Nabil Chehade

Comparison of Biochemical Relapse-Free Survival Between Primary Gleason Score 3 and Primary Gleason Score 4 for Biopsy Gleason Score 7 Prostate Cancer

PURPOSE To determine whether the primary grade (PG) of biopsy Gleason score (GS) 7 prostate cancer (CaP) was predictive for biochemical relapse-free survival (bRFS). Most of the present data regarding the PG of GS7 CaP refer to surgical specimens. Our goal was to determine whether the biopsy GS used at the time of medical decision making predicted for the biochemical outcome. METHODS AND MATERIALS We reviewed the data from 705 patients with biopsy GS7 CaP, from a prospectively maintained database, who had been treated at our institution between September 1996 and March 2005 with radical prostatectomy (n = 310), external beam radiotherapy (n = 268), or prostate radioactive seed implantation (n = 127). The bRFS rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: PG of biopsy GS, initial prostate-specific antigen level, clinical T stage, use of androgen deprivation, risk group (high or intermediate), and treatment modality. RESULTS The 5-year bRFS rate was 78% and 71% (p = 0.0108) for biopsy GS7 PG3 CaP and biopsy GS7 PG4 CaP, respectively. Comparing PG3 and PG4 within treatment modalities, only prostate implantation patients had a significant difference in the 5-year bRFS rate, 88% vs. 76%, respectively (p = 0.0231). On multivariate analysis, the PG of biopsy GS remained an independent predictor of bRFS, with PG3 having better bRFS than PG4 (relative risk, 0.655; 95% confidence interval, 0.472-0.909; p = 0.0113). CONCLUSION Biopsy GS7 PG4 CaP carries a worse bRFS than biopsy GS7 PG3 CaP.

PSA Bounce and Biochemical Failure After Brachytherapy for Prostate Cancer: A Study of 820 Patients With a Minimum of 3 Years of Follow-Up

PURPOSE To determine clinical or dosimetric factors associated with a prostate-specific antigen (PSA) bounce, as well as an association between a PSA bounce and biochemical relapse-free survival (bRFS), in patients treated with iodine-125 brachytherapy. METHODS AND MATERIALS A variety of clinical and treatment factors were examined in 820 patients who had a minimum of 3 years of PSA follow-up with T1-T2cN0M0 prostate cancer. Four different PSA threshold values were used for defining a PSA bounce: a PSA rise of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL. RESULTS A PSA bounce of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL was noted in 247 patients (30.1%), 161 (19.6%), 105 (12.8%), and 78 (9.5%), respectively. The median time to the first PSA rise was 17.4, 16.25, 16.23, and 15.71 months, respectively, vs. 34.35 months for a biochemical failure (p < 0.0001). A PSA rise of ≥ 0.2 ng/mL was the only definition for which there was a significant difference in bRFS between bounce and non-bounce patients. The 5-year bRFS rate of patients having a PSA bounce of ≥0.2 was 97.7% vs. 91% for those who did not have a PSA bounce (p = 0.0011). On univariate analysis for biochemical failure, age, risk group, and PSAs per year had a statistically significant correlation with PSA bounce of ≥ 0.2 ng/mL. On multivariate analysis, age and PSAs per year remained statistically significant (p < 0.0001 and p = 0.0456, respectively). CONCLUSIONS A bounce definition of a rise ≥ 0.2 ng/mL is a reliable definition among several other definitions. The time to first PSA rise is the most valuable factor for distinguishing between a bounce and biochemical failure.

Five year biochemical recurrence free survival for intermediate risk prostate cancer after radical prostatectomy, external beam radiation therapy or permanent seed implantation

OBJECTIVE To compare biochemical recurrence-free survival (bRFS) for patients with intermediate-risk prostate cancer treated by retropubic radical prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), external beam radiation therapy (RT), or permanent seed implantation (PI). METHODS Patients treated for intermediate-risk prostate cancer per National Comprehensive Cancer Network guidelines from 1996 to 2005 were studied. Variables potentially affecting bRFS were examined using univariate and multivariate Cox regression analysis. Five-year bRFS rates were calculated by actuarial methods; bRFS was calculated using Kaplan-Meier analysis. Nadir +2 definition of biochemical failure was used for RT and PI patients; a PSA ≥ 0.4 ng/mL was used for radical prostatectomy (RP) patients. Time to initiation of salvage therapy was compared for each treatment group using the Kruskal-Wallis test. RESULTS Nine-hundred seventy-nine patients were analyzed with a median follow-up of 65 months. Five years bRFS rate was 82.8% for all patients (89.5% PI, 85.7% RT, 79.9% RRP, and 60.2% LRP). Patients treated by LRP had significantly worse bRFS than RT (P < .0001), PI (P < .0001), or RRP patients (P = .0038). Treatment modality (P < .0001) and average number of PSA tests per year (P < .0001) were the only independent predictors of bRFS on multivariate analysis. Median time to initiation of salvage therapy from time of treatment was 28.6 months for all patients (26.1 RP, 21.0 LRP, 47.4 PI, 47.8 RT; P < .0001). CONCLUSIONS Patients with intermediate-risk prostate cancer choosing PI, RT, or RRP appear to have improved 5-year bRFS and delayed salvage therapy compared with LRP.

