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Purpose: To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS)., Methods and Materials: Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS)., Results: The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of ≥ 80 significantly influenced OS (median OS, 4.8 months for KPS ≤ 70 vs. 8.8 months for KPS ≥ 80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of ≤ 70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157)., Conclusions: Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with metastatic cancer, especially for patients previously treated with WBRT. A KPS of ≥ 80 predicts for an improved outcome., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose of this study is to determine the types, incidence, and severity of acute complications of intracranial stereotactic radiosurgery (SRS), specifically Gamma Knife (GK). Patients who had never had previous SRS were eligible for this prospective IRB-approved study. The questionnaire used applicable questions from CTCAE v.3.0, the Brief Pain Questionnaire (Short Form), Brief Fatigue Inventory, and the Tinnitus Handicap Inventory. Questionnaires were obtained prior to Gamma Knife (GK), 1 week, 1 month, and 2 months to assess complications. Seventy-six eligible patients (median age of 62 years) had complete data and were analyzed. Diagnoses included: 26 (34%) with brain metastases, 15 (20%) with trigeminal neuralgia, 12 (16%) with schwannoma, 10 (13%) with meningioma, 7 (9%) with arteriovenous malformation, 3 (4%) with pituitary adenoma, and 3 (4%) with other. At 1 week, 24% developed minimal scalp numbness (p =0.0004 baseline compared to 1 week). Only 13% had minimal scalp numbness at 1 month and 2% at 2 months (both p=NS compared to baseline). There was no difference in scalp tingling between baseline and the various time points. Thirteen percent developed pin site pain at 1 week with a median intensity level of 2 out of 10. By one month, only 3% had pin site pain with a median intensity level of 3 out of 10. Four percent developed pin-site infection at 1 week and none at 1 and 2 months. There was no significant difference in nausea from baseline at 1 week, but there was worsening nausea at 1 month (p =0.0114). By 1 month, 10% reported new local hair loss. 23%, 16%, and 15% complained of new/worsening fatigue at 1 week, 1 month, and 2 months, respectively, but 40% reported fatigue at baseline. Balance improved following SRS over all time periods (for all comparisons, p <0.009). 1%, 6%, and 3% developed new tinnitus at 1 week, 1 month, and 2 months, respectively, which was significant when comparing baseline to non-baseline (p =0.0269). Thirty-two patients were employed prior to SRS. Three (9%) patients did not return to work. Twenty-seven (84%) patients returned to work a median of 4 days after SRS. Two people did not report their employment status after SRS. There was no significant difference in face swelling, headache, eye pain, vomiting, seizures, or passing out at any intervals compared to baseline. This prospective study demonstrates that GK is well tolerated with few patients developing major acute effects. Many patients are able to return to work shortly after GK.

Background: Accurate preoperative and postoperative risk assessment has been critical for counseling patients regarding radical prostatectomy for clinically localized prostate cancer. In addition to other treatment modalities, neoadjuvant or adjuvant therapies have been considered. The growing literature suggested that the experience of the surgeon may affect the risk of prostate cancer recurrence. The purpose of this study was to develop and internally validate nomograms to predict the probability of recurrence, both preoperatively and postoperatively, with adjustment for standard parameters plus surgeon experience., Methods: The study cohort included 7,724 eligible prostate cancer patients treated with radical prostatectomy by 1 of 72 surgeons. For each patient, surgeon experience was coded as the total number of cases conducted by the surgeon before the patient's operation. Multivariable Cox proportional hazards regression models were developed to predict recurrence. Discrimination and calibration of the models was assessed following bootstrapping methods, and the models were presented as nomograms., Results: In this combined series, the 10-year probability of recurrence was 23.9%. The nomograms were quite discriminating (preoperative concordance index, 0.767; postoperative concordance index, 0.812). Calibration appeared to be very good for each. Surgeon experience seemed to have a quite modest effect, especially postoperatively., Conclusions: Nomograms have been developed that consider the surgeon's experience as a predictor. The tools appeared to predict reasonably well but were somewhat little improved with the addition of surgeon experience as a predictor variable., ((c) 2009 American Cancer Society.)

The independent prognostic importance of microscopic bladder neck involvement by prostate cancer in radical prostatectomy is questionable. We studied a cohort of 1845 patients to determine the significance of microscopic bladder neck involvement. Bladder neck involvement was defined as prostate cancer present within the coned bladder neck. We further categorized the cases as 'true bladder neck involvement' and 'false bladder neck involvement.' True bladder neck involvement required prostate cancer within thick smooth muscle bundles without intermixed benign prostatic glands. False bladder neck involvement was characterized by prostate cancer intermixed with benign prostatic glands. Bladder neck involvement was analyzed in relation to preoperative serum prostate-specific antigen (PSA) level, extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, radical prostatectomy Gleason score, and tumor volume. Of the 90 patients (4.9%) with microscopic bladder neck involvement, 63 were further classified as true bladder neck involvement and 27 as false bladder neck involvement. In univariate model, both types of bladder neck involvement (P<0.001), true (P<0.001), and false (P=0.040), were significantly associated with increased PSA-recurrence risk compared to bladder neck negative cases. In multivariate model the PSA-recurrence relative risk associated with bladder neck involvement (true or false) was not a significant independent prognostic factor. Extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, PSA, and Gleason score were significant independent predictors of PSA recurrence. The time to biochemical recurrence in patients with bladder neck involvement was similar to that of pT2 with positive surgical margin or pT3a with negative surgical margin patients (Kaplan-Meier curves). Bladder neck involvement was associated with other adverse pathologic features, but was not an independent predictor of PSA recurrence. In view of the previous and current data, the staging system for bladder neck involvement should be revised and patients may be best categorized as having pT3a disease.

