Difference In bPFS Research Articles

Long-term prognosis and prognostic factors of brachytherapy and propensity score matched comparisons of the outcomes between brachytherapy and radical prostatectomy: a retrospective cohort study.

To report outcomes of patients undergoing brachytherapy (BT), investigate factors associated with biochemical progression-free survival (bPFS) and to compare its long-term prognosis with that of radical prostatectomy (RP) in localized prostate cancer. The clinical data of 87 elderly patients with localized prostate cancer who underwent BT at Huadong Hospital affiliated to Fudan University from January 2009 to December 2016 were retrospectively analyzed. Patient prognoses and associated factors were investigated using univariate and multivariate Cox regression models. The clinical data of the 142 patients with localized prostate cancer who underwent RP during the same period were also collected. By using propensity score matching (PSM), the 42 patients who underwent BT were matched to 42 patients who underwent RP, and the differences in the survival curves were investigated using the Kaplan-Meier method. The median follow-up period of the patients who underwent BT was 101 months. The 5- and 10-year overall survival (OS) rates of the patients who underwent BT were 82.8% and 64.0%, respectively, while the 5- and 10-year bPFS rates were 97.2% and 87.5%, respectively. The preoperative clinical Tumor (T) stage was identified as a prognostic factor of bPFS, as patients who underwent BT whose clinical stage was T3 had a worse prognosis than those whose clinical stage was T1-T2 (HR =0.097, P=0.049). After PSM, the average follow-up time of the BT group was 90 months and that of the RP group was 94 months. No significant differences in bPFS or cause-specific survival were observed between the 2 groups. The OS of the RP group was significantly higher than that of the BP group (P=0.030). Among the patients with a prostate volume >35 mL, those who underwent BT had significantly higher pPFS than those who underwent RP (P=0.041). In the localized prostate cancer, BT and RP offered similar oncological control in the localized prostate cancer. Stage T3 prostate cancer who undergo BT was associated with worse biochemical failure and was the only variable significantly predictive of biochemical recurrence.

Neoadjuvant Chemohormonal Therapy before Radical Prostatectomy for Japanese Patients with High-Risk Localized Prostate Cancer.

Background: Radical prostatectomy (RP) is the standard treatment in patients with high-risk prostate cancer (PCa). However, there is a high rate of recurrence, and new approaches are required to improve surgical efficacy. Here, we evaluated the feasibility and safety of neoadjuvant chemohormonal therapy (NCHT) before RP for Japanese patients with high-risk localized prostate cancer (PCa). Methods: From February 2009 to April 2016, 21 high-risk patients were enrolled in this prospective study. Patients were treated with docetaxel (70 mg/m2) every four weeks for three cycles and luteinizing hormone-releasing hormone agonist. Patients with grade 3–4 toxicities had 25% dose reductions for the following course. Results: Median follow-up was 88.6 months. The dose of docetaxel was reduced in 13 patients. The estimated five-year biochemical progression-free survival (bPFS) rate was 57.1%. National Comprehensive Cancer Network criteria (high-risk, but not very high-risk (nVHR) versus VHR) was associated with bPFS (p = 0.03). Five-year bPFS rates in the nVHR and VHR groups were 76.9% and 25.0%, respectively. There was a significant difference in bPFS between the nVHR and VHR groups (p = 0.023) by Kaplan–Meier analysis. Conclusions: Although our study included a small number of cases, at least in our exploration, NCHT was safe and feasible. However, more extensive treatment modalities are needed to improve outcomes, especially in VHR patients.

Low-/high-dose-rate brachytherapy boost in patients with intermediate-risk prostate cancer treated with radiotherapy: long-term results from a single institution team experience.

