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Alan W Partin

Publications and source records attributed to Alan W Partin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy.

CONTEXT: The natural history of biochemical recurrence after radical prostatectomy can be long but variable. Better risk assessment models are needed to identify men who are at high risk for prostate cancer death early and who may benefit from aggressive salvage treatment and to identify men who are at low risk for prostate cancer death and can be safely observed. OBJECTIVES: To define risk factors for prostate cancer death following radical prostatectomy and to develop tables to risk stratify for prostate cancer-specific survival. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 379 men who had undergone radical prostatectomy at an urban tertiary care hospital between 1982 and 2000 and who had a biochemical recurrence and after biochemical failure had at least 2 prostate-specific antigen (PSA) values at least 3 months apart in order to calculate PSA doubling time (PSADT). The mean (SD) follow-up after surgery was 10.3 (4.7) years and median follow-up was 10 years (range, 1-20 years). MAIN OUTCOME MEASURE: Prostate cancer-specific mortality. RESULTS: Median survival had not been reached after 16 years of follow-up after biochemical recurrence. Prostate-specific doubling time (<3.0 vs 3.0-8.9 vs 9.0-14.9 vs > or =15.0 months), pathological Gleason score (< or =7 vs 8-10), and time from surgery to biochemical recurrence (< or =3 vs >3 years) were all significant risk factors for time to prostate-specific mortality. Using these 3 variables, tables were constructed to estimate the risk of prostate cancer-specific survival at year 15 after biochemical recurrence. CONCLUSION: Clinical parameters (PSADT, pathological Gleason score, and time from surgery to biochemical recurrence) can help risk stratify patients for prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. These preliminary findings may serve as useful guides to patients and their physicians to identify patients at high risk for prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy to enroll them in early aggressive treatment trials. In addition, these preliminary findings highlight that survival in low-risk patients can be quite prolonged.

Aged↗
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↗
PubMed2005

Stronger association between obesity and biochemical progression after radical prostatectomy among men treated in the last 10 years.

BACKGROUND: Prior prospective cohort studies found that obesity was associated with increased risk of prostate cancer death. However, in the last 20 years dramatic changes in both the extent of obesity and prostate cancer screening and treatment have occurred. Whether the association between obesity and aggressive disease has changed as a result of these temporal changes is unclear. METHODS: The study population consisted of 2,832 men treated by anatomic radical retropubic prostatectomy between 1985 and 2004 by a single surgeon. We evaluated the associations of obesity (body mass index > or =30 kg/m(2))with tumor stage and grade using logistic regression and with biochemical progression using Cox proportional hazards regression. We examined whether these associations have changed over the last 20 years. RESULTS: On multivariable analysis, the strength of the positive association between obesity and high-grade disease increased over time whereas the strength of the positive association between obesity and positive surgical margins decreased over time. The strength of the positive association between obesity and extraprostatic extension fluctuated over time, although the strongest and only statistically significant association was among men treated since 2000. The association between obesity and biochemical progression was strongest among men treated since 1995 (relative risk, 1.90; 95% confidence interval, 1.09-3.30; P = 0.02). CONCLUSIONS: In the current study, with the exception of positive surgical margins, the positive association between obesity and high-grade disease, advanced stage, and biochemical progression after radical retropubic prostatectomy was in general strongest among men treated in the last 10 years. The reasons for these findings are not clear, although factors possibly related to prostate-specific antigen-based screening and/or other temporal changes in prostate cancer diagnosis and treatment may play a role.

Body Mass Index↗
PubMed2005

Efficacy of continuous local anesthetic infusion for postoperative pain after radical retropubic prostatectomy.

OBJECTIVES: To determine whether a subfascial continuous infusion of local anesthetic in patients undergoing radical retropubic prostatectomy would result in a reduction in postoperative opioid requirements and an improvement in pain scores. METHODS: This was a prospective, double-blind, placebo-controlled, randomized trial in patients undergoing elective radical retropubic prostatectomy. A small catheter was placed subfascially at the end of surgery and attached to an elastomeric pump that administered either 0.5% bupivacaine or normal saline into the wound at a rate of 2 mL/hr until discharge on postoperative day 3. The outcomes assessed included the dosage of hydromorphone used by a patient-controlled analgesic system, a visual analog scale (VAS) for pain at rest and with activity, a VAS of nausea, and length of hospital stay. RESULTS: A total of 100 patients were successfully randomized, with all patients completing the protocol. No differences were found between the groups with regard to VAS pain at rest, VAS pain with activity, intravenous or oral analgesic consumption, or VAS nausea scores. CONCLUSIONS: Continuous subfascial infusion of local anesthetic did not result in a postoperative reduction in opioid requirements or an improvement in pain scores in patients undergoing radical retropubic prostatectomy.

Anesthetics, Local↗
PubMed2005

Kinetics of tumor growth of prostate carcinoma estimated using prostate-specific antigen.

OBJECTIVES: To investigate whether the second-order kinetics model of prostate-specific antigen (PSA) increase would be more appropriate in some cases than the traditionally assumed first-order model. PSA levels are used to detect tumor recurrence after radical prostatectomy, and the rate of PSA increase is used to predict patients' prognosis. METHODS: Sequential PSA values from 147 patients showing detectable PSA after radical prostatectomy were analyzed by nonlinear regression analysis. The best-fitting model was chosen using the lowest sum of squares residual error. RESULTS: Of the 147 cases, 90 (61.2%) followed the first-order kinetics, and 57 (38.8%) were better described by second-order kinetics. The order of PSA increase correlated with the Gleason score of the tumor in the radical prostatectomy specimens. The first-order kinetics were associated with tumors with Gleason scores of 5 to 6, 7, and 9, and the second-order kinetics were associated with tumors with a Gleason score of 8 (P < 0.01). Our data did not show a correlation between the order of PSA increase and the clinical prognosis. CONCLUSIONS: The presence of a group of tumors in which the increase in PSA follows second-order kinetics is significant. Such an increase may be associated with an autocatalytic mechanism assisting tumor growth. The existence of such a mechanism requires additional investigation.

Humans↗
PubMed2005

Comparison of predictive accuracy for pathologically organ confined clinical stage T1c prostate cancer using human glandular kallikrein 2 and prostate specific antigen combined with clinical stage and Gleason grade.

PURPOSE: Previously human glandular kallikrein 2 (hK2) has been implicated to predict pathologically organ confined prostate cancer (PCa) in patients with stage T2 disease. Now we evaluated the usefulness of hK2, as measured by 2 entirely different immunoassay designs, to enhance the discrimination of pathologically organ from nonorgan confined clinical stage T1c PCa. MATERIALS AND METHODS: A consecutive series of pretreatment serum from 148 men with clinical stage T1c PCa was used in 2 equally sensitive and specific methods to measure total hK2 with independent reagents and entirely different assay designs. Total prostate specific antigen (tPSA) and free PSA (fPSA) were measured and percent fPSA was calculated. We determined the algorithm, hK2*tPSA/fPSA, from data generated by each hK2 assay, calculated means, medians and ranges for each analyte and algorithm, and calculated the significance of differences on univariate analysis. Using pretreatment PSA, clinical stage and biopsy Gleason grade we then developed a multivariate logistic regression base model to predict organ confined cancer and we compared predictions of the base model supplemented by the different hK2 measurements. RESULTS: hK2 and hK2 based algorithms obtained by each hK2 assay were significantly different for pT2a/b vs pT3a or greater PCa (p = 0.034 to 0.0001) compared to tPSA (p = 0.06), fPSA (p = 0.90) or percent fPSA (p = 0.059). However, AUC (0.67 to 0.70) calculated by ROC analysis of the 4 models containing hK2 derived information was not significantly larger than that of the base model (AUC = 0.64, p = 0.52). CONCLUSIONS: The current data confirm that hK2 alone or hK2*tPSA/fPSA measured by 2 immunoassays is significantly lower in men with pT2a/b vs pT3a or greater PCa compared to tPSA, fPSA or percent fPSA on univariate analysis of a validation set of clinical stage T1c prostate cancer treated at an American center of excellence for prostate cancer surgery. However, the incorporation of preoperative hK2 into multiparameter predictive models for pT2 cancers did not increase predictive accuracy in this cohort of men.

Adult↗
PubMed2005

Serum leptin and pathological findings at the time of radical prostatectomy.

PURPOSE: Obesity has been associated with a higher risk of progression following radical prostatectomy (RP). Obese men have higher serum leptin, a hormone produced by adipocytes, which has also been shown to be an in vitro prostate cancer growth factor. We examined whether serum leptin correlates with advanced pathological findings at RP. MATERIALS AND METHODS: Preoperative serum from 225 men treated with RP between 1998 and 1999 was examined for serum leptin. Multivariate logistic regression analysis was used to determine whether serum leptin was predictive of extraprostatic extension (pT3a). RESULTS: Serum leptin highly correlated with body mass index (Spearman r = 0.602, p <0.001). Serum leptin was not associated with total or percent free prostate specific antigen (PSA), biopsy or prostatectomy Gleason score, age or height. On multivariate analysis with total and percent free PSA, clinical stage, age, biopsy Gleason score, body mass index, serum leptin, and height as variables considered for entry into the model, serum PSA (p = 0.009), clinical stage (p = 0.019) and serum percent free PSA (p = 0.041) were the only variables predictive of extraprostatic extension. Serum leptin was not significantly associated with pathological stage (pT3a). CONCLUSIONS: In the current study of predominantly white men with mainly low risk disease there was no statistically significant association between serum leptin and pathological stage (pT3a) at RP. In this cohort serum leptin was not a good biomarker for predicting advanced stage at RP.

Humans↗
PubMed2005

Obesity and risk of biochemical progression following radical prostatectomy at a tertiary care referral center.

PURPOSE: We have previously reported that obesity is an independent predictor of biochemical progression after radical prostatectomy (RP) in men treated by a single surgeon at our institution. We sought to validate or refute these findings using data on men treated by multiple other surgeons at our institution. MATERIALS AND METHODS: The study population consisted of 2,796 men treated with anatomical radical RP between 1988 and 2004 by 1 of 17 surgeons at our institution, a tertiary care referral center. We evaluated the association between body mass index (BMI), and adverse pathological features and biochemical progression. RESULTS: On multivariate analysis increased BMI was associated with high grade disease in the RP specimen (p = 0.03), positive surgical margins (p <0.001), extraprostatic extension (p <0.001) and lymph node metastasis (p = 0.01) but not with seminal vesicle invasion (p = 0.59). After multivariate adjustment for preoperative clinical characteristics increased BMI was significantly associated with an increased risk of biochemical progression (p <0.001), which was somewhat but not completely attenuated by further adjusting for RP specimen pathological features (p = 0.03). Adjustment for surgeon did not affect these results. CONCLUSIONS: In men undergoing RP increased BMI was associated with adverse pathological features and a greater risk of biochemical progression. These findings together with the results of several recently published series collectively provide strong evidence that obese men undergoing RP are more likely to have aggressive prostate cancer.

Aged↗
PubMed2005

Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy.

PURPOSE: Adiponectin is a polypeptide hormone produced by adipocytes that has anti-angiogenic properties. Circulating adiponectin is lower in obese men. Obesity has been associated with advanced stage and a higher risk of biochemical progression following radical prostatectomy (RP) in several series. We examined whether serum adiponectin is associated with advanced disease stage at RP. MATERIALS AND METHODS: Adiponectin was measured by enzyme-linked immunosorbent assay in the preoperative serum of 236 men treated with RP between 1998 and 1999. The odds ratio (OR) of advanced stage (pT3a or greater) and high grade disease (pathological Gleason sum 7 or greater) associated with quartiles of adiponectin were estimated using multivariate logistic regression models. RESULTS: Serum adiponectin weakly correlated inversely with body mass index (Spearman r = -0.22, p = 0.01). Serum adiponectin was not associated with cancer stage or grade. However, in normal weight men adiponectin was positively associated with high stage disease (OR 1.14, 95% CI 1.02 to 1.29, p = 0.03), although there was no statistically significant association with high grade disease (OR 1.05, 95% CI 0.94 to 1.18, p = 0.38). In overweight and obese men adiponectin was inversely associated with high grade disease (OR 0.94, 95% CI 0.87 to 1.01, p = 0.09), although there was no statistically significant association with high stage disease (OR 0.97, 95% CI 0.91 to 1.04, p = 0.43). Further adjustments for body mass index had little impact on any ORs. CONCLUSIONS: These data provide evidence to suggest that adiponectin may be related to prostate cancer aggressiveness, although the direction of the associations may depend on the extent of adiposity and on cancer grade.

Adiponectin↗
PubMed2005

The prostatic specific antigen era is alive and well: prostatic specific antigen and biochemical progression following radical prostatectomy.

PURPOSE: Prostate specific antigen (PSA) has been shown to predict the presence of prostate cancer on biopsy, pathological stage, and biochemical progression following primary therapy. A recent study found only a weak association between PSA and tumor volume in the radical prostatectomy (RP) specimen and concluded that the PSA era is over. We examined the association between PSA and clinical progression in men undergoing RP. MATERIALS AND METHODS: The study population consisted of 2,312 men treated with RP between 1992 and 2004 by a single surgeon. We evaluated the association between preoperative PSA and biochemical progression on multivariate analysis. RESULTS: Men with higher preoperative PSA concentrations had higher grade cancers in the biopsy and RP specimen, and more adverse pathological features. After adjusting for the clinical covariates of age, race, grade, stage, and year of surgery, preoperative PSA was significantly associated with the risk of biochemical progression. When only men with PSA less than 10 ng/ml were examined, PSA remained a significant predictor of biochemical progression on multivariate analysis (RR 1.30, 95% CI 1.18 to 1.44, p <0.001). For each 2-point increase in PSA, the risk of biochemical progression increased approximately 2-fold. CONCLUSIONS: Preoperative PSA was significantly associated with high grade disease and adverse pathological findings. After adjusting for clinical covariates, PSA was significantly associated with the risk of biochemical progression, even in men with PSA less than 10 ng/ml. Despite multiple limitations, PSA remains the best prostate cancer tumor marker available.

Disease Progression↗
PubMed2005

Obesity and capsular incision at the time of open retropubic radical prostatectomy.

PURPOSE: The goal of radical prostatectomy (RP) is complete removal of the intact prostate. Obese men can represent a technical challenge. However, to our knowledge objective data linking obesity with technically inferior surgery are lacking. Therefore, we examined the association between body mass index (BMI) and capsular incision at RP as a surrogate of a poor technical operation in men treated for prostate cancer by several high volume surgeons at a center of excellence. MATERIALS AND METHODS: The study population consisted of 7,027 men treated with anatomical retropubic RP between 1996 and 2004 by 7 high volume surgeons. We evaluated the association between BMI and capsular incision using logistic regression, adjusting for clinical and pathological variables, and for the surgeon. RESULTS: Overall capsular incision was noted in 4.6% of all RP specimens. After adjustment for preoperative prostate specific antigen, patient race, height, year of surgery, clinical stage, pathological Gleason sum, prostate weight, extraprostatic extension and seminal vesicle invasion increased BMI was associated with increased odds of capsular incision (p trend = 0.005). After further adjustment for surgeon mild obesity was associated with 30% increased odds of capsular incision (OR 1.30, 95% CI 0.92 to 1.83), while moderate and severe obesity was associated with 57% increased odds of capsular incision (OR 1.57, 95% CI 0.82 to 3.00) relative to normal weight men (p trend = 0.06). CONCLUSIONS: In a study of more than 7,000 men treated by 7 experienced surgeons BMI was positively related to capsular incision. This suggests that open retropubic RP is technically more difficult in obese men, which results in a greater likelihood of a less than technically ideal operation. Although this may be predicted to have a negative impact on disease-free survival outcomes in obese men, it is unlikely to alone explain the worse outcomes in obese men noted in previous RP series.

Aged↗
PubMed2005

Surgical margin status after radical retropubic prostatectomy.

This month there are two mini-reviews on aspects of prostate cancer. The first, from the USA, presents the implications of surgical margin status after radical prostatectomy and the potential role of adjuvant radiation therapy. The second, from the USA and Belgium, discusses the use of hormonal therapy for PSA-only recurrence of prostate cancer after previous local therapy. In the third mini-review, the condition known as hypoactive sexual desire disorder is described, and that it is often ignored or erroneously treated as erectile dysfunction suggests to the authors that education of doctors and patients is required. Finally, there is a mini-review of conventional and alternative methods for providing analgesia in renal colic.

Adenocarcinoma↗