Purpose: Accurate categorization of high risk prostate cancer cases remains elusive. Various schemes based on clincopathological criteria have been proposed to stratify cases by presumed recurrence risk. We determined whether survival outcomes are dependent on the specific definition., Materials and Methods: The study population included men who underwent radical prostatectomy from 1987 to 1995 (708) and 1996 to 2007 (3,351). Patients who received adjuvant therapy or had no postoperative prostate specific antigen were excluded from analysis. High risk patients were identified based on 6 commonly used definitions. Biochemical failure was defined as a prostate specific antigen of 0.4 ng/ml or greater and increasing or initiation of salvage therapy. Estimates of biochemical relapse-free survival were generated with the Kaplan-Meier method. Hazard ratios for disease recurrence were estimated using Cox proportional hazards analysis., Results: High risk patients determined by the 6 definitions demonstrated a 2.7 to 5.3-fold increased hazard of biochemical relapse, and 5 and 10-year biochemical relapse-free survival rates were 36% to 58% and 25% to 43%, respectively. When stratified by date of treatment high risk patients from 1987 to 1995 generally had worse biochemical relapse-free survival compared to those treated after 1996. Within each era the variation in biochemical relapse-free survival among various high risk definitions was not substantial., Conclusions: Biochemical relapse-free survival after radical prostatectomy does not vary substantially based on the specific definition of high risk prostate cancer. There is a trend toward improved biochemical relapse-free survival in patients treated more recently, perhaps reflecting stage migration or changes in surgical technique. The data suggest that high risk prostate cancer may represent a relatively homogeneous population.

Background: The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole-brain radiation therapy (WBRT)., Methods: The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed., Results: The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence < or = 6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty-eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose <22 grays and lesion size >2 cm were found to be predictive of local failure., Conclusions: In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS., ((c) 2008 American Cancer Society.)

Purpose: The Partin tables were updated in 2007. However, to our knowledge their accuracy and performance characteristics have not been confirmed in an external validation cohort., Materials and Methods: We examined the discrimination and calibration properties of the 2007 Partin tables in 1,838 men treated with radical prostatectomy between 2001 and 2005 at Cleveland Clinic Foundation. The ROC derived AUC and the Brier score were used to quantify the discriminant properties of the predictions of the 2007 Partin tables for extraprostatic extension, seminal vesical invasion and lymph node invasion. Loess based calibration plots were used to examine the relationship between the predicted and observed rates of extraprostatic extension, seminal vesical invasion and lymph node invasion., Results: The rates of extraprostatic extension, seminal vesical invasion and lymph node invasion were 26.9%, 5.5% and 1.8%. The accuracy of extraprostatic extension, seminal vesical invasion and lymph node invasion prediction was 71%, 80% and 75% according to the AUC method, and 0.176, 0.051 and 0.037 according to the Brier score, respectively. Extraprostatic extension predictions between 0% and 25%, and lymph node invasion predictions between 0% and 5% correlated well with observed extraprostatic extension and lymph node invasion rates, respectively. Conversely a suboptimal correlation was recorded between predicted and observed seminal vesical invasion rates as well as between predicted and observed rates of extraprostatic extension and lymph node invasion for predicted extraprostatic extension and lymph node invasion values above 25% and 5%, respectively., Conclusions: In this examined validation cohort the overall accuracy (AUC) of the Partin tables was comparable to results reported in the original 2007 development cohort. However, performance characteristics indicate that predictions within specific probability ranges should be interpreted with caution.

Objectives: We previously demonstrated that there is a learning curve for open radical prostatectomy. We sought to determine whether the effects of the learning curve are modified by pathologic stage., Methods: The study included 7765 eligible prostate cancer patients treated with open radical prostatectomy by one of 72 surgeons. Surgeon experience was coded as the total number of radical prostatectomies conducted by the surgeon prior to a patient's surgery. Multivariable regression models of survival time were used to evaluate the association between surgeon experience and biochemical recurrence, with adjustment for PSA, stage, and grade. Analyses were conducted separately for patients with organ-confined and locally advanced disease., Results: Five-year recurrence-free probability for patients with organ-confined disease approached 100% for the most experienced surgeons. Conversely, the learning curve for patients with locally advanced disease reached a plateau at approximately 70%, suggesting that about a third of these patients cannot be cured by surgery alone., Conclusions: Excellent rates of cancer control for patients with organ-confined disease treated by the most experienced surgeons suggest that the primary reason such patients recur is inadequate surgical technique.

Objectives: To evaluate the presentation, location and overall survival of pelvic recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder., Patients and Methods: We reviewed a consecutive series of 130 patients who had a limited bilateral pelvic lymph node dissection (PLND) and RC between 1987 and 2000, and who later developed pelvic recurrence. All patients were staged N0M0 before RC and no patient received neoadjuvant radio/chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and the bifurcation of iliac vessels to the circumflex iliac vein. Pelvic recurrence was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Kaplan-Meier and Cox proportional hazards analyses were used to determine if imaging or symptomatic presentation, age, pT stage, and pN status were predictive of overall survival., Results: The median (range) time from RC to pelvic recurrence was 7.3 (1.2-55.4) months. No patients had concomitant distant metastasis. Of the patients, 61.5% were diagnosed with pelvic recurrence because of symptoms, and 38.5% by surveillance computed tomography (CT). Of the 130 patients, 128 died, with a median survival from the time of pelvic recurrence of 4.9 (0.1-129.3) months. The median overall survival time for pelvic recurrence diagnosed with CT was 21.6 months, vs 10.6 months for symptomatic presentations (P < 0.001). In the uni- and multivariate models, type of presentation (CT vs symptomatic) and pT stage were predictors of overall survival, while age and pN status were not., Conclusion: The prognosis of patients with pelvic recurrence after RC for TCC is poor even with subsequent therapy, emphasizing the need for optimum local control at the time of initial treatment.

