Hormonal therapy or external-beam radiation with brachytherapy and the risk of death from prostate cancer in men with intermediate risk prostate cancer

Purpose

To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy.

Patients and Methods

A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer-specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category.

Results

Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively).

Conclusion

Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.     

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.     

Survival Outcomes of Radical Prostatectomy Versus Radiotherapy in Intermediate-Risk Prostate Cancer: A NCDB Study

Background

Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment.

Utilization and expense of adjuvant cancer therapies following radical prostatectomy

BACKGROUND:

We sought to identify the costs of adjuvant therapies following radical prostatectomy (RP) and factors associated with their receipt.

METHODS:

We used SEER‐Medicare data from 2004‐2006 to identify 4247 men who underwent RP, of whom 600 subsequently received adjuvant therapies. We used Cox regression to identify factors associated with receipt of adjuvant therapies. Health care expenditures within 12 months of diagnosis were compared for RP alone versus RP with adjuvant therapies.

RESULTS:

Biopsy Gleason score, prostate‐specific antigen, risk group, and SEER region were significantly associated with receipt of adjuvant treatments (all P<.001). Higher surgeon volume was associated with lower odds of receiving adjuvant therapies (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46‐0.78 [P<.001]). Factors associated with increased receipt of adjuvant therapies were positive surgical margins (HR, 3.02; 95% CI, 2.55‐3.57 [P<.001]), high‐risk group versus low‐risk group (HR, 7.65; 95% CI, 5.64‐10.37 [P<.001]), lymph node–positive disease (HR, 5.36; 95% CI, 3.71‐7.75 [P<.001]), and treatment in Iowa (HR, 1.93; 95% CI, 1.12‐3.32 [P = .019]) and New Mexico/Georgia/Hawaii (HR, 1.92; 95% CI, 1.09‐3.39 [P = .025]) versus San Francisco SEER regions (baseline). Age, race, comorbidities, and surgical approach were not associated with use of adjuvant therapies. The median expenditures attributable to postprostatectomy hormonal therapy, radiation therapy, and radiation with hormonal therapy versus were $1361, $12,040, and $23,487.

CONCLUSIONS:

Men treated by high‐volume surgeons were less likely to receive adjuvant therapies. Regional variation and high‐risk disease characteristics were associated with increased receipt of adjuvant therapies, which increased health care expenditures by 2‐ to 3‐fold when radiotherapy was administered. Cancer 2011. © 2011 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.     

Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database

Purpose

To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.

Statin medication use and the risk of biochemical recurrence after radical prostatectomy

BACKGROUND:

Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate‐specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP).

METHODS:

The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features.

RESULTS:

In total, 236 (18%) men were taking statins at RP. Median follow‐up was 24 months for statin users and 38 for nonusers. Statin users were older (P < .001) and underwent RP more recently (P < .001). Statin users were diagnosed at lower clinical stages (P = .009) and with lower PSA levels (P = .04). However, statin users tended to have higher biopsy Gleason scores (P = .002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio “HR”, 0.70; 95% confidence interval “CI”, 0.50‐0.97; P = .03), which was dose dependent (relative to no statin use; dose equivalent<simvastatin 20 mg: HR, 1.08; 95% CI, 0.66‐1.73; P = .78; dose equivalent = simvastatin 20 mg: HR, 0.57; 95% CI, 0.32‐1.00; P = .05; dose equivalent>simvastatin 20 mg: HR, 0.50; 95% CI, 0.27‐0.93; P = .03).

CONCLUSIONS:

In this cohort of men undergoing RP, statin use was associated with a dose‐dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP. Cancer 2010. © 2010 American Cancer Society.     

Interval to biochemical failure as a biomarker for cause-specific and overall survival after dose-escalated external beam radiation therapy for prostate cancer

BACKGROUND:

After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT.

METHODS:

From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated.

RESULTS:

There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS (P < .0001) but not OS (P = .36). However, a short interval to biochemical failure predicted decreased CSS (P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS (P < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure (P = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure (P < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death (P < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality (P = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not.

CONCLUSIONS:

The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 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.     

Comparison of Surgery and Radiation as Local Treatments in the Risk of Locoregional Complications in Men Subsequently Dying From Prostate Cancer

Introduction

Late locoregional complications in prostate cancer (PCa) affect quality of life and require medical interventions. Our objective was to compare late locoregional complications in men dying of castration-resistant PCa (CRPC) who previously received external-beam radiotherapy (EBRT) to radical prostatectomy (RP). No group without previous primary local treatment was included.

Cancer-specific mortality after radiation therapy with short-course hormonal therapy or radical prostatectomy in men with localized, intermediate-risk to high-risk prostate cancer

BACKGROUND: The presence of multiple determinants of aggressive cancer biology may impact prostate cancer-specific mortality (PCSM) rates compared with fewer factors. The authors estimated PCSM after radiation therapy with short-course androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with clinically localized, intermediate-risk to high-risk prostate cancer. METHODS: The study cohort included 3240 men treated from 1981 to 2002 with RT with 6 months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason score 7-10, or clinical tumor category T2b or T2c). Competing risks regression analyses were used to determine whether the number of risk factors present was associated with time to PCSM. RESULTS: Men with all 3 risk factors had significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of 9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1 or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95% CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of intermediate-risk to high-risk prostate cancer have significantly increased estimates of PCSM despite aggressive therapy compared with men with only 1 or 2 determinants. These men are appropriate candidates for enrollment onto randomized controlled trials evaluating the benefit of adding systemic therapies such as docetaxel to RT+AST or RP.     

Coronary revascularization and mortality in men with congestive heart failure or prior myocardial infarction who receive androgen deprivation

BACKGROUND:

A study was undertaken to determine the impact of prior coronary revascularization (angioplasty, stent, or coronary artery bypass graft) on the risk of all‐cause mortality after neoadjuvant hormonal therapy (HT) for prostate cancer (PC) in men with a history of coronary artery disease (CAD)‐induced congestive heart failure (CHF) or myocardial infarction (MI).

METHODS:

Among 7839 men who received radiation with or without a median of 4 months of HT for PC from 1991 to 2006, 495 (6.3%) had CAD‐induced CHF or MI and formed the study cohort. Of these men, 250 (50.5%) had been revascularized before treatment for PC. Cox regression was used to determine whether HT increased the risk of all‐cause mortality, and whether revascularization altered this risk, after adjusting for known PC prognostic factors and a propensity score for revascularization.

RESULTS:

Median follow‐up was 4.1 years. Neoadjuvant HT was associated with an increased risk of all‐cause mortality (28.9% vs 15.7% at 5 years; adjusted hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.13‐2.64; P = .01). Men who received HT without revascularization had the highest risk of all‐cause mortality (33.3%; adjusted HR, 1.48; 95% CI, 1.01‐2.18; P = .047), whereas men who were revascularized and did not receive HT had the lowest risk of all‐cause mortality (9.4%; adjusted HR, 0.51; 95% CI, 0.28‐0.93; P = .028). The reference group had an intermediate risk of all‐cause mortality (23.4%) and was comprised of men in whom HT use and revascularization were either both given or both withheld.

CONCLUSIONS:

In men with a history of CAD‐induced CHF or MI, neoadjuvant HT is associated with an excess risk of mortality, which appears to be reduced but not eliminated by prior revascularization. Cancer 2011. © 2010 American Cancer Society.     

The quantitative Gleason score improves prostate cancer risk assessment

BACKGROUND:

In the current study, the authors propose the quantitative Gleason score (qGS), a modification of the current Gleason grading system for prostate cancer, based on the weighted average of Gleason patterns present in the pathology specimen. They hypothesize that the qGS can improve prostate cancer risk stratification and help prevent the overtreatment of patients with clinically indolent tumors.

METHODS:

The qGS was applied to patients in the University of California San Francisco urologic oncology database with tumors determined to have a GS of 7 on prostate biopsy or final pathology after radical prostatectomy (RP). Using multivariable logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC), and decision curve analyses, the ability of qGS to predict pathological GS and the risk of disease recurrence after RP was assessed.

RESULTS:

A total of 225 men were included in the analysis of biopsy specimens and 618 men were included in the assessment of RP specimens. Compared with traditional Gleason scoring, the qGS improved concordance between biopsy and pathological GS on decision curve and ROC analyses (area under the curve ROC curve, 0.79 vs 0.71). On regression analysis, the qGS of biopsy specimens was found to be significantly associated with pathological grade after RP (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.49‐2.12) and the qGS of RP specimens was significantly associated with the risk of biochemical disease recurrence after RP (HR, 1.13; 95% CI, 1.04‐1.24).

CONCLUSIONS:

The qGS, a simple modification of the current Gleason system, appears to improve the correlation between biopsy and pathological GS, as well as the prediction of biochemical disease recurrence after RP. This scoring system may allow more men to pursue active surveillance, thereby avoiding the morbidity of prostate cancer treatment modalities. Cancer 2012. © 2012 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.     

Secondary sarcomas after radiotherapy for breast cancer

BACKGROUND:

Radiotherapy (RT) has been a risk factor for development of soft tissue sarcomas (STS). The objective of the current study was to quantify the risk of STS after RT and surgery for breast cancer (BCa), assess time trends, and compare long‐term survival of patients with RT‐associated and non–RT‐associated angiosarcoma (AS) using the Surveillance, Epidemiology, and End Results (SEER) database.

METHODS:

Women with BCa reported to SEER in 1973 to 2003 were included. Kaplan‐Meier curves and proportional hazards models, reported as hazards ratios (HR) with 95% confidence intervals (95% CI), were used. Survival of patients who developed RT‐associated AS was compared with that of patients with primary AS of the thorax and upper extremities.

RESULTS:

The cohort of 563,155 BCa patients was divided into 2 groups: those who received RT (37%) and those who received no RT. RT use increased with time (P <. 0001). A total of 948 patients developed STS 1 to 29 years after BCa diagnosis. RT patients had a higher incidence of all STS (31 vs 22 per 100,000 person‐years; HR, 1.5 [95%CI, 1.3‐1.8]), AS (HR, 7.6; 95% CI, 4.9‐11.9), and malignant fibrous histiocytomas (MFH) (HR, 2.5; 95% CI, 1.6‐3.9). RT remained a significant predictor after adjustment for covariates (HR, 1.4; 95% CI, 1.2‐1.7). Partial mastectomies (HR, 7.1; 95% CI, 3.2‐16), RT (HR, 2.2; 95% CI, 1.1‐4.3), and lymph node dissections (HR, 2.6; 95% CI, 1.3‐5) were found to be independent risk factors for AS. The hazard of STS after RT peaked at 10 years, reaching the non‐RT hazard at approximately 23 years. The 5‐year survival for STS was 38%. There was no difference in survival noted between RT‐induced and non–RT‐induced AS.

CONCLUSIONS:

RT was found to increase the risk for STS, in particular AS and MFH. Patients who received RT for BCa should be followed closely for >20 years. Cancer 2009. © 2009 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.     

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors

BACKGROUND: Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. METHODS: The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. RESULTS: Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. CONCLUSIONS: Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC.     

Pooled cohort study on height and risk of cancer and cancer death

Purpose

To assess the association between height and risk of cancer and cancer death.

Methods

The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model.

Results

During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06–1.09), and in men, HR 1.04 (95 % CI 1.03–1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11–1.24), and in men HR 1.12 (95 % CI 1.08–1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01–1.16), and in men, HR 1.03 (95 % CI 1.01–1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00–1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07–1.30). All these associations were independent of body mass index.

Conclusion

Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.     

Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer.

PURPOSE: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density, a surrogate for fracture risk, in men with prostate cancer. We conducted a claims-based cohort study to characterize the relationship between GnRH agonists and risk for clinical fractures in men with nonmetastatic prostate cancer. PATIENTS AND METHODS: Using medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group of men with nonmetastatic prostate cancer who initiated GnRH agonist treatment from 1992 to 1994 (n = 3,887). A comparison group of men with nonmetastatic prostate cancer who did not receive GnRH agonist treatment during the study period (n = 7,774) was matched for age, race, geographic location, and comorbidity. Clinical fractures were identified using inpatient, outpatient, and physician claims during 7 years of follow-up. RESULTS: In men with nonmetastatic prostate cancer, GnRH agonists significantly increased fracture risk. The rate of any clinical fracture was 7.88 per 100 person-years at risk in men receiving a GnRH agonist compared with 6.51 per 100 person-years in matched controls (relative risk, 1.21; 95% CI, 1.14 to 1.29; P < .001). Rates of vertebral fractures (relative risk, 1.45; 95% CI, 1.19 to 1.75; P < .001) and hip/femur fractures (relative risk, 1.30; 95% CI, 1.10 to 1.53; P = .002) were also significantly higher in men who received a GnRH agonist. GnRH agonist treatment independently predicted fracture risk in multivariate analyses. Longer duration of treatment conferred greater fracture risk. CONCLUSION: GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer.