Mortality in men with localized prostate cancer treated with brachytherapy with or without neoadjuvant hormone therapy

BACKGROUND:

Discrepancies exist regarding the impact of neoadjuvant hormone therapy (NHT) on the risk of all‐cause mortality (ACM) in men who receive brachytherapy for localized prostate cancer. Therefore, the objective of the current study was to examine the effect of NHT on the risk of ACM in men with prostate cancer who receive with brachytherapy.

METHODS:

The study cohort included 2474 men with localized prostate cancer who either received NHT (N = 1083) or did not receive NHT (N = 1391) and brachytherapy without supplemental external beam radiation between 1991 and 2005 at centers within the 21st Century Oncology Consortium. All men had at least 2 years of follow‐up. Low‐risk, intermediate‐risk, and high‐risk disease was present in 65%, 23%, and 12% of men, respectively. A Cox regression multivariate analysis was used to evaluate the risk of ACM in men who received NHT compared with all others adjusting for age, prostate‐specific antigen level, Gleason score, and tumor classification.

RESULTS:

After a median follow‐up of 4.8 years (interquartile range, 3.3‐7.5 years) and adjusting for known prostate cancer prognostic factors and age, treatment with NHT was associated significantly with an increased risk of ACM (adjusted hazard ratio, 1.24; 95% confidence interval, 1.01‐1.53; P = .04) in men aged ≥73 years. In men who were younger than the median age of 73 years, hormone therapy use was not significant (P = .34).

CONCLUSIONS:

Compared with men who were younger than the median age of 73 years, men aged ≥73 years with localized prostate cancer who received brachytherapy and NHT had an increased risk of ACM compared with men who did not receive NHT. Cancer 2010. © 2010 American Cancer Society.     

Prostate cancer‐specific mortality and the extent of therapy in healthy elderly men with high‐risk prostate cancer

BACKGROUND:

The risk of prostate cancer‐specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external‐beam radiation to the prostate and seminal vesicles, and androgen‐suppression therapy (CMT) in this population.

METHODS:

The study cohort comprised 764 men aged ≥65 years with high‐risk prostate cancer (T3 or T4N0M0, prostate‐specific antigen >20 ng/mL, and/or Gleason score 8‐10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM.

RESULTS:

The median patient age was 73 years (interquartile range, 70‐77 years). After a median follow‐up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12‐0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017).

CONCLUSIONS:

Elderly men who had high‐risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high‐risk prostate cancer. Cancer 2010. © 2010 American Cancer Society.     

Dose‐escalated radiation therapy for intermediate‐risk prostate cancer

BACKGROUND:

Randomized trials supported the use of androgen deprivation therapy (ADT) with radiation therapy (RT) for intermediate‐risk prostate cancer. However, the value of concurrent ADT was less certain with dose‐escalated RT. Better methods of stratifying patients in this risk group may help select patients who are most likely to benefit.

METHODS:

A total of 238 men with intermediate‐risk (prostate specific antigen [PSA] 10‐20, Gleason 7, or stage T2b‐c) adenocarcinoma of the prostate were treated with external beam RT between 1989 and 2006. Patients had Gleason≤6 (39%) or 7 (61%) tumors; median PSA was 10.5 ng/mL. A median of 37.5% of biopsy cores were positive from a median of 9 biopsy cores sampled. The median RT dose was 74 Gy to the prostate. A total of 112 patients (47%) received neoadjuvant and concurrent ADT (median, 4 months). Median follow‐up period was 49 months.

RESULTS:

The freedom from biochemical failure (FFBF, nadir + 2 definition) was 93% at 3 years, 86% at 4 years, and 80% at 5 years. On univariate analysis, the only factor associated with FFBF was percentage of positive cores (PPC, P = .0340). The prognostic value of PPC≥50 was not evident in patients receiving ADT (FFBF at 4 years 90% vs 91%, P = .3015). For patients not receiving ADT, the impact of PPC≥50 (FFBF at 4 years 76% vs 93%, P = .0844) was more pronounced. On multivariate analysis, PPC (P = .0388) was significantly associated with FFBF, whereas Gleason sum, ADT, RT dose, PSA, and T‐stage were not.

CONCLUSIONS:

After dose‐escalated external beam RT, intermediate‐risk prostate cancer patients with PPC≥50 had the highest risk for biochemical failure and may be most likely to derive a benefit from ADT. Cancer 2009. © 2009 American Cancer Society.     

A randomized trial of internet-based versus traditional sexual counseling for couples after localized prostate cancer treatment

BACKGROUND:

After treatment for prostate cancer, multidisciplinary sexual rehabilitation involving couples appears more promising than traditional urologic treatment for erectile dysfunction (ED). The authors of this report conducted a randomized trial comparing traditional or internet‐based sexual counseling with waitlist (WL) control.

METHODS:

Couples were randomized adaptively to a 3‐month WL, a 3‐session face‐to‐face format (FF), or an internet‐based format (WEB1). A second internet‐based group (WEB2) was added to examine the relation between web site use and outcomes. At baseline, post‐WL, post‐treatment, and 6‐month, and 12‐month follow‐up assessments, participants completed the International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI), the Brief Symptom Inventory‐18 to measure emotional distress, and the abbreviated Dyadic Adjustment Scale.

RESULTS:

Outcomes did not change during the WL period. Of 115 couples that were randomized to FF or WEB1 and 71 couples in the WEB2 group, 34% dropped out. Neither drop‐outs nor improvements in outcomes differed significantly between the 3 treatment groups. In a linear mixed‐model analysis that included all participants, mean ± standard deviation IIEF scores improved significantly across time (baseline, 29.7 ± 17.9; 12 months, 36.2 ± 22.4; P < .001). FSFI scores also improved significantly (baseline, 15.4 ± 8.5; 12 months, 18.2 ± 10.7; P = .034). Better IIEF scores were associated with finding an effective medical treatment for ED and normal female sexual function at baseline. In the WEB2 group, IIEF scores improved significantly more in men who completed >75% of the intervention.

CONCLUSIONS:

An internet‐based sexual counseling program for couples was as effective as a brief, traditional sex therapy format in producing enduring improvements in sexual outcomes after prostate cancer. Cancer 2011;. © 2011 American Cancer Society.     

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

BACKGROUND.

Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.

METHODS.

The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).

RESULTS.

In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.

CONCLUSIONS.

Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.     

Comorbidity,body mass index,and age and the risk of nonprostate‐cancer‐specific mortality after a postradiation prostate‐specific antigen recurrence

BACKGROUND:

Some men with a postradiation therapy (RT) prostate‐specific antigen (PSA) recurrence will die of noncancer causes before developing metastases. Therefore, our ability to determine who would benefit from salvage hormonotherapy (HT) would be enhanced if an individual's risk of nonprostate‐cancer‐specific mortality were known.

METHODS:

Among 206 men with unfavorable‐risk localized prostate cancer initially randomized to RT+/?HT, 87 men who experienced PSA recurrence were studied. Fine and Gray's competing risks regression was used to assess whether body mass index (BMI) and the Adult Comorbidity Evaluation‐27 comorbidity level at randomization were associated with the risk of nonprostate‐cancer‐specific mortality after PSA recurrence, adjusting for age at recurrence.

RESULTS:

After a median postrecurrence follow‐up of 4.4 years, moderate/severe comorbidity (adjusted hazard ratio [HR] = 3.15; P = .02), BMI ≥ median (27.4 kg/m²; adjusted HR=2.98; p=.04), and increasing age at recurrence (adjusted HR = 1.17; P = .03) were significantly associated with an increased risk of nonprostate‐cancer‐specific mortality. Five‐year cumulative incidence estimates of nonprostate‐cancer‐specific mortality were as follows: 0% (95% confidence interval [CI] [0,0]) for low‐risk patients (mild/no comorbidity and age<median [76.2 years] and BMI<median), 18.8% (5.8‐31.8) for intermediate‐risk patients (mild/no comorbidity and either age≥median or BMI≥median); and 37.9% (95% CI, 6.8‐68.9) for high‐risk patients (moderate/severe comorbidity; P = .03 overall).