Background: Men who undergo radical prostatectomy (RP) are at long-term risk of biochemical recurrence (BCR). In this report, the authors have described a model capable of predicting BCR up to at least 15 years after RP that can adjust predictions according to the disease-free interval., Methods: Cox regression was used to model the probability of BCR (a prostate-specific antigen level>0.1 ng/mL and rising) in 601 men who underwent RP with a median follow-up of 11.4 years. The statistical significance of nomogram predictors was confirmed with a competing-risks regression model. The model was validated internally with 200 bootstraps and externally at 5 years, 10 years, and 15 years in 2 independent cohorts of 2963 and 3178 contemporary RP patients from 2 institutions., Results: The 5-year, 10-year, 15-year, and 20-year actuarial rates of BCR-free survival were 84.8%, 71.2%, 61.1%, and 58.6%, respectively. Pathologic stage, surgical margin status, pathologic Gleason sum, type of RP, and adjuvant radiotherapy represented independent predictors of BCR in both Cox and competing-risks regression models and constituted the nomogram predictor variables. In internal validation, the nomogram accuracy was 79.3%, 77.2%, 79.7%, and 80.6% at 5 years, 10 years, 15 years, and 20 years, respectively, after RP. In external validation, the nomogram was 77.4% accurate at 5 years in the first cohort and 77.9%, 79.4%, and 86.3% accurate at 5 years, 10 years, and 15 years, respectively, in the second cohort., Conclusions: Patients who undergo RP remain at risk of BCR beyond 10 years after RP. The nomogram described in this report distinguishes itself from other tools by its ability to accurately predict the conditional probability of BCR up to at least 15 years after surgery., (Copyright (c) 2008 American Cancer Society.)

Purpose: We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000., Materials and Methods: Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined., Results: The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series., Conclusions: Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

Purpose: A significant proportion of patients with prostate cancer with Gleason score 6 disease at biopsy is upgraded to Gleason score 7 or higher after radical prostatectomy, increasing the risk of adverse outcome. We identified clinical and pathological parameters that predict pathological upgrading in this population., Materials and Methods: A total of 268 patients with biopsy Gleason score 6 prostate cancer who underwent biopsy and radical prostatectomy between October 1999 and January 2007 were included in the study. Pretreatment characteristics were used to identify predictors of pathological upgrading. Upgrading significance was established by comparing radical prostatectomy pathology between cases that were and were not upgraded., Results: A total of 134 patients (50%) were upgraded postoperatively to Gleason score 7 or higher. Preoperative prostate specific antigen greater than 5.0 ng/ml (p = 0.036), prostate weight 60 gm or less (p = 0.004) and more cancer volume at biopsy, defined by cancer involving greater than 5% of the biopsy tissue (p = 0.002), greater than 1 biopsy core (p <0.001) or greater than 10% of any core (p = 0.014), were associated with pathological upgrading. Upgraded patients were more likely to have extraprostatic extension and positive surgical margins at radical prostatectomy (p <0.001 and 0.001, respectively)., Conclusions: Prostate specific antigen, prostate volume and biopsy cancer volume predict clinically significant upgrading in patients diagnosed with Gleason score 6 disease. These parameters may be valuable in the pretreatment risk assessment of this patient population.

Objectives: To compare the long-term differences in actuarial biochemical relapse-free survival rates from a contemporary series of patients who underwent radical prostatectomy with and without pelvic lymph node dissection (PLND)., Methods: The records of 806 consecutive radical prostatectomy cases performed from January 1995 to June 1999 were reviewed. The entire subset of patients (n = 336) with low-risk disease, defined by a prostate-specific antigen level of 10 ng/mL or less, biopsy Gleason score of 6 or less, and clinical Stage T1 or T2a, who had not received adjuvant or neoadjuvant therapy were divided into two groups according to whether PLND was performed (PLND group, n = 140) or omitted (no-PLND group, n = 196). A Cox proportional hazards model was used to analyze the effect of demographic, pretreatment, surgical, and pathologic factors on the likelihood of biochemical failure. Biochemical relapse-free survival for each group was estimated by Kaplan-Meier analysis. The median prostate-specific antigen follow-up time for the entire group was 89.0 months, with a similar follow-up for both cohorts (PLND group 94.5 months and no-PLND group 88.0 months, Mann-Whitney U test, P = 0.14)., Results: The long-term biochemical relapse-free survival rate for the entire cohort was 86.1% at 10 years. The 10-year actuarial biochemical relapse-free rate for the PLND and no-PLND groups was 83.8% and 87.9%, respectively (log-rank, P = 0.33). On univariate analysis, PLND was not an independent predictor of outcome (Wald, P = 0.33)., Conclusions: The results of our study have shown that the omission of limited PLND in patients with favorable tumor characteristics does not adversely affect biochemical relapse-free survival at 10 years. Such patients can be spared the morbidity and cost of PLND without affecting their chance for cure.

Background: Trigeminal neuralgia is a debilitating condition caused by compression of the trigeminal nerve, ganglions, or divisions. Gamma knife radiosurgery has been increasingly used in the treatment of trigeminal neuralgia as a non-invasive alternative to microvascular decompression and rhizotomies., Methods: We reviewed the medical literature regarding outcomes, time course, and prognostic factors for successful pain control in gamma knife radiosurgery. The dosimetry, target, complications of treatment, as well as perceived quality of life in treatment were also reviewed., Results and Conclusion: The growing body of literature suggests that the low rates of complications of gamma knife radiosurgery, coupled with the high success rates and patient satisfaction, allow it to be increasingly used as primary intervention for trigeminal neuralgia for appropriate patients., (2008 S. Karger AG, Basel.)

