using Cox proportional hazards and life table analyses. RESULTS: A total of 210 patients (15%) had recurrence, 145 by PSA criteria and 65 by second treatment. Based on the results of the Cox analysis, points were assigned based on PSA (0 to 4 points), Gleason score (0 to 3), T stage (0 to 1), age (0 to 1) and percent of biopsy positive cores (0 to 1). The UCSF-CAPRA score range is 0 to 10, with roughly double the risk of recurrence for each 2-point increase in score. Recurrence-free survival at 5 years ranged from 85% for a UCSF-CAPRA score of 0 to 1 (95% CI 73%-92%) to 8% for a score of 7 to 10 (95% CI 0%-28%). The concordance index for the UCSF-CAPRA score was 0.66. CONCLUSIONS: The UCSF-CAPRA score is a straightforward yet powerful preoperative risk assessment tool. It must be externally validated in future studies.

Adenocarcinoma↗
PubMed2005

Update on chemotherapy for advanced bladder cancer.

PURPOSE: Recent years have seen several advances in the treatment of locally advanced and metastatic bladder cancer. We summarize the current state of the art for advanced bladder cancer treatment. MATERIALS AND METHODS: A comprehensive review of published, prospective phase II/III clinical trials and retrospective analyses of patients with advanced bladder cancer was performed. RESULTS: Adjuvant and neoadjuvant chemotherapeutic strategies around the time of radical cystectomy have been used to decrease the risk of subsequent metastatic disease. Although the benefit of adjuvant chemotherapy remains unproven, neoadjuvant chemotherapy is associated with a modest 5% to 6% absolute survival benefit in 2 meta-analyses of the available data. Chemoradiation is feasible and effective in some patients, allowing bladder preservation with an acceptable risk of progression. Randomized, phase III data comparing methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy to gemcitabine/cisplatin showed similar response proportions and overall survival with less toxicity in the gemcitabine/cisplatin arm. This has led to the widespread use of gemcitabine/cisplatin as first line chemotherapy for metastatic bladder cancer. The optimal agents and regimens for second line chemotherapy remain undefined. Similarly biological and targeted therapies for advanced bladder cancer remain investigational. CONCLUSIONS: Combination cisplatin based neoadjuvant chemotherapy may benefit patients with locally advanced bladder cancer. Gemcitabine/cisplatin has replaced methotrexate, vinblastine, doxorubicin and cisplatin as the regimen of choice in patients with good renal function. The optimal regimens for the medically unfit patient and second line chemotherapy remain undefined. The development of targeted therapies, less toxic regimens and improved cytotoxic agents are necessary to improve outcomes.

Carcinoma, Transitional Cell↗
PubMed2005

Management of isolated renal fossa recurrence following radical nephrectomy.

PURPOSE: Local recurrence of renal cell carcinoma in the renal fossa without distant metastatic disease is an infrequent occurrence. Management of this lesion can be challenging, with relatively few series in the literature. We describe our use of surgical extirpation with adjuvant intraoperative radiation. MATERIALS AND METHODS: The University of California, San Francisco Urologic Oncology database and the University of California, San Francisco Radiation Oncology database were queried for all patients with locally recurrent renal fossa recurrence. Only patients with recurrence of renal cell carcinoma in the renal fossa were included. Survival, complications and the use of adjuvant therapy in the form of intraoperative radiation therapy were noted. RESULTS: A total of 14 patients were treated for this lesion between 1990 and 2003. Mean time to recurrence was 40 months (range 5 to 180). Only 1 patient was symptomatic preoperatively, while in 13 disease had been detected on routine computerized tomography followup. Mean size of the recurrent tumor was 6.35 cm (range 2 to 17). 9 patients died of progressive, metastatic disease after a mean of 17 months (range 1 to 56) and 5 are alive with a mean survival of 66 months (range 14 to 86). The time to recurrence after nephrectomy approached statistical significance (p =0.06) when comparing the patients who were alive vs those who died of disease. Additionally, there was no statistical difference in size of mass recurrence between these 2 groups. There was no difference in survival due to adjuvant intraoperative radiation therapy. Local fossa re-recurrence developed in 2 patients. Survival was 40% at 2 years and 30% at 5 years from surgery. Complications, including minor complications, occurred in 42% of patients and there was no perioperative mortality. CONCLUSIONS: Selected patients with isolated local recurrence in the renal fossa may have favorable and durable outcomes following surgical resection and possibly adjuvant intraoperative radiation therapy for isolated renal fossa recurrence following radical nephrectomy. Development of novel and effective systemic therapy is needed in high risk patients with renal cancer.

Adolescent↗
PubMed2005

Intensive lifestyle changes may affect the progression of prostate cancer.

PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.

Aged↗
PubMed2005

Androgen deprivation use with external beam radiation for prostate cancer: results from CaPSURE.

PURPOSE: Recent data support the role of androgen deprivation in men undergoing external beam radiotherapy for prostate cancer. The benefits of neoadjuvant, concurrent or adjuvant treatment have been limited to men at intermediate and high risk. We examined the patterns and predictors of androgen deprivation in men undergoing external beam radiation therapy in CaPSURE. MATERIALS AND METHODS: CaPSURE is an observational, longitudinal disease registry, from which 932 men met study inclusion criteria. Androgen deprivation was classified as neoadjuvant-within 9 months of radiation or adjuvant-from the start of radiation to 6 months after completion. Time trends in androgen deprivation as well factors associated with combined therapy were elucidated using multivariate analyses. RESULTS: In this study 40%, 39% and 21% of men could be categorized into high, intermediate and low risk groups, respectively. Overall 42% and 33% of patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. Between 1997 and 2002 neoadjuvant hormone use increased significantly in all risk groups, including patients at low risk. On multivariate analyses only the year of diagnosis and clinical risk group were associated with receiving androgen deprivation with radiation. CONCLUSIONS: A significant increase in combined androgen deprivation and external radiation was observed in the last decade in men with intermediate and high risk disease. Nevertheless, more widespread acceptance is necessary since a substantial minority continue to receive radiation alone. Many patients with low risk disease that is amenable to radiation monotherapy also receive androgen deprivation. No clinical or sociodemographic features predicted the use of androgen deprivation with external radiation.

Adenocarcinoma↗
PubMed2005

The independent impact of extended pattern biopsy on prostate cancer stage migration.

PURPOSE: There are many factors impacting stage migration for prostate cancer. The number of prostate core biopsies is known to increase detection of prostate cancers. It is still unknown whether the number of biopsies is an independent predictor of tumor size. This is important as a number of studies show that tumor volume is an independent predictor of cancer progression. MATERIALS AND METHODS: Using the University of California, San Francisco Urologic Oncology database, a retrospective review of 378 patients undergoing radical prostatectomy by a single surgeon during 2000 to 2003 was performed. Patient and tumor specific variables including age, prostate specific antigen (PSA), number of biopsies, biopsy Gleason grade, tumor volume in the surgical specimen and surgical specimen tumor grade were studied. Univariate and multivariate statistical methods including multiple and logistic regression were used to characterize patients by the number of biopsy cores. Tests of significance to identify predictors of tumor size were based on the partial F statistic and the likelihood ratio test. RESULTS: A total of 317 eligible patients were studied, of whom 119 had 6 biopsies and 198 had more than 6 biopsies. The 2 groups of patients were evenly matched in terms of age, PSA and Gleason sum, with no statistically significant differences observed. On univariate analysis, mean tumor volume was larger for patients receiving 6 core biopsies vs greater than 6 core biopsies (3.85 vs 2.04 cc, p = 0.0009). Additionally, statistically significant differences were observed when comparing median tumor volumes, as well as excluding extremely large volume tumors. On multivariate analysis the number of biopsies performed (6 vs more than 6), was an independent predictor of tumor size (p = 0.006), controlling for primary Gleason score, Gleason sum, PSA as a continuous or categorical variable, year of biopsy and year of surgery. CONCLUSIONS: The use of extended pattern prostate biopsy templates results in the detection of smaller volume prostate cancers, independent of PSA and Gleason grade. These biopsy templates have contributed to the downward stage migration of prostate cancer detection and may possibly contribute to the risk of over detection.

Adult↗
PubMed2005

Lifestyle correlates of health perception and treatment satisfaction in a clinical cohort of men with prostate cancer.

There is a growing need to understand how nutritional and lifestyle practices may optimize quality of life (QOL) and health after diagnosis for the 1.5 million men living with prostate cancer in the United States. We are establishing a clinical cohort of men with prostate cancer at the University of California San Francisco. Men completed detailed dietary and lifestyle questionnaires annually and provided consent for blood and tissue specimens to be stored for research if they underwent radical prostatectomy. We examined the feasibility of establishing this cohort and analyzepreliminary baseline data on participant demographics, lifestyle habits, and QOL using c2 and t-tests and logistic regression models. Between February 2002 and July 2004, we enrolled 343 men with prostate cancer into the survey portion of this cohort. The response rate was approximately 85% via in-clinic enrollment and 30% via mail enrollment. Based on analysis of the first 193 men enrolled, there was a high level of treatment satisfaction in this population (88% of men were satisfied or extremely satisfied with treatment) and positive reports of general health perception (73% of men perceived themselves to be in excellent [34%] or very good [39%] health). Whether treatment interfered with diet was an independent predictor of health perception and treatment satisfaction. Use of dietary supplements was high (90%) in this well-educated population. In conclusion, we demonstrated good feasibility for conducting this longitudinal study and observed initial indications that diet and other lifestyle practices were important predictors of patient QOL.

Aged↗
PubMed2005

Demographics, insurance coverage, and utilization of medical services in newly diagnosed prostate cancer: data from caPSURE.

This study was conducted to identify factors that might influence access to medical services by patients with prostate cancer. The sample comprised 1882 patients who underwent radical prostatectomy and received at least six months of posttreatment follow-up. The investigators found that the type of insurance coverage significantly influenced the number of visits to general practitioners, mental health professionals, and oncologists. However, visits to urologists, nurse practitioners, or alternative-therapy providers were not influenced by type of insurance coverage. Moreover, race, risk profile, and education were significantly correlated with utilization of health services by these patients. The influence of demographic features and insurance coverage on health care utilization by patients with prostate cancer should be further explored.

