Feasibility of brachytherapy as monotherapy for high-volume, low-risk prostate cancer.

BACKGROUND: We sought to determine whether patients with high-volume, low-risk prostate cancer are suitable candidates for ultrasound-guided brachytherapy, monotherapy alone, without supplemental external beam radiation. MATERIALS AND METHODS: The study cohort comprised 200 consecutive patients who received ultrasound.guided monotherapy from November 02, 1998 to March 26, 2010. Real.time intraoperative treatment planning was performed for all patients. 145. Gy with I125 was prescribed to the prostate with no margin. The primary endpoint was time to prostate-specific antigen. (PSA) failure using the phoenix definition. Cox multivariable regression analysis was used to determine the factors significantly associated with time to PSA failure. RESULTS: Median follow-up was 59 months (range 1.2-146.8 months). The median PSA was 5.0 ng/ml. For the overall cohort, both 5- and 8-year PSA failure-free survival was 92.3% (95% confidence interval [95% CI]: 86.5-95.7%). Low-risk patients per the NCCN criteria had 5- and 8-year PSA failure-free survival of 93.6%. On cox multivariable analysis, only baseline PSA (adjusted hazard ratio: 1.29 [95% CI: 1.02-1.65], P = 0.036) was associated with outcome. Among patients with Conclusions: Our analysis indicates that patients with a high number of cores positive for cancer can be adequately treated with modern brachytherapy as monotherapy and be spared the additional morbidity and cost of supplemental external beam radiation or androgen deprivation therapy.

Androgen deprivation therapy reversibly increases endothelium-dependent vasodilation in men with prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population. METHODS AND RESULTS: We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 ± 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05). CONCLUSIONS: In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.

Cost implications and complications of overtreatment of low-risk prostate cancer in the United States.

BACKGROUND: Evidence-based consensus guidelines recommend only observation for men with low-risk prostate cancer and life expectancy less than 10 years. This report describes the incidence, drivers, cost, and morbidity of overtreatment of low-risk prostate cancer within the United States. METHODS: The SEER-Medicare Program was used to identify 11,744 men aged 66 years or older diagnosed with low-risk prostate cancer in 2004 through 2007. Overtreatment of prostate cancer was defined as definitive treatment of a patient with a life expectancy of less than 10 years. Expected survival was estimated using NCCN methodology. Costs were the amount paid by Medicare in years after minus year before diagnosis. Toxicities were relevant Medicare diagnoses/interventions. P values are 2-sided. RESULTS: Of 3001 men with low-risk prostate cancer and a life expectancy of less than 10 years, 2011 men (67%) were overtreated. On multivariable logistic regression, overtreated men were more likely to be married (odds ratio [OR], 1.29; 95% CI, 1.05-1.59; P=.02), reside in affluent regions (P<.001), and harbor more advanced disease at diagnosis (P<.001). Two-year toxicity was greater in overtreated patients (P<.001). Relative to active surveillance/watchful waiting/observation, the median additional cost per definitive treatment was $18,827 over 5 years; the cumulative annual cost attributable to overtreatment in the United States was $58.7 million. The ability to avoid treating the 80% of men with low-grade disease who will never die of prostate cancer would save $1.32 billion per year nationally. CONCLUSIONS: Overtreatment of low-risk prostate cancer is partially driven by sociodemographic factors and occurs frequently, with marked impact on patient quality of life and health-related costs.

Lack of reduction in racial disparities in cancer-specific mortality over a 20-year period.