Objectives: Serum prostate specific antigen (PSA) screening has led to clinical and pathologic stage migration. We examined patients treated by radical prostatectomy between 1987 and 2005 to establish temporal trends in pathologic stage migration as assessed by the proportion of patients with nonorgan-confined disease (NOCD)., Methods: Step-sectioned prostatectomy specimens of 3364 consecutively treated patients were evaluated by year. The data were modeled by joinpoint regression, and the optimal model was selected by a Bayesian information criterion., Results: From 1987 to 2005, the population underwent pathologic stage migration toward more organ-confined tumors (P <0.0001). The proportion of patients with NOCD exhibited changes in trend at 1992 and 1995. After widespread implementation of PSA screening, stage migration accelerated between 1992 and 1995. Since 1995, stage migration has substantially slowed but continues at an annual change of -4.2% (P = 0.0027)., Conclusions: The presence of NOCD at prostatectomy has declined substantially in the PSA era. Recent slowing in this trend suggests a diminishing effect of PSA screening on pathologic stage migration.

Objectives: To examine the relationship between preoperative prostate-specific antigen (PSA) and pathologic characteristics of the prostate gland and prostate cancer at radical prostatectomy in patients with clinically localized disease in the early (1993 to 1998) and late (1999 to 2004) PSA eras., Methods: From January 1, 1993 to December 31, 2004, 2067 patients aged 40 to 80 years with clinically localized prostate cancer underwent radical prostatectomy without neoadjuvant therapy at the Cleveland Clinic. The correlation among the preoperative PSA level, prostate volume, percentage of Gleason pattern 4/5, surgical Gleason score, and cancer volume was calculated using Pearson's and Spearman's tests for the early (1993 to 1998) and late (1999 to 2004) PSA eras. Logistic regression analyses were performed to identify independent predictors of the percentage of Gleason pattern 4/5 and cancer volume during each era., Results: In both eras, the PSA level correlated positively with the percentage of Gleason pattern 4/5, surgical Gleason score, and prostate volume, with nearly identical r values. The PSA level also correlated with the cancer volume in the late PSA era (the only era for which cancer volume data were available). In the multivariate model, biopsy Gleason score, clinical T stage, and PSA level were independent predictors of percentage of Gleason pattern 4/5 in both eras and of cancer volume in the late PSA era., Conclusions: Even in the late PSA era, the preoperative PSA level has retained its predictive value for the percentage of Gleason pattern 4/5 and cancer volume. The PSA level continues to have prognostic value for men with clinically localized prostate cancer treated by radical prostatectomy.

Purpose: We evaluated biochemical relapse-free survival after surgery for localized prostate cancer, comparing rates between black and white men in the early and late prostate specific antigen eras. Our hypothesis was that the gap in biochemical relapse-free survival between these groups would lessen in the later prostate specific antigen era due to catch-up awareness/availability of screening and treatment in the black population., Materials and Methods: Data on 2,910 men treated with prostatectomy from 1987 to 2004 were evaluated. The primary end points were 1) rates of organ confined disease and 2) biochemical relapse-free survival after prostatectomy in the early (1987 to 1997) and late (1998 to 2004) prostate specific antigen eras. Rates of organ confined disease were compared using the chi-square test. Biochemical failure was analyzed using Kaplan-Meier estimates and Cox proportional hazards regression., Results: Median followup for the early and late prostate specific antigen periods was 9.8 (range 1.2 to 18.2) and 3.3 years (range 1.0 to 7.7), respectively. Based on rates of organ confined disease in the early vs late periods black and white men had significant gains in the number presenting with favorable disease at diagnosis in the late prostate specific antigen period (54% vs 76% and 49% vs 71%, respectively, each p <0.01). Despite gains of similar magnitude in favorable features at presentation biochemical relapse-free survival for black men lagged behind white men by 11% at 5 years in the early era and by 12% in the late era. Race was a significant predictor of biochemical relapse-free survival on multivariate analysis in each era., Conclusions: Despite similar increases in the rate of organ confined disease between black and white men in the late vs early prostate specific antigen eras black men continue to show higher rates of biochemical failure after surgery.

Background: The objective of the current study was to determine the histologic and molecular changes that occurred in patients with high-risk, localized prostate cancer (PCa) after neoadjuvant docetaxel chemotherapy., Methods: Patients who had locally advanced PCa (serum preoperative [initial] prostate-specific antigen [iPSA] level >or=15 ng/mL, or clinical >or=T2b disease, or biopsy Gleason score [GS] >or=8) and no evidence of metastatic disease received 6 doses of intravenous docetaxel (40 mg/m(2)) administered weekly for 6 weeks followed by radical prostatectomy (RP). The Wilcoxon signed-rank test was used to compare pretreatment and posttreatment markers., Results: Twenty-eight patients completed chemotherapy and underwent RP at the Cleveland Clinic; none achieved a pathologic complete response. Pretreatment diagnostic prostate biopsies (PBx) were reviewed in all patients, and unstained sections of formalin-fixed tissue were available from 11 patients. The median patient age was 62 years (range, 49-72 years), and the median iPSA was 6.8 ng/mL (range, 2.5-24 ng/mL). At a median follow-up of 49.5 months (range, 23-72 months), 12 patients (43%) remained clinically and biochemically free of disease with no additional therapy, and 16 patients (57%) had biochemical failure. The pretreatment GS was 6 in 2 patients (7%), 7 in 10 patients (36%), 8 in 11 patients (39%) and 9 in 5 patients (18%). Two patients (7.1%) had organ-confined disease, and 23 patients (82.1%) had extraprostatic extension. Four patients (14.3%) had positive lymph nodes, and 11 patients (39.3%) had seminal vesicle involvement. Immunohistochemical (IHC) staining for a panel of markers involved in various cellular functions (alpha-methylacyl-coenzyme A racemase [AMACR], beta-tubulin I, beta-tubulin III, cyclin D1, p27, p21, Ki-67, p53, Bcl-2, and an apoptosis detection kit [ApopTag]) was performed on a tissue microarray that contained the posttreatment (RP) tissue specimens and on the PBx specimens, if available. When the IHC staining patterns were compared between PBx and RP specimens using the Wilcoxon signed-rank test, only p53 expression (P = .017) and Bcl-2 expression (P = .014) were found to be increased significantly after neoadjuvant docetaxel treatment. However, after performing the Bonferroni adjustment, these differences were no longer significant (P > .005). Ki-67, ApopTag, beta-tubulin I, and beta-tubulin III expression levels also were increased after treatment; however, the differences were not found to be statistically significant. The expression levels of AMACR, p27, p21, and cyclin D1 were comparable in pretreatment and posttreatment specimens., Conclusions: The current results indicated that, although it will require longer follow-up studies and larger numbers of patients to ascertain the value of neoadjuvant treatment, the negative findings of the current study may explain the lack of clinical response in patients who received neoadjuvant docetaxel for PCa. Although the results were subject to interpretation limits based on the study size, the increased expression of p53 and Bcl-2 that was detected after treatment using the Wilcoxon signed-rank test suggested that the apoptotic pathway may be an important target for this drug, and further investigation is warranted., ((c) 2007 American Cancer Society.)

