Incidence of urethral stricture after primary treatment for prostate cancer: data From CaPSURE

PURPOSE: We determined the incidence of treatment for urethral stricture, including bladder neck contracture, after primary treatment for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 6,597 men with newly diagnosed, localized prostate cancer and no history of urethral stricture disease were identified in the CaPSURE database. Treatment modalities included radical prostatectomy, external beam radiotherapy, brachytherapy, cryotherapy, androgen deprivation therapy, radical prostatectomy plus external beam radiotherapy, brachytherapy plus external beam radiotherapy and watchful waiting. The database was queried for patient reported history or International Classification of Diseases, 9th revision/Common Procedural Terminology codes consistent with stricture treatment after prostate cancer therapy. Time to obstruction was examined by the Kaplan-Meier method. Risk factors for stricture were examined in a multivariate Cox proportional hazards model. RESULTS: The incidence of stricture treatment was 344 of 6,597 cases (5.2%, range 1.1% to 8.4% by prostate cancer treatment type). Median followup was 2.7 years. In the multivariate model primary treatment type (p <0.0001), body mass index (p <0.0001) and age (p = 0.0002) were significant predictors of stricture treatment. After controlling for age and body mass index the HR for treatments compared to watchful waiting was significantly higher for radical prostatectomy (HR = 10.4, p <0.0001) and brachytherapy plus external beam radiotherapy (HR = 4.6, p = 0.0231). After radical prostatectomy most failures occurred within the first 6 months and failures were rare after 24 months, whereas after radiation failures occurred later. CONCLUSIONS: The risk of urethral stricture treatment after prostate cancer therapy is 1.1% to 8.4% depending on cancer treatment type. Risk was highest after radical prostatectomy or brachytherapy plus external beam radiotherapy and in those with advanced age or obesity. Stricture after radical prostatectomy occurred within the first 24 months, whereas onset was delayed after radiation.     

Bladder cancer risk following primary and adjuvant external beam radiation for prostate cancer

PURPOSE: Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. RESULTS: A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. CONCLUSIONS: This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.     

Monitoring intravesical therapy for superficial bladder cancer using fluorescence in situ hybridization

PURPOSE: We evaluated fluorescence in situ hybridization (FISH) for assessing the response to therapy in patients with superficial bladder cancer receiving bacillus Calmette-Guerin or other intravesical therapies. MATERIALS AND METHODS: A total of 37 patients receiving intravesical therapy for superficial bladder cancer were enrolled in this study. Urine specimens were collected for FISH analysis just prior to the first intravesical therapy in 31 cases and just prior to or within 2 months following the last intravesical therapy in 37. FISH was done using the UroVysion probe set (Abbott Laboratories, Abbott Park, Illinois) with results considered positive if 5 or more cells demonstrated polysomy. Biopsy, cystoscopy and/or cytology results were then compared to FISH results to evaluate the usefulness of the test for monitoring intravesical therapy. RESULTS: Of the patients 25 had a negative and 12 had a positive post-therapy FISH result. All 12 patients with a positive post-therapy FISH result had tumor recurrence, while tumor recurrence was observed in 13 of the 25 with a negative post-therapy FISH result (HR 4.6, 95% CI 1.9 to 11.1, p <0.001). Of the patients with tumor recurrence 7 of 12 with a positive post-therapy FISH result had muscle invasive tumor and 2 of 25 with a negative post-therapy FISH result had muscle invasive tumor (HR 9.4, 95% CI 1.9 to 45.3, p = 0.001). CONCLUSIONS: FISH appears to be useful for monitoring patients with superficial bladder cancer for the response to intravesical therapy. Patients with a positive FISH result at the end of treatment are at high risk for progression to muscle invasive bladder cancer.     

Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer

OBJECTIVE: To determine if bladder cancer diagnosed after prostatic radiation therapy (RT) differs in behaviour from bladder cancer diagnosed after prostate cancer not treated with RT, as such bladder cancer is thought to be more aggressive than de novo bladder cancer, and epidemiological studies show a higher rate of bladder cancer in patients after irradiation. PATIENTS AND METHODS: We reviewed our records to identify patients who had a diagnosis of bladder cancer with a previous diagnosis of prostate cancer. Patient age, date of diagnosis of prostate cancer, date of diagnosis of bladder cancer, symptoms, clinical stage, initial pathology, definitive therapy, definitive pathological stage, and disease status were recorded. RESULTS: In all, 100 patients were identified who had a diagnosis of bladder cancer after a diagnosis of prostate cancer between January 1992 and August 2003; 58 had had RT for prostate cancer. The mean time between a diagnosis of bladder cancer and prostate cancer was 62 months in the RT group and 34 months in the unirradiated group (P = 0.002) At diagnosis of bladder cancer, 56 (97%) of the patients who received RT had high-grade urothelial carcinoma, vs 27 (64%) of those not irradiated (P < 0.001). Thirty (52%) of the patients with RT had muscle-invasive bladder cancer, vs 17 (40%) of those not irradiated (P = 0.3). The survival rate was similar for both groups. CONCLUSIONS: Bladder cancer is diagnosed later, and is of higher grade, in patients who are irradiated for prostate cancer than in those treated with other methods. Patients with prostate cancer who are treated with RT should be monitored closely for the presence of bladder cancer.     

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.     

Ability of 2 pretreatment risk assessment methods to predict prostate cancer recurrence after radical prostatectomy: data from CaPSURE

PURPOSE: Two methods widely used to predict the risk of treatment failure after radical prostatectomy for localized prostate cancer are the 3 level D'Amico risk classification and the Kattan nomogram. Although they have been previously validated, to our knowledge they have not been compared in a community based cohort. We tested the 2 instruments in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, a national registry of patients with prostate cancer, to assess their accuracy in a community based cohort. MATERIALS AND METHODS: Men were invited to join CaPSURE from 33 American urology practices, of which 30 were community based. A total of 1,701 men with localized prostate cancer (T1-3a) were treated with radical prostatectomy between 1989 and 2000. Patients who received neoadjuvant or adjuvant therapy were excluded. Recurrence was defined as 2 or more consecutive prostate specific antigen measurements of 0.2 ng/ml or greater, or a second treatment greater than 6 months after surgery. Freedom from progression (FFP) was based on life table estimates and Kaplan-Meier curves. Risk groups were compared using a Cox proportional hazards model and ANOVA. RESULTS: Based on the D'Amico classification 671 cases (39%) were classified as low risk, 446 (26%) were intermediate risk and 584 (34%) were high risk. Five-year FFP was 78%, 63% and 60% in the low, intermediate and high risk groups (HR 1.00, 1.87 and 2.32 respectively, p <0.0001). Mean 5-year FFP predicted by the Kattan nomogram in the same risk groups was 91%, 74% and 69%, respectively. Outcomes in the low risk group were tightly grouped about the mean but there was considerable dispersion of outcomes in the intermediate (30% to 98% FFP) and high (17% to 98%) risk groups. CONCLUSIONS: Stratifying patients in CaPSURE into low, intermediate and high risk categories for disease as described by D'Amico or applying the Kattan nomogram resulted in statistically significant differences in predicted 5-year FFP. However, there was considerable overlap of outcomes between the intermediate and high risk groups. This analysis suggests that simply estimating disease recurrence by stratifying patients into low, intermediate and high risk groups may not provide sufficient information for predicting outcomes among individuals.     