BACKGROUND: To the authors' knowledge, it remains unknown whether race-based differences in cancer outcomes have changed with time. In the current study, the authors assessed whether racial disparities in cancer-specific mortality have improved over the last 20 years. METHODS: The Surveillance, Epidemiology, and End Results program was used to identify 2,713,474 patients diagnosed between 1988 and 2007 with either lung, breast, prostate, or colorectal cancer (the leading 3 causes of cancer-related mortality among each sex). After exclusions, 1,001,978 patients remained eligible for analysis. The impact of race on cancer-specific mortality was assessed using the regression model of Fine and Gray; an interaction model evaluated trends over time. RESULTS: African Americans presented with a more advanced stage of disease (P < .001) and underwent definitive therapy less often (P < .001) than whites. After adjustment for demographics and year of diagnosis, African Americans were found to have higher estimates of cancer-specific mortality than whites for all cancers combined (hazards ratio, 1.28; 95% confidence interval, 1.26-1.30 [P < .001]) and within each individual cancer (each P < .05). These differences did not change significantly between 1988 through 1997 and 1998 through 2007, except among patients with breast cancer, in whom survival disparities increased. These findings remained significant after adjustment for stage of disease at presentation and receipt of definitive therapy (hazards ratio for breast cancer mortality in African Americans vs whites: 1.37 from 1988-1997 and 1.53 from 1998-2007; P for interaction, < .001). CONCLUSIONS: The survival gap for African Americans has not closed over time. Race-based differences in outcome persist independent of stage of disease and treatment, suggesting that additional strategies beyond screening and improving access to care, such as further research into tumor biologies disproportionately affecting African Americans, are needed to improve survival for African American patients with cancer.

Dosimetric quality and evolution of edema after low-dose-rate brachytherapy for small prostates: implications for the use of newer isotopes.

PURPOSE: To characterize prostate swelling and dosimetry in patients with small prostate volumes (PVs) undergoing brachytherapy. METHODS AND MATERIALS: We studied 25 patients with PV <25 cc (range, 15.1-24.8) and 65 patients with PV ≥25 cc (range, 25.0-66.2) based on three-dimensional ultrasound contours who underwent brachytherapy monotherapy with intraoperative planning. Postoperative Days 1 and 30 dosimetry was done by CT-MRI fusion. RESULTS: Small PVs had greater Day 1 swelling than large PVs (32.5% increase in volume vs. 23.7%, p = 0.04), but by Day 30, swelling was minimal and not significantly different (p = 0.44). Small PVs had greater seed and needle densities at implant (p < 0.001). Rectal and urethral doses were nearly identical by Day 30 (small PV rectum receiving 100% of the prescription dose [145 Gy] [V100] = 0.32 cc; large PV rectum V100 = 0.33 cc, p = 0.99; small PV urethra receiving 150% of the prescription dose [145 Gy] [V150] = 0.20, large PV urethra V150 = 0.20, p = 0.91). Swelling at Day 1 created some cool implants (rate dose that covers 90% of the prostate volume [D90 <140 Gy = 12.0% and 9.4% for the small and large PV groups, respectively, p = 0.71), but Day 30 planning target volume coverage was excellent (rate D90 <140 Gy = 0% for both groups). CONCLUSIONS: Although smaller prostates have greater Day 1 swelling, good Day 30 dosimetry can be achieved, making them excellent candidates for (125)I seeds (half-life [t½] = 60 days). Smaller prostates may be suboptimal for shorter t½ sources such as (131)Cs (t½ = 9.7 days), in which the majority of the dose may be delivered to an edematous gland, unless the planning is adjusted to anticipate the edema.

Marital status and survival in patients with cancer.

PURPOSE: To examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality among each of the 10 leading causes of cancer-related death in the United States. METHODS: We used the Surveillance, Epidemiology and End Results program to identify 1,260,898 patients diagnosed in 2004 through 2008 with lung, colorectal, breast, pancreatic, prostate, liver/intrahepatic bile duct, non-Hodgkin lymphoma, head/neck, ovarian, or esophageal cancer. We used multivariable logistic and Cox regression to analyze the 734,889 patients who had clinical and follow-up information available. RESULTS: Married patients were less likely to present with metastatic disease (adjusted odds ratio [OR], 0.83; 95% CI, 0.82 to 0.84; P < .001), more likely to receive definitive therapy (adjusted OR, 1.53; 95% CI, 1.51 to 1.56; P < .001), and less likely to die as a result of their cancer after adjusting for demographics, stage, and treatment (adjusted hazard ratio, 0.80; 95% CI, 0.79 to 0.81; P < .001) than unmarried patients. These associations remained significant when each individual cancer was analyzed (P < .05 for all end points for each malignancy). The benefit associated with marriage was greater in males than females for all outcome measures analyzed (P < .001 in all cases). For prostate, breast, colorectal, esophageal, and head/neck cancers, the survival benefit associated with marriage was larger than the published survival benefit of chemotherapy. CONCLUSION: Even after adjusting for known confounders, unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer. This study highlights the potentially significant impact that social support can have on cancer detection, treatment, and survival.