Objectives: No consensus exists regarding the prognostic value of tumor volume (TV) in predicting biochemical recurrence (BCR) of prostate cancer, especially late in the prostate-specific antigen (PSA) era. We assessed this relationship in a large cohort of patients treated at one institution with standardized pathologic assessment from 1998 to 2005., Methods: Data were collected for 1833 patients undergoing radical prostatectomy for clinically localized prostate cancer since 1998. Patients receiving neoadjuvant or adjuvant therapy or with node-positive disease were excluded. Along with the routine pathologic assessment, TV was prospectively assessed in all specimens. BCR was defined as two consecutive PSA levels of 0.2 ng/mL or one PSA level of greater than 0.2 ng/mL., Results: Although a larger TV correlated with lower rates of biochemical relapse-free survival in patients with a surgical Gleason score of 7 (P <0.0001) and surgical Gleason score of 8 or greater (P = 0.0459), the biochemical relapse-free survival rate at 4 years for low, medium, and extensive surgical Gleason score 6 or less tumors was 95%, 96%, and 97%, respectively (P = 0.65). In a multivariate model, including TV, initial PSA, EPE, seminal vesicle invasion, and surgical Gleason score, the TV predicted for BCR (P = 0.0176)., Conclusions: The results of this large study suggest that a large TV is an independent predictor of BCR in patients with tumors of specimen Gleason score 7 or higher. In contrast, most grade 6 tumors will be organ confined, even if of high volume, and TV will not predict for BCR in these patients.

Background: The learning curve for surgery--i.e., improvement in surgical outcomes with increasing surgeon experience--remains primarily a theoretical concept; actual curves based on surgical outcome data are rarely presented. We analyzed the surgical learning curve for prostate cancer recurrence after radical prostatectomy., Methods: The study cohort included 7765 prostate cancer patients who were treated with radical prostatectomy by one of 72 surgeons at four major US academic medical centers between 1987 and 2003. For each patient, surgeon experience was coded as the total number of radical prostatectomies performed by the surgeon before the patient's operation. Multivariable survival-time regression models were used to evaluate the association between surgeon experience and prostate cancer recurrence, defined as a serum prostate-specific antigen (PSA) of more than 0.4 ng/mL followed by a subsequent higher PSA level (i.e., biochemical recurrence), with adjustment for established clinical and tumor characteristics. All P values are two-sided., Results: The learning curve for prostate cancer recurrence after radical prostatectomy was steep and did not start to plateau until a surgeon had completed approximately 250 prior operations. The predicted probabilities of recurrence at 5 years were 17.9% (95% confidence interval [CI] = 12.1% to 25.6%) for patients treated by surgeons with 10 prior operations and 10.7% (95% CI = 7.1% to 15.9%) for patients treated by surgeons with 250 prior operations (difference = 7.2%, 95% CI = 4.6% to 10.1%; P<.001). This finding was robust to sensitivity analysis; in particular, the results were unaffected if we restricted the sample to patients treated after 1995, when stage migration related to the advent of PSA screening appeared largely complete., Conclusions: As a surgeon's experience increases, cancer control after radical prostatectomy improves, presumably because of improved surgical technique. Further research is needed to examine the specific techniques used by experienced surgeons that are associated with improved outcomes.

Objective: To investigate the detection rate and extent of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands (AG) suspicious for prostate cancer, and the cancer risk in subsequent biopsies, diagnosed by a first 24-core saturation biopsy, as although the optimum extent of biopsy is controversial there is a trend to increase the number of cores taken, and apart from detecting prostate cancer, identifying HGPIN and AG is associated with a greater risk of finding cancer in subsequent biopsies, thus warranting a closer follow-up., Patients and Methods: The study included 100 men with consecutive first-time saturation biopsies; the indications for biopsy were an abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level of >2.5 ng/mL. Each biopsy specimen was reviewed retrospectively by two pathologists to confirm the histological diagnosis. The number and percentage of cores positive for HGPIN, bilateral involvement and multifocality (HGPIN involving two or more cores) were recorded in each case. The presence of AG and cancer was also recorded. An extended (10-12 cores) repeat biopsy was available in 23 patients., Results: The median (range) age and PSA level of the patients was 63 (41-80) years and 4.9 (1.5-67.0) ng/mL, respectively. Of the 100 patients, 34% had normal findings (benign prostatic tissue, BPT), 39% had cancer, 26% had HGPIN and cancer, 22% had HGPIN alone, and 5% had AG. Repeat biopsies were available in nine of the 22 (41%) patients with HGPIN, four of five with AG, and 10 of the 34 (29%) with BPT. The median (range) interval between the first and second biopsy was 13 (4-36) months. Prostate cancer was detected at the second biopsy in a third of patients with isolated HGPIN on the first biopsy, and one of the four with AG. None of the patients with BPT had cancer on re-biopsy. The cancer detection rate was significantly greater in patients with multifocal than in those with unifocal HGPIN (80% vs none, P = 0.010). The median number of cores and percentage of tissue involved by HGPIN was 3.5 (2-5) and 1.0 (0.5-1.2)%, respectively, in patients with cancer detected in repeat biopsies, compared to 1.0 (1-3) and 0.2 (0.2-0.6)% in patients without cancer on repeat biopsy (P = 0.023 and 0.015, respectively)., Conclusion: Identifying multifocal HGPIN on first saturation biopsy is associated with an overall cancer detection rate of 80% on repeat 10-12-core biopsy. Although there were few patients, the detection of multifocal HGPIN warrants additional searches for concurrent invasive carcinoma by repeated biopsy.

Objectives: To estimate the disease-specific survival of patients with complete removal of the seminal vesicles (SVs) at radical prostatectomy and to develop a nomogram for the prediction of SV invasion (SVI)., Methods: An analysis of 6740 patients from three institutions was performed. The primary outcome was biochemical failure analyzed according to the presence or absence of SVI using the Kaplan-Meier method and Cox proportional hazards model. The variables analyzed included age, biopsy Gleason score, clinical T stage, margin status, extracapsular extension, SVI, surgical Gleason score, initial prostate-specific antigen level, and institution. Logistic regression analysis was used to determine the preoperative factors predicting for SVI and create the model for the nomogram., Results: Of the 6740 patients, 566 (8.4%) had positive SVs. The median follow-up was 33.4 months (range 1 to 239). The 5 and 10-year biochemical relapse-free survival rate was 38.0% and 25.6%, respectively, for patients with positive SVs and 85.7% and 77.2%, respectively, for patients with negative SVs (P <0.0001). In the multivariate model, all variables, except for biopsy Gleason score and T stage, were significant predictors of biochemical failure (P <0.05), and all variables, except for age, were predictors of SVI. The nomogram achieved an area under the curve of 0.80., Conclusions: These results have demonstrated that a substantial number of patients with SVI are disease free at 5 and 10 years after complete excision without adjuvant therapy. These findings suggest the therapeutic efficacy of complete SV excision and can identify those with a nomogram-predicted increased risk of SVI who might benefit from complete excision.

Objectives: To evaluate the rates of local and systemic progression (LP and SP), recurrence-free survival and overall survival for patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection (PLND) in 1987-2000., Patients and Methods: A consecutive series was analysed of 385 patients (median age 61.9 years, range 30.7-83.8) treated by limited bilateral PLND and radical cystectomy (RC) between 1987 and 2000, with negative surgical margins on final pathology. All patients were staged N0M0 before RC, and none received neoadjuvant radiotherapy or chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and bifurcation of iliac vessels to the circumflex iliac vein. LP was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Pathological characteristics, based on the 1997 Tumour-Nodes-Metastasis system, recurrence patterns, and recurrence-free and overall survival, were determined. RESULTS The median (range) overall follow-up was 45.1 (1.1-165.6) months; the number of lymph nodes (LNs) reported per patient was 12 (2-32). Of the 385 patients, 130 (33.8%) had evidence of LP and 60 (15.6%) of SP. The 5-year recurrence-free and overall survival rates were both 71% for patients with organ-confined, N0 tumours, and 23% and 26% for unconfined, N0 tumours. Positive LNs were found in 45 (12%) patients, who had a recurrence-free and overall survival rate of 9% at 5 years., Conclusion: Compared with published reports of similar cohorts of patients managed with RC and extended PLND, the present study suggests that limited PLND is associated with suboptimal staging, greater rates of LP, and lower rates of recurrence-free survival, particularly for patients with unconfined or LN-positive disease.

Purpose: To report on 32 patients who survived > or = 5 years from brain metastases treated at a single institution., Methods and Materials: The records of 1288 patients diagnosed with brain metastases between 1973 and 1999 were reviewed. Patients were treated with whole-brain radiation therapy (WBRT), surgery, and/or stereotactic radiosurgery (SRS). Thirty-two (2.5%) > or = 5-year survivors were identified. Factors contributing to long-term survival were identified., Results: Median survival was 9.3 years for > or = 5-year survivors. Seven of these patients lived > or = 10 years. Female gender was the only patient characteristic that correlated with better survival (p = 0.0369). When these patients were compared with < 5-year survivors, age < 65 years (p = 0.0044), control of the primary at diagnosis (p = 0.0052), no systemic disease (p = 0.0012), recursive partitioning analysis (RPA) Class 1 (p = 0.0002 with Class 2; p = 0.0022 with Class 3), and single brain metastasis (p = 0.0018) were associated with long-term survival in the univariate logistic regression model. In the multivariate model, RPA Class 1 compared with Class 2 (OR = 0.39, p = 0.0196), surgery (OR = 0.16, p < 0.0001), and SRS (OR = 0.41, p = 0.0188) were associated with long-term survival., Conclusions: For patients with good prognostic factors such as young age, good RPA characteristics and single metastasis, treatment with surgery or SRS offers the best chance for long-term survival.

Objectives: To report a series of patients with mucinous (colloid) adenocarcinoma (MC) at prostatectomy who were treated at a single institution from 1987 to 2005. MC is a rare form of prostate cancer reported in some cases to have a more aggressive clinical course than conventional adenocarcinoma (AC)., Methods: Radical prostatectomy specimens with mucinous features were identified from a database of 3613 consecutive patients. Each case was reviewed again by a single pathologist who confirmed the diagnosis of MC in 14 patients. MC was defined by the presence of pools of extracellular mucin in more than 25% of the tumor. Eighteen additional cases were identified in which the mucinous component occupied only a small portion of the tumor and were referred to as AC with focal mucin (AFM). The biochemical and overall survival of 26 patients with MC or AFM who had completed > or = 6 months of follow-up was analyzed using Kaplan-Meier estimates., Results: No patients with MC or AFM died of disease, and 11 (91.7%) of 12 patients with MC and 9 (64.3%) of 14 patients with AFM were clinically and biochemically free of disease. No significant difference was found in biochemical recurrence or overall survival between those with MC or AFM and a matched group of patients with AC., Conclusions: We report what we believe to be the largest published series of cases of MC (n = 14) with a median overall follow-up of 6.4 years. MC appears to behave clinically in a similar fashion to AC, with no statistically significant difference in biochemical failure or survival.

Objectives: To report biochemical relapse-free survival (bRFS) after radiotherapy (RT) for localized prostate cancer with two separate failure definitions and compare the results with those after radical prostatectomy (RP)., Methods: The study sample comprised 2516 patients with a median follow-up of 78 months. Biochemical relapse after RT was defined as either the American Society for Therapeutic Radiology Oncology definition (definition A [DefA]) or a prostate-specific antigen elevation of more than 2 ng/mL greater than the nadir prostate-specific antigen level (definition N [DefN]). Failure after RP was defined as a prostate-specific antigen level greater than 0.2 ng/mL., Results: Compared with DefA, DefN resulted in a 13% greater bRFS rate at 5 years and a 12% lower bRFS rate at 10 years. On multivariate analysis, the treatment modality (RP versus RT) was a significant predictor of bRFS using DefA in favor of RP (P <0.001), but was not with DefN (P = 0.87). Higher radiation doses were independently associated with a better outcome with either definition., Conclusions: Compared with DefA, DefN resulted in better outcomes for up to 7 years after RT, but worse outcomes thereafter. The use of DefA versus DefN resulted in opposite conclusions about the relative efficacies of RT and RP, with DefN suggesting RT is equivalent to RP and DefA that it is worse than RP. Different definitions of biochemical failure after RT can result in differences in the conclusions about treatment efficacy in men with localized prostate cancer, thereby potentially affecting clinical decisions.

Purpose: To report on the aggressiveness of sporadic versus familial prostate cancer., Patients and Methods: The study sample consisted of 4,112 stage T1-3 prostate cancer patients. The outcome of interest was biochemical relapse-free survival (bRFS). The analysis was performed for two distinct time periods, 1986 to 1992 (year < or = 1992) and 1993 to 2002 (year > or = 1993), to encompass both the early and late prostate-specific antigen (PSA) eras., Results: A positive family history (FH positive) was reported in 16%. The 10-year bRFS rates for patients with negative family history (FH negative) versus FH positive were 59% and 63%, respectively (P = .90). However, in the year < or = 1992 period, the 10-year bRFS rates for FH negative versus FH positive were 45% and 34%, respectively (P = .015). In the year > or = 1993 period, the 10-year bRFS rates for FH negative versus FH positive were 61% and 67%, respectively (P = .54). Multivariate analysis failed to reveal family history as an independent predictor of relapse (P = .42). However, in the subset of patients in each era, family history was an independent predictor of relapse only for those treated in the year < or = 1992 period (P = .038)., Conclusion: Family history was an independent predictor of biochemical failure only early in the PSA era, and men with an FH positive presented with more favorable disease later in the PSA era. This suggests that with stage migration and improved therapy, the impact of family history on prognosis has become minimal. However, underlying genetic factors affecting prostate cancer behavior in individuals with familial prostate cancer may still be important in determining individual prognosis.

Prostate-specific antigen (PSA) screening has resulted in a profound clinical stage migration. Extracapsular extension (ECE) presents a poor prognosis after radical prostatectomy (RP). In this study the trends in rate of ECE for cancers detected by PSA screening between 1987, when PSA screening became routine in the United States, and 2001, were examined. The clinical outcome of patients (total 1505; 888 clinical Tlc, 614 clinical T2, and 3 clinical T3) with prostate cancer diagnosed by PSA screening and treated with RP without neoadjuvant hormonal therapy was analyzed. The primary outcome variable was ECE rate with respect to year of treatment for a given tumor stage, preoperative PSA level, biopsy Gleason score, and surgical Gleason score. Logistic regression analysis was used to identify predictors of ECE. Biochemical relapse-free survival (bRFS) by year of treatment was analyzed by Kaplan-Meier Curve. Rate of ECE decreased from 65.8 to 25.2% during the 15-year study duration. Multivariate analysis of clinical tumor stage, age, preoperative serum PSA level, and Gleason score confirmed that year of treatment was an independent predictor of ECE. Six-year bRFS rates (by years of treatment) were 75.1% for 1987 to 1994 and 82.6% for 1995 to 2001 (P-value = 0.0022). PSA screening has resulted in a downward pathological stage migration. These observations demonstrate improved biochemical failure rates in more recently treated patients., (Copyright 2004 Elsevier Inc.)