Treatment of patients with high risk localized prostate cancer: results from cancer of the prostate strategic urological research endeavor (CaPSURE)

PURPOSE: Pretreatment risk assessment models facilitate more appropriate selection of treatment for prostate cancer. However, men with high risk disease remain a challenge with significant potential for primary treatment failure. We characterize patterns of treatment for high risk prostate cancer in a community based cohort. MATERIALS AND METHODS: In the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, a longitudinal disease registry of men with prostate cancer, we identified those with nonmetastatic, high risk disease based on T stage, tumor grade and serum prostate specific antigen (PSA). Differences in primary treatment, and the use of neoadjuvant and adjuvant therapy in patients at low, intermediate and high risk were assessed. In the high risk cohort predictors of the type of primary treatment, and the use of neoadjuvant and adjuvant androgen therapy were identified. RESULTS: Of the cancers 34%, 40% and 26% were low, intermediate and high risk, respectively. Differences in primary treatment type among the 3 risk groups were statistically significant (p <0.0001) with increasing external beam radiation therapy and androgen deprivation, and decreased surgery, brachytherapy and surveillance in men with high risk cancers. In this group older age, higher PSA and nonprivate insurance were associated with decreased use of radical prostatectomy. More than half of the men at high risk receiving radiation therapy also received androgen deprivation, which was significantly higher than in the low and intermediate risk groups (p <0.0001). Factors associated with androgen deprivation in high risk disease were primary therapy, PSA, Gleason sum, T stage, body mass index, insurance status and ethnicity. PSA and Gleason sum were the primary determinants of adjuvant radiation after prostatectomy. CONCLUSIONS: Men with high risk but nonmetastatic prostate cancer are more likely to receive radiation therapy as well as androgen deprivation with the latter as primary therapy or in conjunction with local treatment. These data stress the importance of pretreatment risk stratification, education regarding appropriate combinations of local and systemic therapies, and the consideration of novel clinical trials in patients at higher risk.     

Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance,Epidemiology and End Results Program data base

PURPOSE: The benefit of pelvic lymphadenectomy in patients with bladder cancer remains controversial. We analyzed the impact of lymphadenectomy on disease specific survival in a population based sample of patients with bladder cancer who underwent radical cystectomy. MATERIALS AND METHODS: Analysis included data on 1,923 patients who underwent radical cystectomy for bladder cancer between 1988 and 1996 obtained from the Surveillance, Epidemiology and End Results program cancer registry. We analyzed the impact of the number of lymph nodes examined, number of positive lymph nodes and ratio of positive-to-total number of lymph nodes resected on disease specific and overall survival independent of patient age, gender, stage, race, radiation and chemotherapy. RESULTS: Median followup in cystectomy cases was 63.5 months (range 0 to 131). Patients with 0 to 3 lymph nodes examined were at significantly higher risk of death from bladder cancer than those with greater than 3 (HR 1 to 1.2 versus 0.41 to 0.58). Patients with stages I/in situ, III and IV disease benefited from more extensive lymphadenectomy. In stage IV cases, while the total number of positive lymph nodes removed did not correlate with increased survival, the proportion of excised lymph nodes positive for metastatic bladder cancer tended to correlate with the risk of death from the disease. CONCLUSIONS: These results indicate significantly increased survival rates after cystectomy in patients with bladder cancer diagnosed with stages III or IV disease who have relatively more lymph nodes examined, suggesting that even some with higher stage disease may benefit from extended pelvic lymphadenectomy at cystectomy.     

Higher than expected association of clinical prostate and bladder cancers

PURPOSE: In this study we evaluated the risk of a second malignancy of the bladder or prostate in patients with a previous diagnosis of prostate cancer (PCa) or urothelial cancer (TCC). MATERIALS AND METHODS: We retrospectively analyzed all cases of PCa and TCC diagnosed between January 1996 and June 2003. Only PCa diagnosed due to abnormal digital rectal examination or increased prostate specific antigen were included. All patients with TCC presented with hematuria or irritative voiding symptoms and the diagnoses were confirmed with a tissue diagnosis. The incidence of lung, colon and renal cancers was also analyzed. RESULTS: A total of 816 men were diagnosed with PCa and/or TCC. Of 673 men initially diagnosed with PCa 21 had TCC. Of 149 men initially diagnosed with TCC 18 had PCa. Average age at PCa and TCC diagnosis +/- SD was 68.2 +/- 7.9 and 68.2 +/- 10.4 years, respectively. The standardized incidence ratio (SIR) of TCC in patients with PCa (SIR 4.31, 95% CI 2.411 to 7.110) and of PCa in patients with TCC (SIR 3.83, 95% CI 1.911 to 6.858) was significantly increased. There was no statistical significant difference in SIR for TCC in men with or without radiotherapy. SIR for lung, renal or colon cancer was not significantly different from what was expected. CONCLUSIONS: Patients with PCa have higher incidence of bladder cancer and those with bladder cancer have a higher incidence of PCa. This study has clinical implications in the care of these patients and it may stimulate research interest that may identify common pathways of carcinogenesis.     

Patterns of secondary cancer treatment for biochemical failure following radical prostatectomy: data from CaPSURE

PURPOSE:Biochemical failure after definitive treatment for localized prostate cancer may occur in a substantial number of patients. The pattern and type of treatment offered to such patients have been poorly documented. We determined second treatment patterns in patients with biochemical failure following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 303 patients treated with RP who had biochemical failure were identified from CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor, Tap Pharmaceutical Products, Inc., Lake Forest, Illinois), a national longitudinal registry of men with prostate cancer. Failure was defined as 2 or more prostate specific antigen (PSA) values 0.2 or greater following RP. The timing and type of secondary cancer treatment were determined. Cox proportional hazards regression analysis was conducted to determine significant predictors of time to secondary treatment, and logistic regression was used to determine predictors of the type of secondary treatment (androgen deprivation versus radiation). RESULTS: Of the 303 patients with biochemical failure 102 (33.7%) received second treatment a mean of 12 months after failure was documented. Second treatments were divided between androgen deprivation (57%) and radiation (43%). On multivariate analysis predictors of second treatment were clinical stage, biopsy Gleason score and PSA at failure. Patients with higher PSA at diagnosis and seminal vesicle invasion were more likely to receive androgen deprivation than radiation as second treatment. CONCLUSIONS: Second treatment timing and type after biochemical failure for patients initially treated with RP were documented. Clinical characteristics, such as PSA, Gleason score and clinical stage, can be used to determine which patients are at highest risk for second treatment after RP and can help guide subsequent treatment decisions.     

Adjuvant chemotherapy with paclitaxel and carboplatin in patients with advanced bladder cancer: a study by the Hellenic Cooperative Oncology Group

PURPOSE: Radical cystectomy represents the treatment of choice for muscle infiltrative bladder carcinoma. Adjuvant chemotherapy has been used to improve outcome after cystectomy. We report results in a prospective cohort of patients at high risk for relapse who were treated with the combination of paclitaxel and carboplatin as adjuvant treatment following cystectomy for muscle invasive bladder cancer. MATERIALS AND METHODS: A total of 92 patients with extravesical tumor extension (pT 3b or greater) or lymph node involvement (N+) were treated with 4 cycles of paclitaxel at 175 mg/m and carboplatin (area under the curve 5 according to the Calvert formula) every 3 weeks following radical cystectomy. Patients were followed every 6 months thereafter. RESULTS: Median followup was 36.6 months. Chemotherapy was well tolerated with 62% of patients receiving 100% of the expected chemotherapy doses without delays. Grade 3 or 4 neutropenia was reported in 19% of patients, while neutropenic fever was reported in 7%. Five-year overall, cause specific and disease-free survival was 28.9% (95% CI 14.8 to 43.0), 36.6% (95% CI 24.4 to 49.7) and 29% (95% CI 16.3 to 42.4), respectively. CONCLUSIONS: Adjuvant chemotherapy with paclitaxel and carboplatin is feasible and could be used as adjuvant treatment for high risk bladder carcinoma. Its true value should be assessed in prospective, randomized trials.     