PurposeTo compare brachytherapy (BT) boost of low-dose-rate (LDR) and high-dose-rate (HDR) techniques in patients diagnosed with intermediate-risk prostate cancer.Material and methodsBetween January 2005 and February 2018, 142 patients (50 LDR and 92 HDR) with intermediate-risk prostate cancer were treated with a BT boost, and retrospectively analyzed. Prescribed dose was 45 Gy with external beam radiotherapy (EBRT) plus 100-108 Gy with LDR-BT, and 60 Gy with EBRT plus one fraction of 10 Gy with HDR-BT. 99% of patients received androgen deprivation therapy (ADT) for 6 months. Primary endpoint was to compare LDR and HDR boosts in terms of biochemical progression-free survival (bPFS). Secondary endpoint, after re-classifying patients into “favorable” and “unfavorable” sub-groups, was to analyze differences with a similar treatment intensity.ResultsMedian overall follow-up for the total cohort was 66.5 months (range, 16-185 months). There were no significant differences in bPFS, overall survival, cause specific survival, local failure, lymph node failure, or distant failure when LDR or HDR was employed. bPFS at 90 months was 100% for favorable, and 89% and 85% for unfavorable patients at 60 months and 90 months, respectively (log-rank test, p = 0.017). The crude incidence of genitourinary acute and chronic toxicity grade 3 was 0.7% and 4%, respectively. Twelve patients (8%) had chronic rectal hemorrhage grade 2, in whom argon was applied (4 LDR and 8 HDR).ConclusionsCombined treatment is an excellent therapeutic option in patients with intermediate-risk prostate carcinoma, with similar results in both LDR and HDR approaches and very low toxicities. Importantly, the current literature has indicated that unfavorable-risk patients belong to a different category, and should be treated as patients with high-risk factors. Therefore, the stratification and identification of both risk groups is extremely relevant.

Outcomes of Initial Therapy for Synchronous Brain Metastases from Extensive Stage Small Cell Lung Cancer

Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. 20% of SCLC patients have synchronous brain metastases at initial diagnosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases treated with chemotherapy (chemo) and/or whole brain radiation (WBRT). Among the 836 SCLC patients treated at a single institution between 1998 and 2018, 109 patients with synchronous brain metastases at initial diagnosis were included in this retrospective analysis. Survival was estimated with the Kaplan-Meier method. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression modeling and log-rank testing. Of the 109 patients, 18 received chemo without WBRT, 15 received WBRT without chemo, and 76 received chemo and WBRT. Of the 76 patients who received chemo and WBRT, 8 started both concurrently, 35 received chemo first, and 33 received WBRT first. Median WBRT dose was 30 Gy in 10 fractions. The median number of brain lesions at diagnosis was 3, and the median size of the largest metastasis was 2.0 cm. Median OS for the entire cohort was 9 months and median bPFS was 8.4 months. OS was 30.3% at 1 year and 14.4% at 2 years. Increased number of brain lesions was significantly associated with decreased OS. 59 patients presented with neurological symptoms, which was not associated with OS or bPFS. 46 patients had isolated brain metastases (no extracranial metastases), which was not associated with improved OS (p = 0.061) or bPFS (p = 0.17) compared to patients with other extracranial metastatic disease. The median age at diagnosis was 63. Patients younger than 63 years old had improved OS compared to patients age 63 or older, but not bPFS. Patients who received chemo and WBRT had improved OS compared to those who had either chemo or WBRT alone (p<0.001), but there was no difference in bPFS (p = 0.34). There was no significant difference in OS or bPFS depending on the sequence of therapy initiation. For patients who had chemo followed by WBRT, the median time between start of chemo and start of radiation was 103 days (range 6 – 182 days), which was not significantly associated with OS or bPFS. 13 patients received upfront brain metastasis resection, which was associated with improved OS but not bPFS compared to those who did not have surgery. 14 patients received SRS or partial brain radiation as part of their initial therapy, which was not significantly associated with OS or bPFS. 15 patients received salvage brain radiation after WBRT failure, which was associated with improved OS compared to those who did not have salvage radiation (25.5 months vs 8.0 months, p<0.001). The combination of chemo and WBRT was associated with improved OS compared to either modality alone. The sequence of treatment was not associated with OS or bPFS. Shorter time to WBRT after chemo was not significantly associated with OS or bPFS.

Abiraterone acetate plus Prednisone/Prednisolone compared with Enzalutamide in metastatic castration resistant prostate cancer before or after chemotherapy: A retrospective study of real-world data (ACES).

