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Ganesh S Palapattu

Publications and source records attributed to Ganesh S Palapattu.

At least 19 recordsLinked to original sources
PubMed2026

Understanding randomized controlled trial generalizability through an embedded molecular diagnostics trial.

BACKGROUND: Issues with randomized controlled trial generalizability are well described, but whether these issues result from differences in patient treatment across contexts remains unknown. We studied treatment of patients with high-risk prostate cancer after radical prostatectomy inside and outside a randomized controlled trial evaluating the impact of a genomic classifier on post-radical prostatectomy treatment decision making (Genomics in Michigan Impacting Observation of Radiation [G-MINOR]; ClinicalTrials.gov identifier NCT02783950). METHODS: G-MINOR enrolled 338 patients; propensity score-matched eligible but unenrolled patient cohorts (pretrial and trial contemporary) from the Michigan Urological Surgery Improvement Collaborative (MUSIC), in which the trial was embedded, were compared for rates and time to secondary treatment (adjuvant or salvage therapy) after prostatectomy. RESULTS: Among 338 patients in the G-MINOR cohort, 69 (31 adjuvant, 38 salvage) received secondary treatment compared with 266 (183 adjuvant, 83 salvage) and 104 (60 adjuvant, 44 salvage) in the 1014 contemporary and 338 pretrial-matched MUSIC cohorts. Time to secondary treatment was much shorter in the MUSIC cohort across all comparisons. For example, matching G-MINOR to synchronous MUSIC patients demonstrated 84% vs 74% estimated 2-year treatment-free survival for trial and real-world patients, respectively (P&#x2009;<&#x2009;.001). CONCLUSIONS: Controlling for key clinicopathologic factors, patients in the G-MINOR randomized controlled trial and MUSIC cohorts were treated differently, even after stratifying by genomic risk. These findings suggest that challenges in randomized controlled trial generalizability extend beyond the representativeness of trial participants. Differences in management may also explain why divergent patient outcomes are observed in randomized controlled trials vs real-world settings.

Aged↗
PubMed2006

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.

Adult↗
PubMed2006

Advanced age is associated with poorer bladder cancer-specific survival in patients treated with radical cystectomy.

OBJECTIVE: Bladder cancer (BCa) is a disease of older persons, the incidence of which is expected to increase as the population ages. There is controversy, however, regarding the outcomes of radical cystectomy (RC), the gold standard treatment of high-risk BCa, in patients of advanced chronological age. The aim of our study was to assess the impact of patient age on pathological characteristics and recurrence-free and disease-specific survival following RC. METHODS: The records of 888 consecutive patients who underwent RC for transitional cell carcinoma (TCC) were reviewed. Age at RC was analyzed both as a continuous (yr) and categorical (< or =60 yr old, n=240; 60.1-70 yr old, n=331; 70.1-80 yr old, n=266; >80 yr old, n=51) variable. Logistic regression and survival analyses were performed. RESULTS: Higher age at RC, analyzed as a continuous or categorical variable, was associated with extravesical disease and pathological upstaging (all p<0.02). Older patients were less likely to receive postoperative chemotherapy (< or =60 yr: 32% vs. >80 yr: 14%, p=0.008). In both pre- and postoperative multivariate models, higher age at RC as a categorical variable was associated with BCa-specific survival (p<0.05). Patients >80 yr old had a significantly greater risk of disease recurrence than patients aged < or =60 yr (p<0.05). CONCLUSION: Greater patient age at the time of RC for BCa is independently associated with adverse outcomes. Better understanding of factors associated with postoperative outcomes in this growing segment of the population is necessary. Prospective corroboration and further refinement of similar analyses in other large datasets is needed.

Adult↗
PubMed2006

Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy.