CONCLUSIONS:

After a post‐RT PSA recurrence, men with moderate/severe comorbidity and those who are obese or older face a substantial risk of nonprostate‐cancer‐specific mortality, and they could be considered for surveillance protocols with a plan to initiate salvage HT if the PSA rises rapidly (eg, PSA doubling time <6 months) or the patient develops clinically or radiographically evident disease. Cancer 2010. © 2009 American Cancer Society.     

Salvage radiation in men after prostate-specific antigen failure and the risk of death

BACKGROUND:

A survival benefit has been observed with salvage radiation therapy (RT) for prostate‐specific antigen (PSA) failure after radical prostatectomy (RP) in men with rapid rises in PSA doubling time (DT, <6 months). Whether such a benefit exits in men with a protracted PSA rise in DT (≥6 months) is unclear and was examined in the current study.

METHODS:

Of 4036 men who underwent RP at Duke University between 1988 and 2008, 519 experienced a PSA failure, had complete data, and were the subjects of this study. Univariate and multivariate Cox regression analyses were performed to evaluate whether salvage RT in men with either a rapid (<6 months) or a protracted (≥6 months) PSA DT was associated with the risk of all‐cause mortality adjusting for age at the time of PSA failure, known prostate cancer prognostic factors, and cardiac comorbidity.

RESULTS:

After a median follow‐up of 11.3 years after PSA failure, 195 men died. Salvage RT was associated with a significant reduction in all‐cause mortality for men with either a PSA DT of <6 months (adjusted hazard ratio [AHR], 0.53; P = .02) or a PSA DT of ≥6 months (AHR, 0.52; P = .003). In a subset of patients with comorbidity data at the time of PSA failure, salvage RT remained associated with a significant reduction in all‐cause mortality for both men with a PSA DT of <6 months (AHR, 0.35; P = .042) or a PSA DT of ≥6 months (AHR, 0.60; P = .04).

CONCLUSIONS:

Salvage RT for PSA DTs less than or in excess of 6 months is associated with a decreased risk in all‐cause mortality. Cancer 2011. © 2011 American Cancer Society.     

Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer

BACKGROUND:

The natural history of castration‐resistant nonmetastatic prostate cancer is poorly defined.

METHODS:

The authors used data from 331 subjects in the placebo group of a randomized controlled trial to evaluate the relations of disease and host characteristics with time to first bone metastases in men with prostate cancer, rising prostate‐specific antigen (PSA) despite androgen deprivation therapy, and no radiographic evidence of metastases. Relations between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N‐telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin.

RESULTS:

At 2 years, 46% of subjects had developed bone metastases, and 20% had died. Median bone metastasis‐free survival was 25 months. In multivariate analyses, baseline PSA ≥13.1 ng/mL was associated with shorter overall survival (relative risk [RR], 2.34; 95% confidence interval [CI], 1.71–3.21; P < .0001), time to first bone metastasis (RR, 1.98; 95% CI, 1.43‐2.74; P < .0001), and bone metastasis‐free survival (RR, 1.98; 95% CI, 1.45–2.70; P < .0001). PSA velocity was significantly associated with overall and bone metastasis‐free survival. Other covariates were not consistently associated with clinical outcomes.

CONCLUSIONS:

In men with progressive castration‐resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis‐free survival, and overall survival. Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes. Cancer 2011. © 2010 American Cancer Society.     

Hypofractionated stereotactic body radiotherapy in low-risk prostate adenocarcinoma: preliminary results of a multi-institutional phase 1 feasibility trial

BACKGROUND:

Recent reports using extreme hypofractionated regimens in the treatment of low‐risk prostate adenocarcinoma have been encouraging. Here, the authors report on their own multi‐institutional experience with extreme hypofractionated stereotactic radiotherapy for early stage disease.