Background and Purpose: To review the freedom from biochemical recurrence (FBR) rates after permanent prostate brachytherapy (PPB), external beam radiotherapy (RT) to a minimum 70Gy, or radical prostatectomy (RP) for clinically localized stage T1-T2 adenocarcinoma of the prostate., Patients and Methods: The study cohort consisted of 1819 consecutively treated clinical stage T1-T2 (AJCC 1997) localized prostate cancer patients between 1992 and 1998. All patients received monotherapy treatment without additional adjuvant therapy. The distribution by treatment modality was as follows: RT for 340, RP for 746, and PPB for 733 cases. The median follow-up time was 58 months for all cases (51 months for PPB cases, 56 months for RT cases, and 64 months for RP cases). Biochemical relapse was defined as to be detectable PSA levels in RP cases, and the ASTRO consensus panel definition for the RT and PPB cases., Results: The 7-year FBR rates for PPB vs EBRT vs RP were 74, 77, and 79%, respectively. Multivariate analysis identified iPSA (P < 0.001) and bGS (P < 0.001) as independent predictors of relapse. Treatment modality, age, clinical T-stage, and race were not independent predictors of failure., Conclusions: Pretreatment PSA levels, and biopsy Gleason score determined outcome in this study cohort. Biochemical failure rates in this study cohort are similar between PPB, RT, and RP as monotherapy for clinically localized prostate cancer.

Objectives: To compare differences in the actuarial biochemical relapse-free survival rates at 6 years in a contemporary series of patients who underwent radical prostatectomy with and without pelvic lymph node dissection (PLND). Biochemical failure was defined as a serum prostate-specific antigen level greater than 0.2 ng/mL confirmed at least 1 week later., Methods: The records of 806 consecutive radical prostatectomy cases performed between January 1995 and June 1999 were reviewed. A total of 336 patients with favorable tumor characteristics (prostate-specific antigen 10 ng/mL or less, biopsy Gleason score 6 or less, and clinical Stage T1 or T2) not receiving adjuvant or neoadjuvant therapy were divided into two groups according to whether PLND was performed (PLND group, n = 140) or omitted (no-PLND group, n = 196). A Cox proportional hazards model was used to analyze the effect of age, race, family history, initial prostate-specific antigen level, tumor stage, biopsy Gleason score, PLND, extracapsular extension, and seminal vesicle invasion on the likelihood of biochemical failure. Biochemical relapse-free survival for each group was estimated by Kaplan-Meier analysis. The mean follow-up time for the entire group was 60.0 months, with a similar follow-up for both cohorts (mean 61.8 and 58.2 months, respectively, P value not statistically significant). Follow-up information was obtained through an institutional review board-approved prospective patient registry., Results: The 6-year biochemical relapse-free rate for the PLND versus no-PLND group was 86% and 88%, respectively (P = 0.28). On multivariate analysis, PLND was not an independent predictor of outcome (P = 0.33)., Conclusions: Our study results demonstrated that the omission of PLND in patients with favorable tumor characteristics does not adversely affect biochemical relapse rates at 6 years after surgery. Such patients can be spared the morbidity and cost of PLND without affecting the chance for cure.

Purpose: To review the biochemical relapse-free survival (bRFS) rates after treatment with permanent seed implantation (PI), external beam radiotherapy (EBRT) <72 Gy (EBRT <72), EBRT > or =72 Gy (EBRT > or =72), combined seeds and EBRT (COMB), or radical prostatectomy (RP) for clinical Stage T1-T2 localized prostate cancer treated between 1990 and 1998., Methods and Materials: The study population comprised 2991 consecutive patients treated at the Cleveland Clinic Foundation or Memorial Sloan Kettering at Mercy Medical Center. All cases had pretreatment prostate-specific antigen (iPSA) levels and biopsy Gleason scores (bGSs). Neoadjuvant androgen deprivation for < or =6 months was given in 622 cases (21%). No adjuvant therapy was given after local therapy. RP was used for 1034 patients (35%), EBRT <72 for 484 (16%), EBRT > or =72 for 301 (10%), PI for 950 (32%), and COMB for 222 patients (7%). The RP, EBRT <72, EBRT > or =72, and 154 PI patients were treated at Cleveland Clinic Foundation. The median radiation doses in EBRT <72 and EBRT > or =72 case was 68.4 and 78.0 Gy, respectively. The median follow-up time for all cases was 56 months (range 12-145). The median follow-up time for RP, EBRT <72, EBRT > or =72, PI, and COMB was 66, 75, 49, 47, and 46 months, respectively. Biochemical relapse was defined as PSA levels >0.2 for RP cases and three consecutive rising PSA levels (American Society for Therapeutic Radiology Oncology consensus definition) for all other cases. A multivariate analysis for factors affecting the bRFS rates was performed using the following variables: clinical T stage, iPSA, bGS, androgen deprivation, year of treatment, and treatment modality. The multivariate analysis was repeated excluding the EBRT <72 cases., Results: The 5-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 81%, 51%, 81%, 83%, and 77%, respectively (p <0.001). The 7-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 76%, 48%, 81%, 75%, and 77%, respectively. Multivariate analysis, including all cases, showed iPSA (p <0.001), bGS (p <0.001), year of therapy (p <0.001), and treatment modality (p <0.001) to be independent predictors of relapse. Because EBRT <72 cases had distinctly worse outcomes, the analysis was repeated after excluding these cases to discern any differences among the other modalities. The multivariate analysis excluding the EBRT <72 cases revealed iPSA (p <0.001), bGS (p <0.001), and year of therapy (p = 0.001) to be the only independent predictors of relapse. Treatment modality (p = 0.95), clinical T stage (p = 0.09), and androgen deprivation (p = 0.56) were not independent predictors for failure., Conclusion: The biochemical failure rates were similar among PI, high-dose (> or =72 Gy) EBRT, COMB, and RP for localized prostate cancer. The outcomes were significantly worse for low-dose (<72 Gy) EBRT.