BackgroundAbiraterone acetate combined with Prednisone/Prednisolone (AA+P) and Enzalutamide (ENZ) have proven survival benefit in men with metastatic castration‐resistant prostate cancer (mCRPC) in chemotherapy‐naïve and prior chemotherapy patients. There have been no studies directly comparing the effectiveness of ENZ to AA+P in mCRPC patients.MethodsA retrospective, survival analysis study of 143 real‐world mCRPC patients (90 in AA+P and 53 in ENZ group) was conducted. Patients who started their treatment between February 2012 and May 2016 were included. The primary end point was biochemical progression‐free survival (bPFS). Secondary end points were radiological progression‐free survival (rPFS) and overall survival (OS). Toxicity data were also collected. Data were analyzed using Cox proportional hazards (PH) models, adjusting for covariates: prior radical treatment; Gleason score; prostate‐specific antigen; age; and chemotherapy naïve or not.ResultsAfter median follow‐up of 15 months (interquartile range 7 to 23), 112 events of biochemical progression were observed (71 in AA+P and 41 in ENZ). About 41% in AA+P group and 30% patients in ENZ group received prior chemotherapy. The chance of biochemical progression was significantly lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.35 to 0.82, P = .004). There was a trend implying the chance of rPFS could be higher among ENZ patients than AA+P patients (HR 1.24, 95% CI 0.76 to 2.02, P = .4). There is no difference in OS between ENZ and AA+P patients, when adjusting for all covariates in the Cox PH model (HR 0.91, 95% CI 0.59 to 1.41, P = .7). About 38% of ENZ patients reported fatigue compared to 16% of AA+P patients, while hypertension was reported slightly more in AA+P patients.ConclusionsThis study showed a statistically significant difference in bPFS, favoring ENZ, but no significant difference in rPFS or OS.

External Beam Radiation Therapy (EBRT) and High-Dose-Rate (HDR) Brachytherapy for Intermediate and High-Risk Prostate Cancer: The Impact of EBRT Volume

Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site. A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive. Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed. A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity.

Quality of Life, Treatment Toxicity, and Biochemical Control in Patients Treated with Dose-Escalation Brachytherapy and EBRT for Intermediate- and High-Risk Prostate Cancer

The use of prostate brachytherapy (BT) as a dose-escalation technique in conjunction with external beam radiation therapy (EBRT) is associated with improved biochemical progression-free survival (b-PFS). This technique is also associated with increased genitourinary (GU) and gastrointestinal (GI) toxicity. This study compared b-PFS and post-treatment toxicity in patients receiving either EBRT-BT or EBRT alone. We hypothesized that patients in the EBRT-BT cohort would demonstrate improved b-PFS and an increased incidence of GU and GI toxicity. The start date of radiation was taken as t-0 to determine acute (<6 months) and late (>6 months) events. Incidence of acute and late GU and GI toxicity was obtained along with the prevalence of late toxicity 12-23 months after treatment and ≥ 24 months after treatment. Mann-Whitney U tests were used to compare cohort differences. 96 patients met inclusion criteria for the EBRT-BT cohort with median follow-up of 26.0 months. 27 patients met inclusion for the EBRT cohort with median follow-up of 11.6 months. Log-rank comparison of the b-PFS rates between the EBRT cohort (n=21, 95.2%) and the EBRT-BT cohort (n=71, 95.8%) was not significant (p = .484). Patients in the EBRT-BT cohort demonstrated a higher incidence of moderate (CTCAE v4 grade 2 or higher) GU toxicity at follow-up ≥ 6 months after treatment compared to the EBRT group (37.1% vs 9.1%, p = .091). In contrast, acute moderate GU toxicity was similar in both EBRT-BT and EBRT cohorts (48.9% vs 57.7%, p = .647). Comparison of toxicity incidence in our study approached significance in patients seen for follow-up ≥ 6 months post-treatment. In contrast, the ASCENDE-RT trial reported significantly higher acute moderate GU toxicity in the EBRT-BT treatment group (Rodda Int J Radiation Oncol Biol Phys 2017). Furthermore, our study reports no significant difference in b-PFS between the two treatment cohorts. While other studies have shown improved b-PFS in patients receiving EBRT-BT, these distinctions were noted more than 4 years (Morris Int J Radiation Oncol Biol Phys 2017) and 5 years (Sathya J Clin Oncol 2005) after the end of treatment. Thus, longer follow-up is warranted for more reliable comparison.

Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial

PurposeTo compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL). Methods and MaterialsAndrogen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL. ResultsCompared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319). ConclusionsReplacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.

External beam radiotherapy (EBRT) and high dose rate (HDR) brachytherapy for intermediate and high-risk prostate cancer: Whole pelvis or prostate-only EBRT?

86 Background: In high-risk prostate cancer, the risk of occult lymph node metastases in the pelvic lymph nodes can be as high as 40%. However, the use of whole pelvis radiotherapy (WPRT) in high-risk patients remains controversial with mixed retrospective evidence and two negative prospective trials. Data from a national UK database of patients treated with external-beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy was reviewed to evaluate the benefit of pelvic treatment. Methods: From 2009 to 2013, 755 patients with intermediate- and high-risk prostate cancer (clinical stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen (pPSA) ≥10) were treated with EBRT and HDR brachytherapy. The pelvic nodes to the level of the common iliac chain were treated in 370 patients with a dose of 46Gy in 23 fractions. The remaining 385 patients received radiotherapy to the prostate only (PORT) at a dose of 37.5Gy in 15 fractions. A single dose of 15Gy was delivered with HDR brachytherapy in each case. Corresponding biologic effective doses to the prostate were 107Gy and 100Gy respectively (α/β = 1.5). 96.5% of patients received ADT with a median duration of 24 months. Biochemical failure was defined as a PSA rise of ≥2ng/ml above nadir. Analysis used log-rank and Cox univariate and multivariate tests. Results: Median follow-up was 4.5 years; 5-year biochemical progression-free survival rates for the WPRT versus the PORT arms were 88% vs 80% (p &lt; 0.05) for all patients and 89% vs 76% (p &lt; 0.05) for high-risk patients. Differences in bPFS remained significant (p &lt; 0.05) after accounting for Gleason score, pPSA, T stage and ADT duration as co-variates. There was no difference in overall survival. Conclusions: Whole pelvis EBRT with HDR brachytherapy appears to significantly improves 5-year biochemical progression-free survival in intermediate- and high-risk prostate cancer compared to prostate-only EBRT and HDR brachytherapy which persists after allowing for covariates including presenting tumour parameters and ADT use. The PIVOTAL boost trial in the UK will assess this further in a prospective randomised study.

Ultra-Low Risk Prostate Cancer Treated with Cryotherapy versus Radiation Therapy

Cryotherapy and radiation therapy are definitive local treatment approaches for prostate cancer. There is both prospective and retrospective data for definitive radiotherapy, but the use of cryotherapy has been limited primarily to single arm single institutional retrospective studies. The American Urological Association asserts that definitive cryotherapy has a role in low risk disease. Per the NCCN guidelines, ultra-low risk prostate cancer patients are candidates for active surveillance as a viable monitoring approach, but some of these patients insist on proceeding with definitive therapy. We undertook a retrospective analysis of the most favorable subset of prostate cancer patients, with ultra-low risk disease, to comparatively elucidate the utility of radiotherapy and cryotherapy. Institutional Review Board approval was obtained prior to conducting a retrospective chart review of patients treated at our institution from 1999-2014 with external beam radiation therapy (EBRT), low dose rate brachytherapy (LDR), and cryotherapy. Patients meeting inclusion criteria for the present study were diagnosed with prostate cancer and had ultra-low-risk disease as defined by all of the following conditions: stage T1c TNM classification, PSA < 10, and a combined Gleason score of 3+3, 1-3 cores positive with no more than 50% of an individual core involved by tumor. Only patients who received definitive LDR, EBRT or cryotherapy monotherapy were included in the analysis. We excluded patients who were treated with radiation for surgical salvage. Disease specifics and failure details were collected for all patients. Failure was defined as PSA nadir +2ng/mL Sixty-five patients were treated with radiation (39 with EBRT and 26 with LDR), while 40 patients were treated with cryotherapy, The EBRT dose median was 75Gy (range: 72.0-79.2Gy). LDR patients were treated with 120Gy Pd-103 or 140-145Gy I-125 implant. All cryotherapy patients were treated with 2 freeze and thaw cycles. Median cores positive were 1 (range 1-3). Ninety percent of men had unilateral disease with 10% having bilateral disease. A median of 10% maximum volume of cores were positive (range: 1-50%). Mean PSA density was 0.11ng/mL/gm (range 0.09-0.14). Mean PSA follow-up was 57.3 and 51.5 months in the radiotherapy and cryotherapy groups respectively. Eighty-nine percent (58/65) and only 67.5% (13/40) of the cryotherapy patients were free of biochemical progression (p=0.0125). There was no difference in bPFS between EBRT an LDR (p=1.0). Time to biochemical progression in failed patients was 62 months in the radiotherapy group and 11 months in the cryotherapy group. In our practice, patients undergoing definitive treatment for ultra-low risk prostate cancer appear to do better with radiation therapy than cryotherapy. We likewise do not recommend cryotherapy as definitive treatment upfront for prostate cancer.

Five-Year Biochemical Progression-Free Survival Following Salvage Whole-Gland Prostate Cryoablation: Defining Success with Nadir Prostate-Specific Antigen.

Salvage prostate cryoablation is an effective treatment for patients with localized prostate cancer relapse following primary radiotherapy. The postsalvage prostate-specific antigen (PSA) nadir that best predicts long-term biochemical progression-free survival (bPFS) is not yet defined. We sought to determine what nadir PSA best predicted success following salvage whole-gland cryoablation. We retrospectively reviewed a cohort of 486 hormone-naive patients who underwent salvage whole-gland cryoablation from the Cryo On-Line Database (COLD). Studied variables were age, race, initial PSA, presalvage prostate-specific antigen (psPSA), initial Gleason score, Gleason score at presalvage biopsy, clinical stage, and follow-up PSA values. Kaplan-Meier (KM) analysis was used to calculate 5-year bPFS using the Phoenix criteria. Hazard ratio and relative risk were also analyzed. Differences among the KM estimates, at 5 years, were calculated using the log-rank test. Using group thresholds, KM analysis identified nadir PSA less than or greater than 0.4 ng/mL as the nadir PSA threshold, with the greatest difference in bPFS. The KM estimated 5-year bPFS was 75.5% and 22.1% for nadir PSA <0.4 and ≥0.4 ng/mL, respectively. Stratified by psPSA, the KM estimated 5-year bPFS comparing patients with PSA nadir <0.4 vs ≥0.4 ng/mL was 78.5% and 17.9% (p < 0.0001) for psPSA <4 ng/mL, 77.1% and 15.7% (p < 0.0001) for psPSA 4-10 ng/mL, and 77.8% and 16.8% (p < 0.0001) for psPSA >10 ng/mL, respectively. The best objective indicator of biochemical success following whole-gland salvage cryoablation of the prostate is PSA nadir <0.4 ng/mL.

Long-term Outcomes for Clinically Localized Prostate Cancer Treated With Permanent Prostate Brachytherapy With Pd-103

In view of the prolonged natural history of prostate cancer, long-term follow-up is warranted to determine the efficacy of treatment. We evaluated the outcome of our prostate brachytherapy patients that were treated at least 15 years ago. The study included 118 consecutive cases of prostate cancer treated with permanent prostate brachytherapy with Pd-103 by a single radiation oncologist between August 1997 and September 1999. Mean age of patients was 73 years (range 53-86 years). Mean prostate-specific antigen (PSA) was 9.25 ng/mL (range 1.3-73.88 ng/mL). The median Gleason score was 6 (range 3-8). Among T stage, 106 (90%) patients had ≤T2a, 10 (8.4%) had T2b, and 2 (1.6%) had T2c or higher disease. Unilateral disease was present in 81 (70%), and 35 (30%) had bilateral disease. The numbers of low-risk, intermediate-risk, and high-risk prostate cancer cases were 62 (52.5%), 44 (37.2%) and 12 (10.1), respectively. Brachytherapy as monotherapy was done in 100 (85%) patients, while 18 (15%) received supplemental external beam radiation therapy (EBRT) to a dose of 45 Gy delivered in 1.8-Gy fractions. Androgen deprivation therapy was used in 75 (64%) patients, mostly for less than 4 months, before the implant. For monotherapeutic approach with brachytherapy, the minimum peripheral dose with Pd-103 was 125 Gy and 90 Gy with boost brachytherapy. Patients were monitored by physical examination, including digital rectal examination and serum PSA determination at 3-6 month intervals for first 5 years and then on a yearly basis. All patients were assessed for clinical and biochemical recurrence based on the Phoenix definition. Kaplan-Meier analysis and curves were used to determine the cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS). Follow-up ranged from 1 to 17 years with a median overall follow-up of 14 years and biochemical follow-up of 13 years for patients who are still alive. Overall median and biochemical follow-up was 11 years and 8 years respectively. A total of 29 cases had biochemical recurrence, with a biochemical control rate of 75%. Distant metastatic disease was documented in 3 patients. The 15-year bPFS for the entire cohort was 68%. The 15-year bPFS by risk group stratification was 75%, 61%, and 52% for low-, intermediate-, and high-risk patients, respectively. There was significant difference in bPFS between low-, intermediate-, and high-risk groups. The prostate cancer-specific survival rate was 97% at 15 years. The overall survival reached 50% at 15 years. Our long-term experience with Pd-103 based permanent prostate brachytherapy shows excellent efficacy as assessed by the 15-year cancer-specific and biochemical relapse-free survival.

