Risk Of Prostate-specific Antigen Failure Research Articles

Radical Prostatectomy for High-risk Prostate Cancer Defined by Preoperative Criteria: Oncologic Follow-up in National Multicenter Study in 813 Patients and Assessment of Easy-to-use Prognostic Substratification

To estimate the effect of predictive factors for oncologic outcomes after radical prostatectomy (RP) for high-risk prostate cancer (PCa). A total of 813 patients underwent RP for high-risk PCa in a national retrospective multi-institutional study. High-risk PCa was defined as follows: prostate-specific antigen (PSA) level>20 ng/mL, Gleason score 8-10, and/or clinical Stage T2c-T4 disease. The preoperative criteria of high-risk PCa were studied in a logistic regression model to assess the correlations with the pathologic findings in the RP specimens. The predictive factors isolated or combined in scores were assessed by Cox multivariate and Kaplan-Meier analyses in predicting PSA failure (recurrence-free survival [RFS]) and overall survival (OS). The median follow-up was 64 months. Organ-confined disease was reported in 36.5%. The 5-year RFS, metastasis-free survival, and OS rate was 74.1%, 96.1%, and 98.6%, respectively. Each preoperative criteria of high-risk PCa was an independent predictor of PSA failure. The PSA failure risk was increased by 1.5- and 2.8-fold in men with 2 and 3 criteria, respectively. The RFS, but not the OS, was significantly different according to the preoperative score (P<.001). The postoperative score was significantly predictive for RFS and OS (P<.001 and P<.035, respectively). The risk of PSA failure was significantly increased with an increasing postoperative score (2-4.6-fold). National data support evidence that RP can result in encouraging midterm oncologic outcomes for the management of high-risk PCa. At 5 years after surgery, 75% of patients remain disease free. Our easy-to-use risk stratification might help clinicians to better predict the clinical and PSA outcomes of high-risk patients after surgery.

720 TIME TO PROGRESSION IN PATIENTS WITH PROSTATE CANCER: A COMPARISON OF CONTINUOUS DEGARELIX VERSUS DEGARELIX FOLLOWING LEUPROLIDE TREATMENT

You have accessJournal of UrologyProstate Cancer: Advanced1 Apr 2011720 TIME TO PROGRESSION IN PATIENTS WITH PROSTATE CANCER: A COMPARISON OF CONTINUOUS DEGARELIX VERSUS DEGARELIX FOLLOWING LEUPROLIDE TREATMENT E David Crawford, Judd W Moul, Neal Shore, Egbert van der Meulen, and Bo-Eric Persson E David CrawfordE David Crawford Denver, CO More articles by this author , Judd W MoulJudd W Moul Durham, NC More articles by this author , Neal ShoreNeal Shore Myrtle Beach, SC More articles by this author , Egbert van der MeulenEgbert van der Meulen Copenhagen, Denmark More articles by this author , and Bo-Eric PerssonBo-Eric Persson Saint−Prex, Switzerland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1688AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The efficacy of the gonadotropin-releasing hormone (GnRH) blocker degarelix was compared with the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide during a pivotal 1-year randomized phase III trial (CS21). We report long-term prostate-specific antigen (PSA) results from the ongoing 5-year extension study (CS21A). METHODS In CS21, patients with prostate cancer (all stages) received degarelix 240 mg at month 1 and then a maintenance dose of either 80 mg (n=207) or 160 mg (n=202) monthly, or leuprolide 7.5 mg/month (n=201). After 1 year, 384 patients entered CS21A; 134 who had received leuprolide were re-randomized to degarelix 240/80 mg or 240/160 mg. PSA progression-free survival (PFS) was defined as time to first of PSA failure (2 consecutive increases in PSA of 50% and ≥5 ng/mL compared with nadir) or death. The time for 25% of patients to experience PSA failure or death (TTP 25%) was analyzed by Weibull estimates. RESULTS During year 1, the risk of PSA failure or death was significantly lower with degarelix 240/80 mg vs leuprolide (p=0.05, log-rank); in patients with baseline PSA >20 ng/mL, time to PSA failure was also significantly longer with degarelix (p=0.0436; log-rank). At 27.5 months' median follow-up, PSA PFS hazard rate was significantly reduced in patients switching from leuprolide to degarelix (from 0.20 to 0.08 events/year; p=0.003); similar PSA PFS hazard improvements were seen in patients with baseline PSA >20 ng/mL (p=0.031). TTP 25% in this patient subgroup was also longer with degarelix vs leuprolide for the 1-year data (407 vs 303 days; p=0.085 [Figure]); an analysis of degarelix data beyond 1 year showed an even greater difference (median difference 210 days; p=0.01). CONCLUSIONS During CS21, PSA PFS was significantly improved with degarelix compared with leuprolide. In CS21A, patients initially receiving leuprolide had a significantly lower rate of PSA failure or death after switching to degarelix; the same pattern occurred in patients with baseline PSA >20 ng/mL. TTP 25% was also significantly longer with degarelix in this patient subgroup. These findings support the durability of the significant benefit for degarelix over leuprolide observed during the first year and the use of degarelix as first-line androgen deprivation therapy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e289-e290 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information E David Crawford Denver, CO More articles by this author Judd W Moul Durham, NC More articles by this author Neal Shore Myrtle Beach, SC More articles by this author Egbert van der Meulen Copenhagen, Denmark More articles by this author Bo-Eric Persson Saint−Prex, Switzerland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Smoking, Obesity, and Statin Therapy in the Prognosis of Prostate Cancer

TO THE EDITOR: Gutt et al documented fewer recurrences among men with radiation-treated prostate cancer who had received statin therapy during or after their radiation therapy. They interpreted their observations to indicate a favorable influence by statins on prostate cancer behavior, a conclusion that is not appropriate unless observations are controlled for host factors that may have influenced tumor behavior. Most studies examining relationships between smoking and prostate cancer recurrence or tumor-related mortality demonstrate smoking-related increases in both, even after controlling for multiple factors including the more advanced malignant disease at presentation and the smaller prostate size characteristic of smokers. In a study similar to that of Gutt et al, Pantarotto et al reported follow-up data from 434 patients after external-beam radiation therapy with curative intent. In patients who had been current smokers at the time of therapy, they found a recurrence rate 5.2 times greater than the rate of life-long nonsmokers, and in former smokers, the recurrence rate was 2.9 times greater. Studies examining relationships between obesity and prostate cancer recurrence or tumor-related mortality have demonstrated an inconsistent pattern. Gong et al retrospectively analyzed tumor characteristics, body mass index (BMI), and smoking habits in 752 patients with prostate cancer and reported that prostate cancer–specific mortality was doubled in men with a BMI 30 kg/m compared with men who were less obese and that this mortality was 2.3 times as great in smokers compared with nonsmokers. Freedland et al reported a 2.09-fold increased risk of prostate-specific antigen failure in severely obese men (BMI 35 kg/m) and, in a recent review, concluded that obesity may reduce the risk of nonaggressive disease but increase the risk of aggressive disease, especially in those with BMI 35 kg/m. These observations suggest that if smokers in the study by Gutt et al had been less likely to receive statins either because of their lower average weight and associated lower lipid values or because of a lower level of interest in maintaining optimal health, then statin consumers would have included lower percentages of smokers, contributing to a lower frequency of tumor recurrences among them, and that the distribution of obese men might also have influenced recurrence rates. Analysis of BMI and smoking habits of their patients would increase the value of their analysis, while adding to the body of information that eventually should help to define any influence that statin therapy might have on prostate cancer behavior.

Tumor Volume Changes on 1.5 Tesla Endorectal MRI During Neoadjuvant Androgen Suppression Therapy for Higher-Risk Prostate Cancer and Recurrence in Men Treated Using Radiation Therapy Results of the Phase II CALGB 9682 Study

We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST.

Duration of neoadjuvant androgen deprivation therapy before radical prostatectomy and disease-free survival in men with prostate cancer

There is little evidence that neoadjuvant androgen deprivation therapy (ADT) of 3 months’ duration before radical prostatectomy (RP) favorably influences disease-free survival. However, recent data suggest that prolonged treatment may improve outcome. We conducted a prospective cohort study to determine whether ADT of either standard or prolonged duration before RP influences the risk of prostate-specific antigen (PSA) failure. We followed 756 men treated for prostate cancer by RP between 1991 and 1998 in Quebec City. Of these, 240 received combined neoadjuvant ADT for either ≤92 days (129 men) or ≥93 days (111 men), and 516 were treated by RP alone. Multivariate Cox regression was used to estimate the hazard ratios (HR) of PSA failure (>0.3 ng/mL) associated with treatment regimen controlling for age, clinical stage, grade, and initial PSA level. The median duration of follow-up was 4 years. Compared with men treated by RP alone, those who received neoadjuvant ADT for ≥93 days had an HR of PSA failure of 0.60. The inverse association with the risk of PSA failure became statistically significant from the third year on, reached its greatest magnitude after 4 years, and was still present 8 years after RP. No association was observed for ADT of ≤92 days. These results suggest that neoadjuvant ADT before RP has a real, delayed, and persistent effect on disease-free survival, if and only if ADT is prolonged beyond 3 months.

NEOADJUVANT HORMONAL THERAPY BEFORE RADICAL PROSTATECTOMY AND RISK OF PROSTATE SPECIFIC ANTIGEN FAILURE

To date there is little information on the long-term effect of neoadjuvant hormonal therapy on prostate cancer progression. We performed a prospective study to determine whether patients with prostate cancer receiving neoadjuvant hormonal therapy before radical prostatectomy (hormonal therapy group) have a lower risk of prostate specific antigen (PSA) failure than those treated with radical prostatectomy alone (prostatectomy group). We also evaluated whether type of neoadjuvant hormonal therapy and duration were associated with the risk of PSA failure. We followed 680 men initially treated for prostate cancer with radical prostatectomy between January 1988 and December 1997 at our university hospital. Of the patients 292 received neoadjuvant hormonal therapy. Median followup was 38 months. Cox regression analysis was used to assess the association between neoadjuvant hormonal therapy and PSA failure (greater than 0.3 ng./ml.) controlling for age, clinical stage, grade, initial PSA and adjuvant therapies. Surgical margins were positive less often in the hormonal therapy (25%) than the prostatectomy (47%) group (p = 0.0001). PSA failure was observed in 163 patients and the 5-year failure rate was 33%. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups (hazards ratio 0.94, 95% confidence interval 0.68 to 1.30). Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy.