Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy.

PURPOSE: Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach. MATERIALS AND METHODS: Of 5,382 men in the database who underwent primary radical prostatectomy (RP), 4,967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1,352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1,352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome. RESULTS: Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05). CONCLUSIONS: The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.

Scrotal lymphangioma in an adult.

We present a case of scrotal lymphangioma in a 25-year-old man. The patient presented with scrotal swelling and an ultrasound scan demonstrating a complex extratesticular cystic mass around the left spermatic cord. He underwent excision of the mass, followed by orchiectomy for recurrence. This case was interesting for several reasons. First, scrotal lymphangioma, although very rare, is usually seen in infants and children. Second, for a symptomatic extratesticular cystic mass, surgery might be warranted. Finally, although primary excision is the treatment of choice in the younger individual, the same might not be true for the rare adult with this disease.

Watchful waiting and factors predictive of secondary treatment of localized prostate cancer.

PURPOSE: Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. MATERIALS AND METHODS: Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. RESULTS: Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). CONCLUSIONS: Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.

Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy.

PURPOSE: Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach. MATERIALS AND METHODS: Of 5382 men in the database who underwent primary radical prostatectomy (RP), 4967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome. RESULTS: Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05). CONCLUSIONS: The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.

Pathologic variables and recurrence rates as related to obesity and race in men with prostate cancer undergoing radical prostatectomy.

PURPOSE: To determine if obesity is associated with higher prostate specific antigen recurrence rates after radical prostatectomy (RP), and to explore racial differences in body mass index (BMI) as a potential explanation for the disparity in outcome between black and white men. PATIENTS AND METHODS: A retrospective, multi-institutional pooled analysis of 3,162 men undergoing RP was conducted at nine US military medical centers between 1987 and 2002. Patients were initially categorized as obese (BMI > or = 30 kg/m(2)), overweight (BMI 25 to 30 kg/m(2)), or normal (BMI < or = 25 kg/m(2)). For analysis, normal and overweight groups were combined (BMI < 30 kg/m(2)) and compared with the obese group (BMI > or = 30 kg/m(2)) with regard to biochemical recurrence (prostate-specific antigen > or = 0.2 ng/mL) after RP. RESULTS: Of 3,162 patients, 600 (19.0%) were obese and 2,562 (81%) were not obese. BMI was an independent predictor of higher Gleason grade cancer (P <.001) and was associated with a higher risk of biochemical recurrence (P =.027). Blacks had higher BMI (P <.001) and higher recurrence rates (P =.003) than whites. Both BMI (P =.028) and black race (P =.002) predicted higher prostate specific antigen recurrence rates. In multivariate analysis of race, BMI, and pathologic factors, black race (P =.021) remained a significant independent predictor of recurrence. CONCLUSION: Obesity is associated with higher grade cancer and higher recurrence rates after RP. Black men have higher recurrence rates and greater BMI than white men. These findings support the hypothesis that obesity is associated with progression of latent to clinically significant prostate cancer (PC) and suggest that BMI may account, in part, for the racial variability in PC risk.

Factors associated with blood loss during radical prostatectomy for localized prostate cancer in the prostate-specific antigen (PSA)-era: an overview of the Department of Defense (DOD) Center for Prostate Disease Research (CPDR) national database.

Radical Prostatectomy (RP) has been traditionally associated with significant operative blood loss and high risk of transfusion. However, over the last few years, centers of excellence have reported less bleeding and transfusion. To verify and document changes in the epidemiology of bleeding and transfusion of men electing RP, we undertook an analysis of such cases in the Department of Defense (DoD) Center for Prostate Disease Research (CPDR) Multicenter Research Database. Using the Department of Defense Center for Prostate Disease Research (CPDR) Multicenter National Research Database, a query of all RPs performed between January 1, 1985 and December 31, 2000 was conducted revealing 2918 cases with blood-loss data available for analysis from nine hospital sites. These cases were analyzed over time (calendar year) and changes in the characteristics of the patients, disease severity, and surgical results were compared with estimated blood loss (EBL) and transfusion data. Among the 2918 evaluable men, 2399 (82%) underwent a retropubic RP, 97% had clinical T1-2 disease, and 77% had a PSA level > or =10.0 ng/mL. Overall median operation time was 3.8 h, and EBL was 1000 cc. Examining trends over time, there was a dramatic decline in median operative time, EBL, and transfusion rate. In multiple linear regression analysis, operative time, operative approach, surgery year, lymphadenectomy status, and neoadjuvant hormonal therapy were significant predictor of EBL. Blood loss difference between retropubic and perineal RP became insignificant in the latter years. Radical prostatectomy is being performed more commonly on men with earlier stage disease in the PSA-Era. The operation is now performed more rapidly with less blood loss and fewer transfusion requirements. In a broad practice experience represented here, autologous blood donation would appear to be unnecessary for the majority of men and the blood loss advantage traditionally associated with perineal RP is no longer evident.

Temporarily deferred therapy (watchful waiting) for men younger than 70 years and with low-risk localized prostate cancer in the prostate-specific antigen era.

PURPOSE: Watchful waiting (WW) is an acceptable strategy for managing prostate cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in a stage migration, with diagnoses made in younger men. An analysis of the Department of Defense Center for Prostate Disease Research Database was undertaken to document younger men with low- or intermediate-grade PC who initially chose WW. PATIENTS AND METHODS: We identified men choosing WW who were diagnosed between January 1991 and January 2002, were 70 years or younger, had a Gleason score < or = 6 with no Gleason pattern 4, had no more than three positive cores on biopsy, and whose clinical stage was < or = T2 and PSA level was < or = 20. We analyzed their likelihood of remaining on WW, the factors associated with secondary treatment, and the influence of comorbidities. RESULTS: Three hundred thirteen men were identified. Median follow-up time was 3.8 years. Median age was 65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215 proceeded to treatment. A total of 57.3% and 73.2% chose treatment within the first 2 and 4 years, respectively. Median PSA doubling time (DT) was 2.5 years for those who underwent therapy; those remaining on WW had a median DT of 25.8 years. The type of secondary treatment was associated with the number of patient's comorbidities (P =.012). CONCLUSION: Younger patients who choose WW seemed more likely to receive secondary treatment than older patients. PSA DTs often predict the use of secondary treatment. The number of comorbidities a patient has influences the type of secondary therapy chosen. The WW strategy may better be termed temporarily deferred therapy.

Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy.

PURPOSE: In the last decade numerous groups have shown that low levels of pretreatment serum total testosterone consistently predict more aggressive disease, worse prognosis and worse treatment response in patients with metastatic prostate cancer. Prior studies have not demonstrated this same correlation in patients with known localized disease. We rigorously tested pretreatment total testosterone levels as a potential staging and prognostic marker in a large cohort of 879 patients with localized cancer treated with radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 879 patients treated with radical prostatectomy between January 1, 1986 and June 30, 2002 from 9 hospital sites. Nonparametric tests were used to compare the relationship of pretreatment testosterone to other variables. Multivariate logistic regression analysis was used to assess clinical predictors of extraprostatic disease. Kaplan-Meier survival methods and Cox regression analysis were used to assess predictors of biochemical recurrence. RESULTS: Patients with non-organ confined prostate cancer (pT3-T4) showed significantly lower pretreatment total testosterone levels than those with organ confined cancer (pT1-T2) (nonparametric p = 0.041). In multivariate analysis pretreatment total testosterone emerged as a significant independent predictor of extraprostatic disease (p = 0.046). Total testosterone was not a significant predictor of biochemical (prostate specific antigen) recurrence (p = 0.467). CONCLUSIONS: Pretreatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer. As testosterone decreases patients have an increased likelihood of non-organ confined disease. Low testosterone was not predictive of biochemical recurrence, although trends observed dictate study in larger cohorts with mature followup.

Using the percentage of biopsy cores positive for cancer, pretreatment PSA, and highest biopsy Gleason sum to predict pathologic stage after radical prostatectomy: the Center for Prostate Disease Research nomograms.

OBJECTIVES: To develop probability nomograms to predict pathologic outcome at the time of radical prostatectomy (RP) on the basis of established prognostic factors and prostate biopsy quantitative histology. METHODS: Using information from the database of the Center for Prostate Disease Research (CPDR), univariate and multivariate analyses were performed on 1510 men who had undergone transrectal ultrasound and biopsy for diagnosis and had radical prostatectomy as primary therapy, with variables of age, race, clinical stage, pretreatment prostate-specific antigen (PSA), biopsy Gleason sum, and percentage of biopsy cores positive for cancer (total number of cores positive for cancer divided by the total number of cores obtained). The percentages of biopsy cores positive were grouped as less than 30%, 30% to 59%, and greater than or equal to 60%. The three most significant variables were used to develop probability nomograms for pathologic stage. RESULTS: PSA, biopsy Gleason sum, and percentage of cores positive were the three most significant independent predictors of pathologic stage. The assigned percentage of biopsy core-positive subgroups along with pretreatment PSA and highest Gleason sum were used to develop probability nomograms for pathologic stage. CONCLUSIONS: Pretreatment PSA, highest biopsy Gleason sum, and the percentage of cores positive for cancer are the most significant predictors for pathologic stage after radical prostatectomy. On the basis of these findings, CPDR probability nomograms were developed to predict pathologic outcome at the time of RP.

Effect of age on biochemical disease-free outcome in patients with T1-T3 prostate cancer treated with definitive radiotherapy in an equal-access health care system: a radiation oncology report of the Department of Defense Center for Prostate Disease Research.

PURPOSE: It has traditionally been a common perception that young age is a negative prognostic factor in prostate cancer (CaP). Furthermore, many urologists believe that younger patients are better suited to surgery rather than radiotherapy (RT) because of this perception. However, the data on the effect of age on outcome in patients with CaP are unclear. The records of the Department of Defense Center for Prostate Disease Research were queried for the biochemical disease-free results of patients after definitive RT and analyzed by age. MATERIALS AND METHODS: The records of 1018 patients with T1-T3 CaP treated with definitive RT between 1988 and 2000 were reviewed. The records of patients receiving adjuvant hormonal therapy or adjuvant or salvage RT postoperatively were excluded. Biochemical failure was calculated by the American Society for Therapeutic Radiology and Oncology criteria. The median potential follow-up was 85.3 months as of December 31, 2001. RESULTS: Age did not affect biochemical disease-free survival significantly when considered as <60 vs. >/=60 years (p = 0.646), by decade (p = 0.329), or as a continuous variable (correlation coefficient r = 0.017, regression slope = 0.007, with p = 0.588 and R(2) < 0.001). Using multiple regression analysis, age was still not significant (p = 0.408). Other variables analyzed were pretreatment prostate-specific antigen level (p < 0.001), Gleason sum (p = 0.023), stage (p = 0.828), and RT dose (p = 0.033). CONCLUSIONS: Age and biochemical disease-free survival after RT for CaP are not related. Age may not be a valid factor in choosing between primary treatment options for CaP.

Effect of race on biochemical disease-free outcome in patients with prostate cancer treated with definitive radiation therapy in an equal-access health care system: radiation oncology report of the Department of Defense Center for Prostate Disease Research.

PURPOSE: To report on the first collaboration of the Department of Defense Center for Prostate Disease Research concerned with the relationship between African American race and biochemical disease-free outcomes after definitive radiation therapy. MATERIALS AND METHODS: Information from the medical records of 1,806 patients (1,349 white, 343 African American, 42 of "other" races, and 72 of "unknown" races) treated with definitive radiation therapy between 1973 and 2000 was reviewed. Patients receiving adjuvant hormonal therapy or postoperative adjuvant or salvage radiation therapy were excluded. Biochemical failure was calculated in over 96% of cases by using ASTRO criteria; patients with fewer than three follow-up visits were considered to have biochemical failure with a prostate-specific antigen (PSA) value more than 10-fold the previous value or with any value greater than 50.0 ng/mL. Median radiation therapy doses were similar. The median follow-up was 58.4 months. Kaplan-Meier tests, Cox proportional hazards regression analysis, and log-rank tests were used for data analysis. RESULTS: There was no statistically significant difference in biochemical disease-free survival according to race when patients were stratified according to T stage. African American race conferred a negative prognosis for patients with lesions of Gleason biopsy score 7 (P =.004) but not for patients with lesions of Gleason score 2-4 (P =.14), 5-6 (P =.79), or 8-10 (P =.86). Similarly, African American race conferred a negative prognosis in patients with PSA values of 20.1-50.0 ng/mL (P =.01) at presentation but not in patients with PSA values less than or equal to 4.0 ng/mL (P =.84), 4.1-10.0 ng/mL (P =.71), 10.1-20.0 ng/mL (P =.75), or above 50.0 ng/mL (P =.15) at presentation. At multivariate analysis, race was not a statistically significant predictor of outcome. CONCLUSION: In the equal-access health care system of the Department of Defense, African American race is not associated with a consistently negative prognosis in patients treated with definitive radiation therapy for prostate cancer. Race appears to confer a negative prognosis only in patients with advanced disease at presentation.

Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of Defense Center for Prostate Disease Research national database.

BACKGROUND: Because of public awareness and screening, the incidence of clinically localized prostate cancer has increased dramatically in the last 15 years. The Department of Defense Center for Prostate Disease Research (CPDR) was established by the US Congress in 1991 to study prostate cancer in the US military health care system. A key component of CPDR is a multicenter prospective and retrospective prostate research database that collects comprehensive standardized data on all consenting patients. To verify and document changes in the epidemiology of men electing radical prostatectomy (RP) as primary treatment for their localized prostate cancer, we undertook an analysis of such cases when the PSA screening test became widely available and used. METHODS: The CPDR database consists of standardized data collection forms for each episode of care completed prospectively, and in some cases, retrospectively, on men with prostate cancer and those undergoing a prostate biopsy for presumed cancer at participating medical centers. In July 2001, a query of all RPs performed between January 1, 1991, and December 31, 2000, was conducted, revealing 3681 cases for analysis from 9 hospital sites. These cases were analyzed over time (calendar year), and changes in the characteristics of the patients, disease severity, and surgical results were compared. RESULTS: There was a significant shift to younger men undergoing RP with the median age declining to 62.3 years old by 2000, and more than 40% of the men were less than 60 years old. There was an increase in African-Americans undergoing RP and a large increase in clinical stage T1 disease candidates of both races representing 56.5% of men by 2000. There was a large increase in patients having pretreatment PSA levels between 4 and 10 ng/mL (59.2% by 2000). Retropubic approach was predominant (over 80%) and was associated with a much lower blood loss by 2000 (approximately 800 mL). There was an increase in use of nerve-sparing procedures, and operative time declined significantly to a median of 3.5 hours by 2000. Finally, there was a marked surgical stage migration with a higher proportion of men with organ-confined disease and negative surgical margins; by 2000, 63.4% had pT2 disease. The early outcomes improved with a 1-year disease-free survival in excess of 93%. CONCLUSIONS: RP is being performed more commonly on younger men with earlier stage disease in the PSA era. The operation is now performed more rapidly with less blood loss, and the surgical pathology outcome end points and early disease-free survival are improved. These results portend well for improved long-term outcomes of surgical therapy.