Aged↗
PubMed2004

Inactivation of the hMSH3 mismatch repair gene in bladder cancer.

Deficiency in the DNA mismatch repair (MMR) is frequently involved in various cancers. The hMSH3 gene is one of the human MMR genes whose role in bladder cancer is not known. We hypothesized that down-regulation of the hMSH3 gene might be involved in bladder cancer. In this study we analyzed this gene with regard to frame-shift mutation, single nucleotide polymorphism (SNP), a 9bp repeat in exon 1, loss of heterozygosity (LOH), immunohistochemistry, and methylation status in 102 bladder cancer samples. Immunohistochemistry revealed that hMSH3 expression in bladder cancer was significant decreased compared to normal epithelium (p<0.0001). An inverse correlation with pathological grade was found. The frame-shift mutation in the (A) 8 tract was lacking in bladder cancer. There was no significantly difference between bladder cancer samples and healthy controls' with regard to SNP and the 9bp repeat. In bladder cancer, presence of the codon 222 polymorphism, LOH, and the 9bp repeats in exon 1 had a correlation with either pathological stage or pathological grade. Presence of the codon 1036 polymorphism had significant correlation with pathological stage and a trend to correlation with pathological grade. After 5-aza-dC treatment, MSH3 expression was significantly enhanced in TCC and UMUC bladder cancer cells when compared to untreated cells. This is the first report suggesting that genetic and epigenetic alterations in the human MSH3 gene might play a significant role in the progression of bladder tumors.

Azacitidine↗
PubMed2004

Longitudinal assessment of changes in sexual function and bother in patients treated with external beam radiotherapy or brachytherapy, with and without neoadjuvant androgen ablation: data from CaPSURE.

PURPOSE: To evaluate the effects of external beam radiotherapy (EBRT), with or without brachytherapy (BT) boost or brachytherapy monotherapy with and without short-term androgen ablation (<==6 months; STAD) on sexual function (SF) and sexual bother (SB) in men treated for localized prostate cancer. METHODS AND MATERIALS: A total of 992 men with newly diagnosed prostate cancer enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor database were studied to assess treatment-related changes in SF and SB. Six treatment subgroups (EBRT - STAD, EBRT + STAD, BT - STAD, BT + STAD, EBRT + BT - STAD, EBRT + BT + STAD) were compared. RESULTS: The greatest reported changes in SF occurred during the first 2 posttreatment years. Patients receiving BT reported greater SF and the least change in SF overall; those receiving EBRT + BT reported the greatest decline in SF. SF scores associated with STAD were initially lower than in patients without STAD; however by 1 year no statistically significant difference in SF or SB was noted. CONCLUSION: Each treatment for prostate cancer can negatively affect SF and SB. Initial differences among treatment subgroups exist, but diminish with time. SF changes associated with EBRT +/- BT were statistically significant and those for BT were not. STAD appeared to confer only temporary and recoverable impairment of erectile function.

Aged↗
PubMed2004

CpG hypermethylation of MDR1 gene contributes to the pathogenesis and progression of human prostate cancer.

Multidrug resistance 1 (MDR1) gene encodes for P-glycoprotein (P-gp), a Mr 170,000 transmembrane calcium-dependent efflux pump that is inactivated in prostate cancer. We hypothesize that inactivation of the MDR1 gene through CpG methylation contributes to the pathogenesis and progression of prostate cancer. To test this hypothesis, CpG methylation status of the MDR1 promoter and its correlation with clinicopathological findings were evaluated in 177 prostate cancer samples and 69 benign prostate hypertrophy (BPH) samples. Cellular proliferation index and apoptotic index were determined by proliferating cell nuclear antigen (PCNA) and single-strand DNA immunostaining, respectively. After 5-aza-2'-deoxycytidine treatment, increased expression of MDR1 mRNA transcript was found in prostate cancer cell lines (DU145, DuPro, and ND1). MDR1 methylation frequency was significantly higher in prostate cancer samples compared with BPH samples (54.8 versus 11.6%, respectively, P < 0.001). Logistic regression analysis revealed that PC patients are 11.5 times more likely to have MDR1 methylation than BPH patients (95% confidence interval 4.87-27.0) and that MDR1 methylation is independent of the age. Significant correlation of MDR1 methylation was observed with high pT category (P < 0.001), high Gleason sum (P = 0.008), high preoperative prostate-specific antigen (P = 0.01), and advancing pathological features. In addition, PCNA-labeling index were significantly higher in methylation-specific PCR (MSP)-positive than in MSP-negative prostate cancer samples (P = 0.048). In contrast, no significant difference in apoptotic index was found between MSP-positive and -negative prostate cancer samples. These findings suggest that CpG hypermethylation of MDR1 promoter is a frequent event in prostate cancer and is related to disease progression via increased cell proliferation in prostate cancer cells.

Aged↗