OBJECTIVES: To describe the cancer-specific outcomes of patients with pathologic carcinoma in situ (CIS) only at radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder transitional cell carcinoma at three U.S. academic centers were reviewed. Of the 812 patients, 99 (12%) had CIS only at radical cystectomy. RESULTS: The distribution of clinical stage for the 99 patients with CIS only at radical cystectomy was as follows: 47% of patients had CIS only, 8% had cT1, 15% had cT1 plus CIS, 10% had cT2, 13% had cT2 plus CIS, 6% had cTa, and 1% had Ta plus CIS. Two patients had lymphovascular invasion in the radical cystectomy specimen, and three had metastases to the lymph nodes. The actuarial recurrence-free survival estimates were 89.8% (95% confidence interval [CI] 83.0% to 96.6%) at 3 years and 83.0% (95% CI 73.2% to 92.8%) at 5 and 7 years after radical cystectomy. Six patients (6%) had died of bladder cancer at analysis and 13 (13%) had died of other causes without evidence of disease recurrence. The actuarial disease-specific survival estimates were 95.8% (95% CI 91.2% to 99.9%) at 3 years, 90.7% (95% CI 82.4% to 98.9%) at 5 years, and 87.2% (95% CI 76.8% to 97.5%) at 7 years after surgery. On univariate Cox regression analyses, only metastasis to lymph nodes was associated with bladder cancer recurrence and death (P <0.001). CONCLUSIONS: Disease control seemed durable for patients with pathologic CIS only at radical cystectomy in the absence of metastases to the lymph nodes, even in the case of failure after intravesical therapy.

Adult↗
PubMed2006

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy.

OBJECTIVES: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses. RESULTS: Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features. CONCLUSIONS: Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.

Adult↗
PubMed2006

Precystectomy nomogram for prediction of advanced bladder cancer stage.

OBJECTIVE: To evaluate precystectomy prediction of pT and pN stages at cystectomy. METHODS: Multivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT(3-4) stage at cystectomy, and the second set predicted pN(1-3) stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias. RESULTS: At TUR, 11% of patients were staged as pT(3-4) versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN(1-3)). The multivariate pT(3-4) nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN(1-3) nomogram was 63.1% accurate versus 61.0% for TUR T stage. CONCLUSION: Multivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.

Adult↗
PubMed2006

Discrepancy between clinical and pathologic stage: impact on prognosis after radical cystectomy.

OBJECTIVES: We compared clinical and pathologic staging in a large, contemporary, consecutive series of patients who were treated with radical cystectomy and pelvic lymphadenectomy, and determined the effect of stage discrepancy on outcomes. METHODS: We collected retrospective data from 778 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy, and for whom the clinical and pathologic stage were available. RESULTS: Pathologic upstaging occurred in 42% of patients, and pathologic downstaging occurred in 22%. Forty percent of patients with non-muscle-invasive clinical stage had muscle-invasive pathologic stage. Thirty-six percent of patients with organ-confined clinical stage had non-organ-confined pathologic stage (> or =pT3N0 or pTanyN-positive). Patients with higher clinical stage were more likely to be upstaged to non-organ-confined disease (p<0.001). Patients were stratified into three groups: pathologically upstaged, same clinical and pathologic stage, and pathologically downstaged. When adjusted for the effects of standard postoperative features, upstaged patients were at a significantly higher risk of disease recurrence and bladder cancer-specific death than patients who had the same pathologic and clinical stage, who in turn were at significantly higher risk than downstaged patients. This observation remained true within each clinical stage strata. Within each pathologic stage strata, clinical stage did not substratify into different risk groups. CONCLUSIONS: Clinical to pathologic stage discrepancy is a relatively common finding after extirpative surgery for bladder cancer. Clinical outcomes after radical cystectomy are largely driven by pathologic stage. Better clinical staging is necessary to improve patient evaluation and management.

Adult↗
PubMed2006

Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

PURPOSE: Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. MATERIALS AND METHODS: Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. RESULTS: Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green fluorescent protein positive cells in the epithelial compartment 14 days after injury expressed cytokeratin 5/8, similar to the proportion of green fluorescent protein positive cells in the prostate that no longer expressed the hematopoietic marker CD45. When prostatic degeneration/regeneration was triggered by androgen deprivation and reintroduction, no green fluorescent protein positive prostate epithelial cells were detected. CONCLUSIONS: These findings are consistent with a requirement for inflammation associated architectural destruction for the bone marrow derived cell contribution to the regeneration of prostate epithelium.

Animals↗
PubMed2006

Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder.

PURPOSE: American Joint Committee on Cancer staging represents the gold standard for prediction of recurrence after radical cystectomy in patients with invasive bladder cancer. We tested the hypothesis that American Joint Committee on Cancer stage based predictions may be improved when pathological tumor and node stage information is combined with additional clinical and pathological variables within a prognostic nomogram. MATERIALS AND METHODS: We used Cox proportional hazards regression analysis to model variables of 728 patients with transitional cell carcinoma of the bladder treated with radical cystectomy and bilateral pelvic lymphadenectomy at 1 of 3 participating institutions. Standard predictors, pT and pN, were complemented by age, gender, tumor grade at cystectomy, presence of lymphovascular invasion, presence of carcinoma in situ in the cystectomy specimen, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy. The concordance index was used to quantify the accuracy of regression coefficient based nomograms. A total of 200 bootstrap resamples were used to reduce overfit bias and for internal validation. Calibration plots were used to graphically explore the performance characteristics of the multivariate nomogram. RESULTS: Followup ranged from 0.1 to 183.4 months (median 24.9, mean 36.4). Recurrence was recorded in 249 (34.2%) patients with a median time to recurrence of 108 months (range 0.8 to 131.9). Actuarial recurrence-free probabilities were 69.6% (95% CI 65.8%-73.0%), 60.2% (55.8%-64.3%) and 52.9% (47.3%-58.1%) at 2, 5 and 8 years after cystectomy, respectively. Two-hundred bootstrap corrected predictive accuracy of American Joint Committee on Cancer stage based predictions was 0.748. Accuracy increased by 3.2% (0.780) when age, lymphovascular invasion, carcinoma in situ, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy were added to pathological stage information and used within a nomogram. CONCLUSIONS: A nomogram predicting bladder cancer recurrence after cystectomy is 3.2% more accurate than American Joint Committee on Cancer stage based predictions. Moreover, a nomogram approach combines several advantages such as easy and precise estimation of individual recurrence probability at key points after cystectomy, which all patients deserve to know and all treating physicians need to know.

Adult↗
PubMed2006

Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium.

PURPOSE: We present the characteristics and outcomes of a large, contemporary, consecutive series of patients treated with radical cystectomy and pelvic lymphadenectomy for transitional cell carcinoma of the bladder. MATERIALS AND METHODS: We developed a multi-institutional database and collected retrospective and prospective data on 888 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy at 3 academic centers in the United States between 1984 and 2003. RESULTS: Of the patients 25% had extravesical tumor extension with negative lymph nodes and 23% had lymph node metastasis. The rate of lymph node involvement increased with advancing pathological stage. Mean recurrence-free and bladder cancer specific survival +/- SE was 58% +/- 2% and 66% +/- 2% at 5 years, respectively. On preoperative multivariate analysis clinical tumor stage and neoadjuvant systemic chemotherapy were associated with cancer recurrence, while more advanced age, clinical tumor stage and preoperative carcinoma in situ were associated with bladder cancer specific mortality. On postoperative multivariate analysis pathological tumor stage, lymph node metastasis, lymphovascular invasion, adjuvant radiotherapy and adjuvant chemotherapy were associated with cancer recurrence, while higher pathological tumor stage, more advanced age, lymph node metastasis, lymphovascular invasion and adjuvant radiotherapy were associated with disease specific survival. Patients with metastasis to regional lymph nodes (pT any N1-3) were at significantly higher risk for bladder cancer recurrence and death than patients with extravesical tumor extension (pT3N0), who in turn were at significantly higher risk than patients with organ confined disease (pT2 N0 or less). CONCLUSIONS: The results of this large, contemporary, multi-institutional series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and disease specific survival in patients with localized invasive transitional cell carcinoma.

Adult↗
PubMed2006

Cancer specific outcomes in patients with pT0 disease following radical cystectomy.