Effect of germ-line BRCA mutations in biochemical relapse and survival after treatment for localized prostate cancer.

29 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter cause-specific survival (CSS). Germline BRCA mutations are associated with worse PrCa outcomes. In this study, we analyzed biochemical-progression free survival (bPFS) after conventional treatments for localized PCa in a cohort of BRCA patients from the UK. Currently, BRCA1/2 carriers are treated with the same protocols used for non-carriers. Methods: In this retrospective case-control study, each BRCA carrier (10 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by: age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment (RT or RP), androgen-deprivation therapy (ADT) and year of treatment (±5yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 176 patients (pts) were included. Median follow-up was 97 months (ms). Median age at diagnosis was 58.5 yrs (43-75). 80 pts received RT (16 BRCA2, 4 BRCA1, 60 NC) and 85% also received ADT≥6 ms. 96pts underwent RP (18 BRCA2, 6 BRCA1 and 72 NC). Following RT treatment, 5yrs-CSS was 96% in NC and 47% in BRCA carriers (p=2x10-5), whilst no difference was seen after RP (5yrs-CSS was 98.5% in NC vs 93.3% in BRCA). Five-years bFPFS after RT was 74% in NC and 24% in BRCA (p=0.002). No difference was observed in 5yrs-bPFS between BRCA carriers and NC treated with RP (52% vs 66% , p=0.346). The adjusted MVA (including tumour stage, local treatment, ADT and BRCA status) confirmed the independent prognostic value of BRCA status for bPFS and CSS. Among BRCA carriers, the independent risk was greater when the analysis was limited to BRCA2 pts . Conclusions: Our results suggest that BRCA carriers have worse local disease control than NC when conventionally treated with RT. No differences in bPFS were observed in pts treated with RP after &gt;8 yrs median follow-up. These results may have implications for tailoring clinical management in these patients.

BRCA carrier status as an independent prognostic factor associated with earlier biochemical relapse in local prostate cancer.

1545 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter survival. Germline BRCA mutations are associated with worse PCa outcomes. BRCA carriers are currently treated with the same protocols used for non-carriers. We analyzed biochemical-progression free survival (bPFS) after conventional treatment for localized PCa in a cohort of BRCA patients (pts). Methods: In this retrospective case-control study, each BRCA carrier (9 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment , androgen-deprivation therapy (ADT) and year of treatment (±3 yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 172 pts were included. Median follow-up was 76 months (ms). Median age at diagnosis was 58 yrs (43-75). Tumour stages were I 11%, IIA 19%, IIB 28%, III 28%, IV 14%. 80 pts received RT (18 BRCA2, 5 BRCA1, 57NC) and 85% also received ADT (70% for ≥6 months). 92 pts underwent RP (16 BRCA2, 4 BRCA1 and 72 NC), and 9% of them received ADT (&lt;6months). Overall, median bPFS was 71ms. For those treated with RT, median bPFS was 65ms in NC vs 39ms in BRCA carriers (p=0.023). bPFS was not affected by ADT duration. Median bPFS after RP was 65ms in BRCA carriers. No difference was observed in 3yrs-bPFS between BRCA carriers and NC (73% vs 76%). The adjusted MVA confirmed the independent prognostic value of tumour stage (p=0.004) and BRCA status (p=0.032) for bPFS. Among BRCA carriers, the risk was greater when the analysis was limited to BRCA2 pts (p=0.013, HR 2.1,.95%CI 1.2-3.7). Conclusions: Our results suggest that BRCA carriers with PCa have worse local disease control than NC when treated with RT, regardless of ADT duration. No differences in bPFS were observed in pts treated with RP after &gt;6 yrs median follow-up. These results may have implications for tailoring clinical management for these patients.