Population based study of hormonal therapy and survival in men with metastatic prostate cancer

PURPOSE: Although the palliative benefits of hormonal therapy for metastatic prostate cancer are widely recognized, little information is available regarding the effect of hormonal therapy on cancer specific and overall survival, and the types of patients who might benefit the most or least from hormonal therapy. MATERIALS AND METHODS: Prostate cancer specific and overall survival according to hormonal therapy use was determined by the Kaplan-Meier method in 6,098 men 65 years or older diagnosed with metastatic prostate cancer in 1991 to 1999 who were identified through the population based Surveillance, Epidemiology, and End Results, and Medicare linked database. Cox proportional hazards and propensity score methods were used to adjust for potential confounders, such as disease status and patient comorbidity. RESULTS: Propensity score adjusted median overall survival was 26 months in men who received hormonal therapy compared with 13 months in those who did not (HR 0.66, 95% CI 0.17-0.70, p <0.0001). The benefit of hormonal therapy was observed across all comorbidity strata and races. Effects were most evident in patients with poorly differentiated cancer (cancer specific mortality in favor of treatment HR 0.60, 95% CI 0.53-0.69, p <0.001). Benefit was not found in patients with well differentiated cancer (cancer specific mortality in favor of no treatment HR 1.92, 95% CI 0.90-4.10, p = 0.09). CONCLUSIONS: Hormonal therapy is associated with improved prostate cancer specific and overall survival in men with poorly differentiated cancer. Improved survival does not appear evident in men with well differentiated disease.     

Diabetes and the risk of prostate cancer: the role of diabetes treatment and complications

Epidemiologic evidence suggests diabetic men have a slightly lower prostate cancer risk than non-diabetic men. We examined this association in a prospective cohort study of 35 239 men, 50-76 years old, in Washington State who completed a baseline questionnaire between 2000 and 2002. Incident prostate cancers as of 31 December 2004 were identified through the SEER registry. Diabetic men had a slightly lower risk of prostate cancer than non-diabetic men (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.64-1.07). Insulin users overall and insulin users with diabetic complications had decreased risks, compared to non-diabetic men (HR 0.49, 95% CI 0.26-0.92) and (HR 0.36, 95% CI 0.15-0.87), respectively. Oral medication use for diabetes was not associated with prostate cancer. Insulin is likely a marker of severity of diabetes. Future studies of this association should consider diabetes type, treatment, severity, complications and biomarkers.     

Radical prostatectomy for clinically localized, high risk prostate cancer: critical analysis of risk assessment methods

PURPOSE: Standardized criteria are lacking to define high risk, clinically localized prostate cancer before definitive treatment. Reliance on simple risk stratification schemes to define high risk cancers has led many physicians and patients toward therapeutic nihilism, inappropriately selecting androgen deprivation instead of definitive local therapy. Of patients undergoing radical prostatectomy we identified those at high risk based on 8 previously described definitions. We examined pathological characteristics and prostate specific antigen outcomes. MATERIALS AND METHODS: The study population included 4,708 men treated with radical prostatectomy alone between 1985 and 2004. Estimates of prostate specific antigen relapse for patients at high risk were generated with the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the HR for recurrence in high risk vs nonhigh risk cohorts. RESULTS: Depending on the definition used patients at high risk composed 3% to 38% of the study population. The proportion of patients with extracapsular extension, seminal vesicle invasion and lymph node metastasis among men with high risk cancer was 35% to 71%, 10% to 33% and 7% to 23%, respectively. Of the high risk tumors 22% to 63% proved to be confined to the prostate pathologically. While patients at high risk had a 1.8 to 4.8-fold increased hazard of prostate specific antigen relapse, their 5-year relapse-free probability after radical prostatectomy alone was 49% (95% CI 39 to 58) to 80% (95% CI 77 to 83). Of patients at high risk who had relapse 25% across all definitions experienced relapse more than 2 years after surgery and in 26% to 39% prostate specific antigen doubling time at recurrence was 10 months or greater. CONCLUSIONS: Patients diagnosed with high risk cancer by currently available definitions do not have a uniformly poor prognosis after radical prostatectomy. Many cancers classified clinically as high risk are actually confined to the prostate pathologically. The risk of extraprostatic disease and prostate specific antigen relapse varies greatly depending on the definition used.     

Androgen deprivation use with external beam radiation for prostate cancer: results from CaPSURE

PURPOSE: Recent data support the role of androgen deprivation in men undergoing external beam radiotherapy for prostate cancer. The benefits of neoadjuvant, concurrent or adjuvant treatment have been limited to men at intermediate and high risk. We examined the patterns and predictors of androgen deprivation in men undergoing external beam radiation therapy in CaPSURE. MATERIALS AND METHODS: CaPSURE is an observational, longitudinal disease registry, from which 932 men met study inclusion criteria. Androgen deprivation was classified as neoadjuvant-within 9 months of radiation or adjuvant-from the start of radiation to 6 months after completion. Time trends in androgen deprivation as well factors associated with combined therapy were elucidated using multivariate analyses. RESULTS: In this study 40%, 39% and 21% of men could be categorized into high, intermediate and low risk groups, respectively. Overall 42% and 33% of patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. Between 1997 and 2002 neoadjuvant hormone use increased significantly in all risk groups, including patients at low risk. On multivariate analyses only the year of diagnosis and clinical risk group were associated with receiving androgen deprivation with radiation. CONCLUSIONS: A significant increase in combined androgen deprivation and external radiation was observed in the last decade in men with intermediate and high risk disease. Nevertheless, more widespread acceptance is necessary since a substantial minority continue to receive radiation alone. Many patients with low risk disease that is amenable to radiation monotherapy also receive androgen deprivation. No clinical or sociodemographic features predicted the use of androgen deprivation with external radiation.     

Urothelial carcinoma after external beam radiation therapy for prostate cancer

PURPOSE: We reviewed the clinical course of patients in whom urothelial carcinoma developed following radiation therapy for prostate cancer. MATERIALS AND METHODS: A retrospective review of all patients between 1990 and 2005 with the diagnosis of bladder and prostate cancer was performed. Of 125 total patients new onset urothelial carcinoma developed in 11 after undergoing external beam radiation therapy for prostate cancer. RESULTS: Whole pelvis external beam radiation therapy with a proton boost to the prostate was the radiation modality in 7 of the 11 patients (64%), while the remaining 4 patients received standard external beam radiation only. Urothelial carcinoma was detected a mean of 3.07 years after completion of radiation therapy in the proton group, compared to a mean latency period of 5.75 years in the standard radiation group (p = 0.09). Average patient age at diagnosis was 72 years (range 64 to 84). All patients presented with gross hematuria and had cystoscopic findings of coexisting radiation cystitis. Of the 11 patients 5 (45%) presented with grade 3 carcinoma and eventually 7 (64%) required radical cystectomy. Urothelial tumors with sarcomatoid features (carcinosarcoma and spindle cell sarcomatoid) developed in 2 patients (18%). Of the 11 patients 10 (91%) were nonsmokers at the time of urothelial carcinoma diagnosis. CONCLUSIONS: Urothelial carcinoma in patients with previous radiation therapy for prostate cancer is often high grade, and the majority of patients have cancer progression requiring cystectomy. A high incidence of urothelial carcinoma with sarcomatoid features was seen in these patients.     

Predictors of secondary cancer treatment in patients receiving local therapy for prostate cancer: data from cancer of the prostate strategic urologic research endeavor

PURPOSE: Secondary cancer treatment is common after definitive local therapy for prostate cancer and it may be an indicator of the efficacy and cost of primary local treatment. We determined predictors of secondary cancer treatment in patients initially treated with radical prostatectomy or external beam radiation. MATERIALS AND METHODS: We examined 2,336 patients in Cancer of the Prostate Strategic Urologic Research Endeavor, a longitudinal registry of patients with prostate cancer, who underwent initial treatment with radical prostatectomy (1,744) or external beam radiation (592). Patients had at least 1 month of followup and all pretreatment information was available. The percent of patients receiving secondary cancer treatment, time to secondary treatment and type of secondary treatment delivered was determined. Multivariate analysis was done to determine independent predictors of secondary cancer treatment. In patients initially treated with prostatectomy a similar analysis was performed to identify predictors of receiving androgen deprivation versus radiation. RESULTS: A total of 590 patients (25%) received secondary cancer treatment, including prostatectomy in 391 (22%) and radiation in 199 (34%). Secondary cancer treatment was equally divided between radiation and androgen deprivation in 52% and 47%, respectively, of those initially treated with prostatectomy, while 92% initially treated with radiation received androgen deprivation. Predictors of any secondary treatment included patient age, biopsy Gleason score and prostate specific antigen at diagnosis. There was a trend toward increased secondary treatment more than 6 months after local therapy in patients initially treated with radiation. Increased age and lymph node metastases were independent predictors of receiving androgen deprivation after prostatectomy, while there was increased use of radiation in patients with positive surgical margins or extracapsular disease extension. CONCLUSIONS: Secondary treatment differs in patients initially treated with radical prostatectomy and radiation. Pretreatment factors can be used to counsel patients regarding the likelihood of secondary treatment, while age and prostatectomy results appear to determine the type of secondary treatment in those initially treated with prostatectomy.     

The natural history of androgen independent prostate cancer

PURPOSE: We describe the natural history of androgen independent prostate cancer (AIPC) in the modern prostate specific antigen (PSA) era. MATERIALS AND METHODS: Data from 160 patients diagnosed with AIPC between 1989 and 2002 were reviewed. No patient had received cytotoxic chemotherapy. Univariate and multivariate proportional hazards models were constructed to identify significant risk factors for cancer specific survival. Recursive partitioning analysis stratified patients into prognostic risk groupings. The types and frequencies of cancer specific complications per risk grouping were compared. RESULTS: The final prognostic risk model included nadir PSA on androgen deprivation therapy (p = 0.023), time to PSA recurrence (p = 0.006) and prostate specific antigen doubling time (p <0.01). Three highly independent risk groupings were identified. The observed median cancer specific survivals were 14.0 months (95% CI, 8.3-19.8), 38.4 months (95% CI, 26.9-49.9) and 89.1 months (95% CI, 69.0-109.2) for low, intermediate and high risk groupings, respectively (p <0.001). Patients in the low risk grouping experienced significantly fewer cancer specific complications (p = 0.003). CONCLUSIONS: This prognostic model stratified patients into 3 highly significant and independent risk groupings. A detailed PSA history alone is sufficient to risk stratify patients with AIPC.     

Contemporary trends in imaging test utilization for prostate cancer staging: data from the cancer of the prostate strategic urologic research endeavor

PURPOSE: Previous investigators have reported widespread overuse of imaging tests for staging clinically localized prostate cancer. In this study imaging test utilization rates were analyzed in a contemporary group of patients, and clinical and demographic predictors of testing were identified. MATERIALS AND METHODS: Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a longitudinal registry of men with various stages of prostate cancer. A total of 4,966 men met study inclusion criteria of available treatment and staging data. The rates of computerized tomography, magnetic resonance imaging and bone scans performed between the dates of diagnosis and primary treatment were analyzed in patients at 3 levels of clinical risk based on serum prostate specific antigen, Gleason sum and T stage. Time trends in test utilization were analyzed by linear regression. Contemporary rates were compared with those identified in a previous analysis of an earlier CaPSURE cohort. Demographic and clinical predictors of utilization were identified using generalized linear model analysis. RESULTS: Since June 1997, the overall use of staging tests has decreased 63%, 25.9% and 11.4% in patients at low, intermediate and high risk, respectively. The most precipitous decrease was noted for bone scan but the use of cross-sectional imaging also decreased in all groups. Utilization rates were lower in 2001 than in any other year studied in CaPSURE. CONCLUSIONS: The rates of testing decreased significantly in all risk groups. However, in the absence of established clinical practice guidelines many patients at low and intermediate risk continue to undergo unnecessary testing, while a growing number of those at high risk are proceeding to treatment without previous imaging.     

The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer

PURPOSE: We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates. RESULTS: The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01). CONCLUSIONS: Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.