Long-term (10-year) gastrointestinal and genitourinary toxicity after treatment with external beam radiotherapy, radical prostatectomy, or brachytherapy for prostate cancer.

Objective.To examine gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated in 1999 with external beam radiotherapy (RT), prostate interstitial brachytherapy (PI) or radical prostatectomy (RP). Methods. TThe records of 525 patients treated in 1999 were reviewed to evaluate toxicity. Late GI and GU morbidities were graded according to the RTOG late morbidity criteria. Other factors examined were patient age, BMI, smoking history, and medical co-morbidities. Due to the low event rate for late GU and GI toxicities, a competing risk regression (CRR) analysis was done with death as the competing event. Results. Median follow-up time was 8.5 years. On CRR univariate analysis, only the presence of DM was significantly associated with GU toxicity grade >2 (P = 0.43, HR 2.35, 95% Cl = 1.03–5.39). On univariate analysis, RT and DM were significantly associated with late GI toxicity. On multivariable analysis, both variables remained significant (RT: P = 0.038, HR = 4.71, CI = 1.09–20.3; DM: P = 0.008, HR = 3.81, 95% Cl = 1.42–10.2). Conclusions. Late effects occur with all treatment modalities. The presence of DM at the time of treatment was significantly associated with worse late GI and GU toxicity. RT was significantly associated with worse late GI toxicity compared to PI and RP.

The Importance of Serum Prostate-specific Antigen Testing Frequency in Assessing Biochemical and Clinical Failure After Prostate Cancer Treatment

OBJECTIVES To assess the relationship between prostate-specific antigen (PSA) testing frequency and biochemical failure (bF) and clinical failure (cF). METHODS The records of 5616 patients with low-, intermediate-, or high-risk prostate cancer treated (brachytherapy, external beam radiotherapy, or surgery) between 1996 and 2007 were reviewed. Factors influencing bF and cF were recorded including age, initial PSA, androgen deprivation, race, clinical stage, biopsy Gleason score, and the frequency of follow-up PSA testing. Univariate and multivariate analyses were performed to assess the effect of these factors on bF and cF. Sensitivity and specificity were calculated to determine the optimal frequency of PSA testing. RESULTS The median follow-up is 45 months. The median number of PSA tests per year before the occurrence of bF and cF is 1.9 for both endpoints. The multivariate analysis of factors significantly associated with bF and cF demonstrate that PSA frequency, initial PSA, clinical stage, and biopsy Gleason score are independently predictive of outcome. PSA testing achieves the best sensitivity and specificity when 2 PSA tests are drawn per year for both bF (sensitivity = 66.3%, specificity = 58.0%) and cF (sensitivity = 75.1%, specificity = 60.3%). CONCLUSIONS The frequency of PSA testing is strongly associated with the detection of bF and cF. Because it is a variable that can be controlled, PSA testing frequency should be standardized to minimize spurious conclusions from studies with bF and cF endpoints. The sensitivity and specificity can be optimized by obtaining 2 PSA tests per year.

Long-term toxicity and associated cost of initial treatment and subsequent toxicity-related intervention for patients treated with prostatectomy, external beam radiotherapy, or brachytherapy: A SEER/Medicare database study.

4 Background: Treatment-related toxicity for prostate cancer (CaP) is rarely reported more than 5 years after therapy. We examined the SEER-Medicare linked database with the potential of having 16 years of follow-up data on toxicity requiring procedural intervention. METHODS The SEER-Medicare database was queried for CaP patients treated with prostatectomy (RP), external beam radiotherapy (EBRT), or brachytherapy (PI) between 1991-2007. We identified procedural billing codes associated with toxicity-related treatments. We obtained information on the Medicare reimbursement rates for the initial treatment and any toxicity-related interventions. We then computed the cost per patient-year within each treatment modality over time. RESULTS A total of 137,427 patients who were 65 years or older at the time of CaP diagnosis and who had CaP as their only cancer diagnosis were retrieved from the SEER/Medicare database: 59,559 (43.3%) treated with RP, 60,806 (44.2%) treated with EBRT, and 17,062 (12.4%) treated with PI. No patient received combined therapy. The median follow-up is 71 months. Overall, 10,585 (7.3%) patients experienced a toxicity requiring intervention. Within treatment modalities, the percentages receiving toxicity-related intervention were: RP 6.9%, EBRT 8.8%, and PI 3.7%. The gastrointestinal (GI) and genitourinary (GU) toxicity comparisons are listed in the table. Dilation of a urethral stricture was the most common GU toxicity (3.6% of all patients) while cauterization of rectal bleeding was the most common GI toxicity (0.8% of all patients). CONCLUSIONS The long-term toxicity and cost per patient-year of the major prostate cancer treatment modalities differ. EBRT is the most toxic and most costly. [Table: see text].

Variations in treatment modality use for the definitive management of prostate cancer in the United States.

174 Background: No prospective, randomized comparative efficacy trial exists to guide treatment of definitively managed prostate cancer patients. Despite this, treatment selection varies nationally and we attempt to assess these patterns of use. METHODS The SEER database was queried to identify cases of prostate cancer diagnosed between 1998-2008. The modalities identified were brachytherapy (brachy), combination of brachytherapy and external beam radiation (CombRT), external beam radiotherapy (EBRT), radical prostatectomy and external beam radiotherapy (RP+RT), and radical prostatectomy (RP). The number of cases by year, patient age and SEER region was computed. RESULTS There were 361,135 men in this analysis: 12.4% brachy, 6.8% CombRT, 27.5% EBRT, 3.1% RP+RT, and 50.3% RP. As expected, treatment modality varied by age with younger men more likely to receive RP and older man more likely to receive EBRT or brachy. There was some variation in choice of treatment modality over time: 6.6% for brachy; 4.2% for CombRT; 1.9% for EBRT; 2.0% for RP+RT; and 7.8% for RP. The variation in treatment modality by region was surprisingly wide (table): 14.4% for brachy; 25.5% for CombRT; 28.5% for EBRT; 3.8% for RP+RT; and 26.8% for RP. CONCLUSIONS Choice of prostate cancer treatment modality varies by age, year of treatment, and most notably geographical region. Surprisingly the changes in reimbursement rates over the study period seem to have had minimal impact on choice of treatment modality. The regional variation implies that affiliations among healthcare providers significantly impact treatment. [Table: see text].

Comparing long-term toxicity between external beam radiotherapy modalities: A SEER/Medicare database study.

118 Background: The use of intensity modulated radiotherapy (IMRT) for the treatment of prostate cancer (CaP) has been widely promoted due to the hypothesized benefit of low late toxicity. METHODS The SEER-Medicare database was queried for CaP patients treated with external beam radiotherapy (EBRT), 1991-2007. CPT billing codes were used to identify patients treated with IMRT or standard EBRT (sEBRT), which was comprised of conformal radiotherapy or a four-field technique. Patients without a treatment billing code were excluded from the analysis. Information on dose is unavailable. CPT codes were also used to identify procedures associated with gastrointestinal (GI) or genitourinary (GU) toxicity related treatments. Cumulative incidence rates for GI and GU toxicity were calculated with death treated as a competing event. RESULTS A total of 137,427 patients who were 65 years or older at the time of CaP diagnosis and who had CaP as their only cancer diagnosis were retrieved from the SEER-Medicare database: 60,806 were treated with EBRT and a treatment billing code was identified for 35,388 patients. No patient received combined therapy. Seventeen percent of patients received IMRT. The median follow-up for patients receiving IMRT is 40 months (mo) (range 2-157) vs 77 mo (range 0-203) for patients receiving sEBRT. Overall, 3,699 (10%) patients experienced a toxicity requiring an intervention. The five year rate of GI The gastrointestinal (GI) and genitourinary (GU) toxicity comparisons are listed in the table. For both endpoints, rate of toxicity at five years was higher for the IMRT group. The most common GU toxicity for both groups was dilation of a urethral stricture (3.8% of all sEBRT patients vs 3.4 of all IMRT patients). Cauterization of rectal bleeding was the most common GI toxicity (2.4% of all sEBRT patients vs 1.6 of all IMRT patients). CONCLUSIONS While the rates of GI toxicity between IMRT and sEBRT are comparable, of concern is the higher rate of GU toxicity for the IMRT patients despite this group having a shorter follow up than the sEBRT group. [Table: see text].