METHODS:

In total, at 4 centers, 45 patients with National Comprehensive Cancer Network‐defined, low‐risk prostate adenocarcinoma were enrolled in a phase 1, multi‐institutional trial of hypofractionated radiosurgery with a proprietary radiosurgical device (CyberKnife). Thirty‐four patients received 7.5 grays (Gy) delivered in 5 fractions, 9 patients received 7.25 Gy delivered in 5 fractions, and 2 patients received other regimens. The variables evaluated were biochemical progression‐free survival (bPFS), prostate‐specific antigen (PSA) bounce, and toxicities. Health‐related quality of life was evaluated using the Sexual Health Inventory for Men (SHIM), American Urological Association (AUA), and Expanded Prostate Cancer Index Composite (EPIC) questionnaires.

RESULTS:

The median follow‐up for surviving patients was 44.5 months (range, 0‐62 months). The bPFS rate at 3 years was 97.7%. The median PSA declined from 4.9 ng/mL at diagnosis to 0.2 ng/mL at last follow‐up, and the median percentage PSA decline at 12 months was 80%. Nine patients experienced at least 1 PSA bounce ≥0.4 ng/mL, and 4 patients experienced 2 PSA bounces. The median time to first PSA bounce was 11.6 months (range, 7.2‐18.2 months), and the mean percentage PSA bounce was 1.07 ng/mL. There was 1 episode of late grade 3 urinary obstruction, and there were 2 episodes of late grade 3 proctitis. There was a significant late decline in SHIM and EPIC sexual scores and a small, late decline in the EPIC Bowel domain score.

CONCLUSIONS:

In a select population, extreme hypofractionation with stereotactic radiosurgery was safe and effective for the treatment of low‐risk prostate adenocarcinoma. Cancer 2012. © 2011 American Cancer Society.     

Age‐specific physical activity and prostate cancer risk among white men and black men

BACKGROUND:

The relation of physical activity across the lifespan to risk of prostate cancer has not been thoroughly investigated, particularly among black men. The authors investigated physical activity, including activity during different age periods and of various intensities, in relation to prostate cancer incidence among white men and black men.

METHODS:

In total, 160,006 white men and 3671 black men ages 51 years to 72 years who were enrolled in the National Institutes of Health‐AARP Diet and Health Study reported their time spent per week engaging in physical activity during ages 15 to 18 years, 19 years to 29 years, 35 years to 39 years, and during the past 10 years. Cox regression models were used to examine physical activity, categorized by intensity (moderate or vigorous, light, and total), in relation to prostate cancer risk.

RESULTS:

During 7 years of follow‐up, 9624 white men and 371 black men developed prostate cancer. Among white men, physical activity had no association with prostate cancer regardless of age period or activity intensity. Among black men, engaging in ≥4 hours of moderate/vigorous intensity physical activity versus infrequent activity during ages 19 years to 29 years was related to a 35% lower risk of prostate cancer (relative risk, 0.65; 95% confidence interval [95% CI], 0.43‐0.99 [P_trend = .01]). Frequent moderate/vigorous physical activity at ages 35 years to 39 years also potentially was related to reduced prostate cancer risk (relative risk, 0.59; 95% CI, 0.36‐0.96 [P_trend = .15]).

CONCLUSIONS:

Regular physical activity may reduce prostate cancer risk among black men, and activity during young adulthood may yield the greatest benefit. This novel finding needs confirmation in additional studies. Cancer 2009. Published 2009 by the American Cancer Society.     

Short- vs long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate

BACKGROUND

The study evaluated whether the use of 3 years as compared with 6 months of androgen suppression therapy (AST) combined with external beam radiation therapy (RT) in the treatment of high‐risk prostate cancer was associated with prolonged survival in advanced age men.

METHODS

A pooled analysis of 311 men enrolled in 3 prospective randomized trials between 1987 and 2000 who received 6 months or 3 years of AST and RT for locally advanced or high‐grade localized adenocarcinoma of the prostate comprised the study cohort. Cox regression multivariable analysis was performed adjusting for known prognostic factors to determine whether the treatment received was associated with time to death after randomization. The median age and follow‐up was 70 and 5.9 years, respectively, during which 82 (26%) deaths occurred.

RESULTS

Treatment received was not significantly associated with survival time after randomization (adjusted hazard ratio [AHR]: 1.1; 95% confidence interval [CI]: 0.7, 1.8; P = .70), whereas age at randomization (AHR: 1.05; 95% CI: 1.01, 1.09; P = .02) was. The presence of Gleason score 8 to 10 cancers approached significance (AHR: 1.6; 95% CI: 0.9, 2.6; P = .09).

CONCLUSIONS

After adjusting for known prognostic factors, the treatment of node‐negative, high‐risk prostate cancer using 3 years as compared with 6 months of AST with RT was not associated with prolonged survival in men of advanced age. The European Organization for Research and Treatment of Cancer randomized trial will help answer whether unknown confounding factors affected the results of the study. Cancer 2007. © 2007 American Cancer Society.     

Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of prostate-specific antigen at or before age 50

BACKGROUND:

We previously reported that a single prostate‐specific antigen (PSA) measured at ages 44‐50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow‐up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage ≥T3 or metastases at diagnosis).

METHODS:

Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974‐1986 at ages 33‐50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls.

RESULTS:

At a median follow‐up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% CI, 0.70‐0.74; for advanced cancer, 0.75; 95% CI, 0.72‐0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% CI, 77%‐86%) found in men with PSA above the median (0.63 ng/mL at ages 44‐50).

CONCLUSIONS:

A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low‐risk men to be screened less often but increase frequency of testing on a more limited number of high‐risk men. This is likely to improve the ratio of benefit to harm for screening. Cancer 2011. © 2010 American Cancer Society.     

Causes of death in men undergoing androgen suppression therapy for newly diagnosed localized or recurrent prostate cancer

BACKGROUND.

The authors estimated and characterized mortality after androgen suppression therapy (AST) use in men with newly diagnosed localized and recurrent prostate cancer.

METHODS.

The study cohorts comprised 102 men who were randomized to radiation therapy (RT) and AST and 46 men who underwent salvage AST for recurrence from a randomized trial that compared external beam RT and 6 months of AST to RT. Cox regression multivariable analyses were performed to estimate the mortality hazard ratio (HR) in men with moderate to severe as compared with no or minimal comorbidity, adjusting for age and known prostate cancer prognostic factors.

RESULTS.

After a median follow‐up of 8.4 years (interquartile range: 7.2‐9.6 years), prostate cancer‐specific mortality (PCSM) comprised 13% and 75% of all mortality in men with newly diagnosed localized and recurrent prostate cancer, respectively. There was an increased risk of death in men with moderate to severe as compared with no or minimal comorbidity (adjusted HR [AHR], 11.5; 95% confidence interval [CI], 5.2‐25.6; P < .001) in men with newly diagnosed localized prostate cancer but not in men with recurrent prostate cancer (AHR, 2.5; 95% CI, 0.2‐37.8; P = .51).

CONCLUSIONS.

The ability to measure an increase in the risk of death in men with moderate to severe as compared with no or minimal comorbidity undergoing AST decreases as the risk of PCSM increases, which may explain the discordance in the literature regarding the risk of cardiovascular death and AST use. Cancer 2008. © 2008 American Cancer Society.     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

Treatment and survival outcomes in young men diagnosed with prostate cancer

BACKGROUND:

Outcomes of treatment for young men compared with older men with prostate cancer are poorly defined outside of limited institutional series. In this study, the authors examined the association between age at diagnosis and grade, stage, treatment, and survival outcomes in men who were diagnosed during the era of prostate‐specific antigen testing.

METHODS:

The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify men who were diagnosed with prostate cancer between 1988 and 2003. Men ages 35 years to 74 years were stratified by age at diagnosis to examine differences in tumor characteristics, treatment, and survival within each age group.

RESULTS:

In total, 318,774 men ages 35 years to 74 years were identified who had been diagnosed with adenocarcinoma of the prostate between 1988 and 2003. The proportion of men aged ≤55 years at diagnosis increased over the study period from 2.3% between the years 1988 and 1991 to 9% between the years 2000 and 2003, and the median age at diagnosis decreased from 72 years in 1988 to 68 years in 2003. Younger men were diagnosed less frequently with organ‐confined tumors (P < .001) but were less likely to be diagnosed with high‐grade cancer (P < .001). Older men were more likely to receive no local therapy or external beam radiation than young men (P < .001 for trend). Among men who had tumors with a Gleason score between 5 and 7, overall survival was worse with advancing age. However, among all age groups with high grade and stage, the youngest men (ages 35‐44 years) were at the highest risk of all‐cause and cancer‐specific death.

CONCLUSIONS:

Age at diagnosis among men with prostate cancer continued to decline. Younger men were more likely to undergo prostatectomy, have lower grade cancer, and, as a group, to have better overall and equivalent cancer‐specific survival at 10 years compared with older men. Among men with high grade and locally advanced prostate cancer, the youngest men had a particularly poor prognosis compared with older men. Cancer 2009. Published 2009 by the American Cancer Society.     

Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

Bone density testing among prostate cancer survivors treated with androgen‐deprivation therapy

BACKGROUND.

Androgen‐deprivation therapy (ADT) causes bone loss and fractures. Guidelines recommend bone density testing before and during ADT to characterize fracture risk. The authors of the current report assessed bone density testing among men who received ADT for ≥ 1 year.

METHODS.

Surveillance, Epidemiology, and End Results/Medicare data were used to identify 28,960 men aged > 65 years with local/regional prostate cancer diagnosed from 2001 to 2007 who were followed through 2009 and who received ≥ 1 year of continuous ADT. Bone density testing was documented in the 18‐month period beginning 6 months before ADT initiation. Logistic regression was used to identify the factors associated with bone density testing.

RESULTS.

Among men who received ≥ 1 year of ADT, 10.2% had a bone density assessment from 6 months before starting ADT through 1 year after. Bone density testing increased over time (14.5% of men who initiated ADT in 2007‐2008 vs 6% of men who initiated ADT in 2001‐2002; odds ratio for 2007‐2008 vs 2001‐2002, 2.29; 95% confidence interval, 1.83‐2.85). Less bone density testing was observed among men aged ≥ 85 years versus men ages 66 to 69 years (odds ratio, 0.76; 95% confidence interval, 0.65‐0.89), among black men versus white men (odds ratio, 0.72; 95% confidence interval, 0.61‐0.86), and among men in areas with lower educational attainment (P < .001). Men who visited a medical oncologist and/or a primary care provider in addition to a urologist had higher odds of testing than men who only consulted a urologist (P < .001).

CONCLUSIONS.

Few men who received ADT for prostate cancer underwent bone density testing, particularly older men, black men, and those living in areas with low educational attainment. Visiting a medical oncologist was associated with increased odds of testing. Interventions are needed to increase bone density testing among men who receive long‐term ADT. Data on bone density testing for nonmilitary populations of prostate cancer survivors in the United States who have received long‐term androgen‐deprivation therapy (ADT) have not been published. The current analysis of Surveillance, Epidemiology, and End Results/Medicare data suggests that few prostate cancer survivors who receive long‐term ADT undergo bone density testing; and several key populations, including African Americans and older men, have considerably lower rates of bone density screening. Cancer 2013. © 2012 American Cancer Society.     

Why are pretreatment prostate‐specific antigen levels and biochemical recurrence poor predictors of prostate cancer survival?

BACKGROUND:

The value of pretreatment (initial) prostate‐specific antigen (iPSA) and biochemical recurrence (BR) as prognostic factors for survival remains unclear. The authors sought to determine why using randomized trial data with 7‐year minimum follow‐up.

METHODS:

In the Trans‐Tasman Radiation Oncology Group 96.01 trial, 802 men with T2b, T2c, T3, or T4 N0 prostate cancer (PC) were randomized to radiotherapy alone or with 3 or 6 months neoadjuvant androgen deprivation between 1996 and 2000. Cox modeling was used to identify outcome predictors at follow‐up landmark points.

RESULTS:

Higher iPSA was found to be a potent predictor of BR–free survival (P < .01) but was not prognostic for prostate cancer–specific survival (PCSS) from randomization. Patients experiencing BR had unfavorable initial prognostic factors compared with patients who did not. After BR, these factors were not prognostic for PC death in models adjusted for time to BR (TTBR). In these models, TTBR predicted PCSS more satisfactorily than the occurrence of BR itself. Survival probability 5 years after BR exceeded 90% for men with TTBR ≥4 years; however, it dropped to 44% ± 6% for men with TTBR <1 year. After BR, rapid PSA doubling time (DT), low iPSA, and short TTBR were identified as the most important predictors of inferior PCSS.

CONCLUSIONS:

When BR occurs, prognostic factors for survival change. Low iPSA, short TTBR, and rapid PSA DT take over at this point, providing reasons why iPSA and occurrence of BR alone predict PCSS unsatisfactorily. Cancer 2009. © 2009 American Cancer Society.     

Patient‐reported outcomes after 3‐dimensional conformal,intensity‐modulated,or proton beam radiotherapy for localized prostate cancer

BACKGROUND:

Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3‐dimensional conformal radiotherapy (3DCRT), intensity‐modulated radiotherapy (IMRT), or proton beam therapy (PBT).

METHODS:

The authors reviewed patient‐reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the baseline mean value. Changes from baseline were compared within groups at the first post‐treatment follow‐up (2‐3 months from the start of treatment) and at 12 months and 24 months.

RESULTS:

At the first post‐treatment follow‐up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post‐treatment follow‐up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL.

CONCLUSIONS:

Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment‐related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences. Cancer 2013. © 2013 American Cancer Society.     

Alcohol consumption,finasteride, and prostate cancer risk

BACKGROUND:

Current research is inconclusive regarding the relation between alcohol consumption and prostate cancer risk. In this study, the authors examined the associations of total alcohol, type of alcoholic beverage, and drinking pattern with the risk of total, low‐grade, and high‐grade prostate cancer.

METHODS:

Data for this study came from the 2129 participants in the Prostate Cancer Prevention Trial (PCPT) who had cancer detected during the 7‐year trial and 8791 men who were determined by biopsy to be free of cancer at the trial end. Poisson regression was used to calculate relative risks (RRs) and 95% confidence intervals (95% CIs) for associations of alcohol intake with prostate cancer risk.

RESULTS:

Associations of drinking with high‐grade disease did not differ by treatment arm. In combined arms, heavy alcohol consumption (≥50 g of alcohol daily) and regular heavy drinking (≥4 drinks daily on ≥5 days per week) were associated with increased risks of high‐grade prostate cancer (RR, 2.01 [95% CI, 1.33‐3.05] and 2.17 [95% CI, 1.42‐3.30], respectively); less heavy drinking was not associated with risk. Associations of drinking with low‐grade cancer differed by treatment arm. In the placebo arm, there was no association of drinking with risk of low‐grade cancer. In the finasteride arm, drinking ≥50 g of alcohol daily was associated with an increased risk of low‐grade disease (RR, 1.89; 95% CI, 1.39‐2.56); this finding was because of a 43% reduction in the risk of low‐grade cancer attributable to finasteride treatment in men who drank <50g of alcohol daily and the lack of an effect of finasteride in men who drank ≥50 g of alcohol daily (P_interaction = .03).

CONCLUSIONS:

Heavy, daily drinking increased the risk of high‐grade prostate cancer. Heavy drinking made finasteride ineffective for reducing prostate cancer risk. Cancer 2009. © 2009 American Cancer Society.