PURPOSE: We assessed clinical outcomes in patients found to have no evidence of disease, ie pT0, in the cystectomy specimen following radical cystectomy for transitional cell carcinoma. MATERIALS AND METHODS: Between 1984 and 2003, 955 consecutive patients underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer at 3 institutions, namely The Johns Hopkins Hospital, University of Texas Southwestern Medical Center and Baylor College of Medicine. Excluding nonTCC histology and patients with missing data resulted in 888 evaluable cases. Primary end points were recurrence-free survival and bladder cancer specific survival. RESULTS: Final pathological evaluation revealed absent transitional cell carcinoma in the cystectomy specimen, ie pT0, in 59 patients (7%), of whom 2 (3%) had pathologically positive lymph nodes. Transurethral resection stage or clinical stage data were available on 56 patients (95%), including Tis in 5 (9%), Ta in 2 (4%), T1 in 18 (32%), T2 in 29 (52%) and T3 in 2 (4%). Overall 6 recurrences (10%) were noted, including cTis in 1 case, cT1 in 1, cT2 in 3 and cT3 in 1. Median followup in patients with pT0 disease was 56 months (range 3 to 183). Three patients (5%) died of bladder cancer and another 4 (7%) died of other causes. Five and 10-year bladder cancer progression-free and cancer specific survival estimates in patients with pT0 disease were 90% and 81%, and 95% and 85%, respectively. CONCLUSIONS: Despite excellent clinical outcomes in the majority of patients with no evidence of tumor on final pathological evaluation not all patients with pT0 disease in the cystectomy specimen are cured of bladder cancer. These events may even occur in patients with nonmuscle invasive or muscle invasive organ confined pathology at staging transurethral resection. Further study is needed to identify prognostic factors in this population.

Adult↗
PubMed2006

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder.

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.

Aged↗
PubMed2005

Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy.

PURPOSE: We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. METHODS: A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. RESULTS: LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. CONCLUSION: LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.

Age Distribution↗
PubMed2005

Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy.

PURPOSE: Hypermethylation of the CpG island at the promoter region of the pi-class glutathione S-transferase gene (GSTP1) is the most common somatic genome abnormality in human prostate cancer. We evaluated circulating cell-free DNA GSTP1 CpG island hypermethylation as a prognostic biomarker in the serum of men with prostate cancer. EXPERIMENTAL DESIGN: Prostate cancer DNA GSTP1 CpG island hypermethylation was detected using a restriction endonuclease quantitative PCR technique. We analyzed preoperative serum from 85 men with clinically localized prostate cancer treated with radical prostatectomy and from 35 men with a negative prostate biopsy. We then assayed preoperative serum from a data set of 55 pairs of men with clinically localized prostate cancer treated with radical prostatectomy, matched for Gleason score, comprising 55 men suffering prostate-specific antigen (PSA) recurrence (median, 2 years) and 55 men who were free of disease at last follow-up (median, 3 years). The association of serum GSTP1 CpG island hypermethylation and PSA recurrence was determined. RESULTS: Circulating cell-free DNA with GSTP1 CpG island hypermethylation was not detected in the serum of men with a negative prostate biopsy but was detected in 12% of men with clinically localized disease and 28% of men with metastatic cancer (P = 0.003). In the matched data set, eight men (15%) who developed PSA recurrence were positive for DNA with GSTP1 CpG hypermethylation, whereas no patient who was free of disease was positive for GSTP1 CpG island hypermethylation (McNemar test, chi(2) = 6.1, P = 0.01). In a multivariable analysis that accounted for recognized prognostic factors, the presence of serum DNA with GTSP1 CpG island hypermethylation was the most significant predictor of PSA recurrence (hazard ratio, 4.4; 95% confidence interval, 2.2, 8.8; P < 0.001). CONCLUSION: Our study suggests that GSTP1 CpG island hypermethylation may be an important DNA-based prognostic serum biomarker for prostate cancer.

Adult↗
PubMed2004

Preoperative somatic symptoms are associated with disease progression in patients with bladder carcinoma after cystectomy.

BACKGROUND: A link between patient psychologic factors and bladder carcinoma outcome has not been demonstrated. The purpose of the current study was to assess the association of psychologic factors measured preoperatively with bladder carcinoma progression after cystectomy. METHODS: The Brief Symptom Inventory (BSI)-18 was administered prospectively to 65 patients with clinically localized bladder carcinoma before surgery. The BSI-18 measures distress in three specific domains-depression, anxiety, and somatization (i.e., distress due to somatic symptoms)-as well as general distress. Preoperative BSI-18 scores, tumor pathologic stage, and certain clinical variables were compared with disease status. Disease progression was defined as the development of either local disease recurrence or distant metastasis. Univariate and multivariate Cox proportional hazards models were constructed for statistical analysis. RESULTS: Of the 65 patients, 49 (79.4%) had no evidence of disease, 4 (6.2%) had local disease recurrence, and 12 (18.5%) had metastatic disease at last follow-up. The mean follow-up time was 1.3 years and did not differ significantly between survival outcomes (P = 0.577). Both tumor pathologic stage and preoperative somatic distress scores were associated with time to disease progression by univariate analysis (P = 0.038 and P = 0.055, respectively). After adjusting for tumor pathologic stage, a somatic distress score of > or = 2.00 was a significant predictor of disease progression (P = 0.044, hazard ratio = 3.31, 95% confidence interval = 1.03-10.60). Patient age, gender, reconstruction type, and BSI-18 scores for depression, anxiety, and general distress were not significantly associated with disease outcome. CONCLUSIONS: The authors found no correlation between psychologic symptoms measured preoperatively (i.e., depression, anxiety, and general distress) and bladder carcinoma progression. However, they reported an association between somatic symptoms and cancer outcome. If confirmed by other studies, these results may have important implications for the diagnosis, staging, and potential treatment of patients with bladder carcinoma.

Aged↗
PubMed2004

Prostate carcinogenesis and inflammation: emerging insights.

Prostate cancer remains a significant health concern for men throughout the world. Recently, there has developed an expanding multidisciplinary body of literature suggesting a link between chronic inflammation and prostate cancer. In support of this hypothesis, population studies have found an increased relative risk of prostate cancer in men with a prior history of certain sexually transmitted infections or prostatitis. Furthermore, genetic epidemiological data have implicated germline variants of several genes associated with the immunological aspects of inflammation in modulating prostate cancer risk. The molecular pathogenesis of prostate cancer has been characterized by somatic alterations of genes involved in defenses against inflammatory damage and in tissue recovery. A novel putative prostate cancer precursor lesion, proliferative inflammatory atrophy, which shares some molecular traits with prostate intraepithelial neoplasia and prostate cancer, has been characterized. Here, we review the evidence associating chronic inflammation and prostate cancer and consider a number of animal models of prostate inflammation that should allow the elucidation of the mechanisms by which prostatic inflammation could lead to the initiation and progression of prostate cancer. These emerging insights into chronic inflammation in the etiology of prostate carcinogenesis hold the promise of spawning new diagnostic and therapeutic modalities for men with prostate cancer.

Animals↗
PubMed2004

Molecular biomarker in prostate cancer: the role of CpG island hypermethylation.

CpG island hypermethylation may be one of the earliest somatic genome alterations to occur during the development of multiple cancers. Recently, aberrant methylation patterns for different tumors have been reported. We present a comprehensive review of the literature describing the role of CpG island hypermethylation of DNA from prostatic tissue and bodily fluids from men with prostate cancer. We reviewed the literature to evaluate CpG island hypermethylation in tissue and bodily fluids of men with primary and metastatic prostate cancer. Additionally, we reviewed the literature with respect to CpG island hypermethylation patterns in other urological malignancies. Using modern analytic methods, CpG island hypermethylation detection can be achieved. In men with prostate cancer, correlations between specific gene regulatory region hypermethylation analyses and Gleason score, pathologic stage and tumor recurrence have been demonstrated. CpG island hypermethylation may serve as a useful molecular biomarker for the detection and diagnosis of patients with prostate cancer.

CpG Islands↗