Cancer control and complications of salvage local therapy after failure of radiotherapy for prostate cancer: a systematic review.

The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities.

Identification of comorbidities that place men at highest risk of death from androgen deprivation therapy before brachytherapy for prostate cancer.

PURPOSE: To determine which specific comorbidities predispose men to excess mortality by androgen deprivation therapy (ADT) given before and during brachytherapy for prostate cancer. METHODS AND MATERIALS: We analyzed 5972 men with T1c-T3b prostate cancer treated with brachytherapy-based radiation with or without neoadjuvant ADT. Cox multivariable analysis with propensity scoring was used to determine if ADT was associated with increased all-cause mortality (ACM) in men divided into groups stratified by cardiac comorbidities. Tests for interaction between risk group and outcome were performed. RESULTS: ADT was associated with increased ACM in men with a history of myocardial infarction or congestive heart failure, regardless of whether they underwent revascularization (adjusted hazard ratio [AHR], 2.1 [95% confidence interval {CI}, 1.02-4.17; p=0.04]) or not (AHR, 1.8 [95% CI, 1.05-3.20; p = 0.03]), but this effect was not seen in men with less severe comorbidity. However, among men with diabetes, there was a significant interaction with risk group (p=0.01) such that ADT was associated with excess mortality in men with low-risk disease (AHR = 2.21 [1.04-4.68]; p=0.04) but not in men with intermediate or high-risk disease (AHR, 0.64 [0.33-1.22]; p=0.17). CONCLUSIONS: ADT was associated with excess ACM in all patients with a history of congestive heart failure or myocardial infarction, regardless of whether they were revascularized, and in diabetics with low-risk disease. ADT for gland downsizing before brachytherapy should be avoided in these men.

Reduced penile size and treatment regret in men with recurrent prostate cancer after surgery, radiotherapy plus androgen deprivation, or radiotherapy alone.

OBJECTIVE: To report the relative incidence of the perceived reduction in penile size across prostate cancer treatment modalities and to describe its effect on quality of life and treatment regret. MATERIALS AND METHODS: The incidence of patient complaints about reduced penile size was calculated for 948 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical failure (per registry definition) and were assessed a median of 5.53 years after prostatectomy or radiotherapy (RT) consisting of either external beam RT or brachytherapy, with or without androgen deprivation therapy (ADT). Multivariate logistic regression analysis was used to determine the factors associated with treatment regret and interference with emotional relationships. RESULTS: Of 948 men, 25 (2.63%) complained of a reduced penile size. The incidence of reduced penile size stratified by treatment was 3.73% for surgery (19 of 510), 2.67% for RT plus ADT (6 of 225), and 0% for RT without ADT (0 of 213). The surgery (P=.004) and RT plus ADT (P=.016) groups had significantly more shortened penis complaints than the RT alone group. The rate of a shortened penis after surgery and after RT plus ADT was similar (P=.47). On multivariate analysis adjusting for age, treatment type, and baseline comorbidity, a perceived reduction in penile size was associated with interference with close emotional relationships (odds ratio 2.36, 95% confidence interval 1.02-8.26; P=.04) and increased treatment regret (odds ratio 3.37, 95% confidence interval 1.37-8.26; P=.0079). CONCLUSION: Complaints about a reduced penile size were more common with RT plus ADT or surgery than RT alone and were associated with greater interference with close emotional relationships and increased treatment regret. Physicians should discuss the possibility of this rarely mentioned side effect with their patients to help them make more informed treatment choices.