20 Gy Versus 44 Gy of Supplemental External Beam Radiotherapy With Palladium-103 for Patients With Greater Risk Disease: Results of a Prospective Randomized Trial

The necessity of external beam radiotherapy (EBRT) as a supplement to prostate brachytherapy remains unknown. We report brachytherapy outcomes for patients with higher risk features randomized to substantially different supplemental EBRT regimens. Between December 1999 and June 2004, 247 patients were randomized to 20 Gy vs. 44 Gy EBRT followed by a palladium-103 boost (115 Gy vs. 90 Gy). The eligibility criteria included clinically organ-confined disease with Gleason score 7-10 and/or pretreatment prostate-specific antigen (PSA) level 10-20 ng/mL. The median follow-up period was 9.0 years. Biochemical progression-free survival (bPFS) was defined as a PSA level of ≤0.40 ng/mL after nadir. The median day 0 prescribed dose covering 90% of the target volume was 125.7%; 80 men received androgen deprivation therapy (median, 4 months). Multiple parameters were evaluated for their effect on bPFS. For the entire cohort, the cause-specific survival, bPFS, and overall survival rates were 97.7%, 93.2%, and 80.8% at 8 years and 96.9%, 93.2%, and 75.4% at 10 years, respectively. The bPFS rate was 93.1% and 93.4% for the 20-Gy and 44-Gy arms, respectively (p = .994). However, no statistically significant differences were found in cause-specific survival or overall survival were identified. When stratified by PSA level of ≤10 ng/mL vs. >10 ng/mL, Gleason score, or androgen deprivation therapy, no statistically significant differences in bPFS were discerned between the two EBRT regimens. On multivariate analysis, bPFS was most closely related to the preimplant PSA and clinical stage. For patients with biochemically controlled disease, the median PSA level was <0.02 ng/mL. The results of the present trial strongly suggest that two markedly different supplemental EBRT regimens result in equivalent cause-specific survival, bPFS, and overall survival. It is probable that the lack of benefit for a higher supplemental EBRT dose is the result of the high-quality brachytherapy dose distributions.

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient. Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

Androgen deprivation therapy does not impact cause-specific or overall survival in high-risk prostate cancer treated with brachytherapy and supplemental external beam

15578 Background: To determine cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) in high risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods: From April 1995 through July 2002, 204 patients with high risk prostate cancer (Gleason score = 8 and/or PSA &gt; 20 ng/mL and/or clinical stage = T2c) underwent brachytherapy with or without supplemental therapies. Of the 204 patients, 193 (94.6%) received supplemental XRT and 119 (58.3%) received ADT (ADT = 6 months n=40 and ADT &gt; 6 months n = 79). Median follow-up was 7.0 years. All patients were implanted at least 4 years prior to analysis. BPFS was defined by a PSA = 0.40 ng/mL after nadir. Multiple clinical, treatment and dosimetric parameters were evaluated for the impact on survival. Results: The ten-year CSS, bPFS and OS were 88.9%, 86.6% and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naïve, ADT = 6 months and ADT &gt; 6 month cohorts (79.7% vs. 95.0% vs. 89.9%, p= 0.032). ADT did not impact CSS (94.0% vs. 87.1%, p=0.983 ) or OS (65.2% vs. 70.3%, p = 0.713). For bPFS patients, the median post-treatment PSA was &lt; 0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent positive biopsies and duration of ADT best predicted for bPFS. OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died with 26 of the deaths due to cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: Androgen deprivation therapy improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact overall survival. No significant financial relationships to disclose.

Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score > or = 8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage > or = T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA < or = 0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT < or = 6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS.