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.     

Impact of androgen deprivation on physical well-being in patients with prostate cancer: analysis from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry

BACKGROUND:

As androgen deprivation therapy (ADT) becomes a standard of treatment for men with recurrent or metastatic prostate cancer, evaluation of adverse effects associated with this treatment is needed. In this study, the authors evaluated the effect of ADT administered as monotherapy and in combination with local treatment on physical well‐being in a longitudinal sample of men with prostate cancer.

METHODS:

Exposure to ADT was defined by 3 groups: local (local treatment only), combination (local treatment with adjuvant and/or neoadjuvant ADT), and primary ADT. Associations between exposure to ADT and physical well‐being measured by self‐reported health‐related quality of life outcomes over time were evaluated by repeated measures analysis using mixed modeling. Estimates adjusted for various clinical and demographic variables are reported.

RESULTS:

A total of 2922 men, who completed both pretreatment and follow‐up health‐related quality of life assessment, were identified from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. During 24 months of follow‐up, exposure to ADT was associated with worse physical well‐being compared with local treatment at all time points (P < .001). Being exposed to ADT as primary therapy was associated with more severe declines compared with combination therapy.

CONCLUSIONS:

The potential consequence of decline in physical well‐being in patients exposed to ADT has to be included in treatment decision making. Cancer 2011;. © 2011 American Cancer Society.     

Androgen deprivation and thromboembolic events in men with prostate cancer

BACKGROUND:

Androgen deprivation therapy (ADT) improves prostate cancer outcomes in specific clinical settings, but is associated with adverse effects, including cardiac complications and possibly thromboembolic complications. The objective of this study was to estimate the impact of ADT on thromboembolic events (TEs) in a population‐based cohort.

METHODS:

In the linked Surveillance, Epidemiology and End Results–Medicare database, we identified men older than 65 who were diagnosed with nonmetastatic prostate cancer between 1999 and 2005. Medical or surgical ADT was identified by Medicare claims for gonadotropin‐releasing hormone agonists or bilateral orchiectomy at any time following diagnosis. TEs included deep venous thrombosis, pulmonary embolism, and arterial embolism. The impact of ADT on the risk of any TE and on total number of events was estimated, controlling for patient and tumor characteristics.

RESULTS:

Of 154,611 patients with prostate cancer, 58,466 (38%) received ADT. During a median follow‐up of 52 months, 15,950 men had at least 1 TE, including 8829 (55%) who had ADT and 7121 (45%) with no ADT. ADT was associated with increased risk of a TE (adjusted hazard ratio = 1.56; 95% confidence interval, 1.50‐1.61; P < .0001), and duration of ADT was associated with the total number of events (P < .0001).

CONCLUSIONS:

In this population‐based cohort, ADT was associated with increased risk of a TE, and longer durations of ADT were associated with more TEs. Men with intermediate‐ and low‐risk prostate cancer should be assessed for TE risk factors before starting ADT and counseled regarding the risks and benefits of this therapy. 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.     

Impact of race on biochemical disease recurrence after prostate brachytherapy

BACKGROUND:

Understanding racial differences in disease presentation and response to therapy is necessary for the effective treatment and control of prostate cancer. In this study, the authors examined the influence of race on biochemical disease‐free survival (BDFS) among men who received prostate brachytherapy.

METHODS:

In total, 2301 men were identified who had a minimum follow‐up of 24 months and had received low‐dose‐rate brachytherapy for prostate cancer at the Mount Sinai Medical Center from June 1990 to October 2008. Patient factors, with specific emphasis on patient race, were analyzed with respect to freedom from biochemical failure (FFbF). Kaplan‐Meier analyses, life‐tables, and log‐rank tests were used to identify variables that were predictive of 10‐year FFbF.

RESULTS:

In this series, a total of 2268 patients included 81% Caucasians, 12% African Americans, 6% Hispanics, and 1% Asians. The 10‐year actuarial FFbF rate was 70% for AA men and 84% for all others (P = .002). Between Caucasian men and AA men, the 10‐year FFbF rate was 83% versus 70%, respectively (P = .001).There was no significant difference in 10‐year FFbF between Caucasian men and Hispanic men (83% vs 86%, respectively; P = .6). The 10‐year FFbF rate for Hispanic men and AA men was 86% versus 70%, respectively (P = .062). A greater percentage of AA men presented with higher prostate‐specific antigen levels (PSA) (>10 ng/mL; 44% vs 21%; P < .001) and, thus, with higher risk disease (24% vs 15%; P < .001) compared with Caucasian men. Among the men with low‐risk disease, the 10‐year FFbF rate was 90% for Caucasian men and 76% for AA men (P = .041). The 10‐year BDFS rate for patients who received brachytherapy alone was 86% for Caucasian men and 61% for AA men (P = .001); however, this difference was not observed when brachytherapy was combined with androgen‐deprivation therapy(ADT) with or without supplemental external‐beam radiotherapy (EBRT). Multivariate analysis revealed that PSA (P = .024), Gleason score (P < .001), the biologic effective dose (P < .001), EBRT (P = .002), ADT (P = .03), and AA race (P = .037) were significant predictors of 10‐year FFbF. No significant differences was observed in overall survival, cause‐specific survival, or distant metastasis‐free survival between racial groups.

CONCLUSIONS:

AA race appeared to be an independent negative predictor of BDFS after prostate brachytherapy, and this result may highlight the need for more aggressive therapy in this patient population. Cancer 2011;. © 2011 American Cancer Society.     

Single infusion of zoledronic acid to prevent androgen deprivation therapy‐induced bone loss in men with hormone‐naive prostate carcinoma

BACKGROUND:

Androgen‐deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone‐naive prostate carcinoma.

METHODS:

Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual‐energy x‐ray absorptiometry and urinary N‐telopeptide (u‐NTx) at 6 and 12 months.

RESULTS:

At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6months, mean (±standard error) BMD of the posteroanterior lumbar spine decreased 4.6% ± 1.0% in control patients and increased 5.1% ± 1.2% in patients receiving zoledronic acid, a significant difference (P = .0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P = .0004), indicating that zoledronate preserved BMD. For u‐NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P < .0001), but returned to pretreatment levels at 12 months in the zoledronate group.

CONCLUSIONS:

Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT‐induced bone loss in men with hormone‐naive prostate carcinoma. Cancer 2009. © 2009 American Cancer Society.     

Population‐based 10‐year oncologic outcomes after low‐dose‐rate brachytherapy for low‐risk and intermediate‐risk prostate cancer

BACKGROUND.

The objective of this study was to report the rates of disease‐free survival (DFS), cause‐specific survival (CSS), and overall survival after low‐dose‐rate (LDR) prostate brachytherapy (PB).

METHODS.

Data from 1006 consecutive patients with prostate cancer who received LDR‐PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low‐risk (58%) or intermediate‐risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty‐five percent of patients received 3 months of neoadjuvant androgen‐deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables.

RESULTS.

The median follow‐up was 7.5 years. By using Fine and Gray competing risks analysis, the 5‐year and 10‐year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%‐97.7%) and 94.1% (95% confidence interval, 92%‐95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10‐year CSS rate was 99.1% (95% confidence interval, 97.3%‐99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%‐95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%‐86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis.

CONCLUSIONS.

In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low‐risk and intermediate‐risk prostate cancer, the actuarial rate of recurrent disease after LDR‐PB was approximately 3% at 5 years and 6% at 10 years. Cancer 2013. © 2012 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.     

Time to prostate‐specific antigen nadir independently predicts overall survival in patients who have metastatic hormone‐sensitive prostate cancer treated with androgen‐deprivation therapy

BACKGROUND:

The objective of this study was to evaluate the relation between the kinetics of prostate‐specific antigen (PSA) decline after the initiation of androgen‐deprivation therapy (ADT) and overall survival (OS) in men with metastatic, hormone‐sensitive prostate cancer (HSPC).

METHODS:

The authors' institutional database was used to identify a cohort of men with metastatic HSPC who were treated with ADT. Patients were included if they had at least 2 serum PSA determinations before PSA nadir and at least 1 serum PSA value available within 1 month of ADT initiation. Patient characteristics, PSA at ADT initiation, nadir PSA, time to PSA nadir (TTN), and PSA decline (PSAD) in relation to OS were analyzed.

RESULTS:

One hundred seventy‐nine patients were identified, and they had a median follow‐up after ADT initiation of 4 years. The median OS after ADT initiation was 7 years. The median PSA level at ADT initiation and PSA nadir were 47 ng/mL and 0.28 ng/mL, respectively. On univariate analysis: TTN <6 months, PSAD >52 ng/mL per year, PSA nadir ≥0.2 ng/mL, PSA ≥47.2 ng/mL at ADT initiation, and Gleason score >7 were associated with shorter OS. On multivariate analysis, TTN <6 months, Gleason score >7, and PSA nadir ≥0.2 ng/mL independently predicted shorter OS.

CONCLUSIONS:

To the authors' knowledge, this was the first report to demonstrate that a faster time to reach a PSA nadir after the initiation of ADT was associated with shorter survival duration in men with metastatic HSPC. These results need confirmation but may indicate that a rapid initial response to ADT indicates more aggressive disease. Cancer 2009. © 2009 American Cancer Society.     

Impact of androgen deprivation therapy on depressive symptoms in men with nonmetastatic prostate cancer

BACKGROUND:

Up to 50% of prostate cancer (PC) patients receive androgen deprivation therapy (ADT), often for several years. Although depression has been reported after a diagnosis of PC, whether ADT leads to or worsens depression is not clear.

METHODS:

Three groups were assembled: ADT users (men initiating continuous ADT), PC controls (PC patients who were not on ADT), and healthy controls. All 3 cohorts were matched on age, education, and physical function, and none had metastases. Depression was measured at study entry and again at 3, 6, and 12 months using the 15‐item Geriatric Depression Scale (GDS). Our primary outcomes were worsening depressive symptoms and incident depression (defined as a GDS score ≥5), analyzed using adjusted linear regression and logistic regression, respectively.

RESULTS:

Of the 257 participants (mean age, 69.1 years), baseline characteristics including GDS score and prior depression were similar across cohorts. In adjusted analyses of initially nondepressed patients, ADT use was not a significant predictor of change in GDS score at 3 months (P = .42), 6 months (P = .25), or 12 months (P = 0.19). Among ADT users, 8%‐9% of participants developed incident depression compared with 0%‐4% among PC controls and 4%‐6% among healthy controls over 3‐12 months (P>.05 at all time points). In a separate analysis of patients with depression at baseline, there was no effect of ADT on depressive symptoms at 3, 6, or 12 months (P = .11, .74, and .12, respectively).

CONCLUSION:

Twelve months of ADT use were not associated with worsening depressive symptoms among nondepressed or depressed patients with nonmetastatic PC. Cancer 2012;. © 2011 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.     

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.     

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.     

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.

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.     

Elective irradiation of pelvic lymph nodes during postprostatectomy salvage radiotherapy

BACKGROUND:

Success rates with salvage radiotherapy (SRT) in men who have a postprostatectomy biochemical relapse are suboptimal. One treatment‐intensification strategy includes elective irradiation of the pelvic lymph nodes with whole pelvis radiotherapy (WPRT).

METHODS:

An inter‐institutional retrospective cohort study compared outcomes for patients who received SRT at 2 separate academic institutions with disparate treatment paradigms: almost exclusively favoring WPRT (n = 112) versus limiting treatment to the prostate bed (PBRT) (n = 135). Patients were excluded if they had lymph node involvement or if they received androgen‐deprivation therapy. The Cox proportional hazards model was used to adjust for potential confounders.

RESULTS:

In total, 247 patients were analyzed with a median follow‐up of 4 years. The pre‐SRT prostate‐specific antigen (PSA) level (adjusted hazard ratio [HR], 1.58; P < .0001) and a Gleason score of 8 to 10 (adjusted HR, 3.21; P < .0001) were identified as independent predictors of increased risk of biochemical PSA progression after SRT. However, WPRT was not independently associated with biochemical progression‐free survival in the multivariate model (adjusted HR, 0.79; P = .20). Neither low‐risk patients nor high‐risk patients (defined a priori by a preoperative PSA level ≥20 ng/mL, a pathologic Gleason score between 8 and 10, or pathologic T3 tumor classification) benefited from WPRT. Overall survival was similar between treatment groups. When restricting the analysis to patients with pre‐SRT PSA levels ≥0.4 ng/mL (n = 139), WPRT was independently associated with a 53% reduction in the risk of biochemical progression (adjusted HR, 0.47; P = .031).

CONCLUSIONS:

WPRT did not improve outcomes among the entire group but was independently associated with improved biochemical control among patients with pre‐SRT PSA levels ≥0.4 ng/mL. Cancer 2013. © 2012 American Cancer Society.     

Should docetaxel be standard of care for patients with metastatic hormone-sensitive prostate cancer? Pro and contra

Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to men with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of patient survival. The GETUG-AFU-15 and CHAARTED studies both assessed the efficacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in men with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (∼75%) and patients who developed metastases following treatment of localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUG-AFU-15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to nine cycles; CHAARTED six cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT versus ADT alone. The GETUG-AFU-15 did not find a significant difference in the primary end point of overall survival (OS) {hazard ratio (HR) 0.9 [95% confidence interval (CI) 0.7–1.2]; P = 0.44} for ADT plus docetaxel versus ADT alone. The CHAARTED study met the primary end point of OS [HR 0.61 (95% CI 0.47–0.80); P = 0.0003], and in a subset analysis reported the greatest improvement in OS for patients with high-volume disease [HR 0.60 (95% CI 0.45–0.81); P = 0.0006]. The following article debates the results from the GETUG-AFU-15 and CHAARTED studies and asks whether medical practice should be changed for patients with metastatic hormone-naive prostate cancer based on the results of one positive study.     

Gemcitabine and docetaxel in metastatic, castrate-resistant prostate cancer: results from a phase 2 trial

BACKGROUND:

Docetaxel is the standard of care for patients with metastatic, castrate‐resistant prostate cancer (CRPC). Gemcitabine is a nucleoside analogue with broad antitumor activity. In a phase 2 study of combined docetaxel and gemcitabine, the authors assessed its safety and activity in patients with chemotherapy‐naive, metastatic CRPC.

METHODS:

Eligible patients had untreated, metastatic CRPC with radiologic and/or biochemical evidence of progression after antiandrogen withdrawal with castrate testosterone levels, an Eastern Cooperative Oncology performance status (ECOG PS) of 0 to 2, and adequate organ function; no previous chemotherapy was permitted. Patients received gemcitabine (800 mg/m²) Days 1 and 8 and docetaxel (75 mg/m²) on Day 8 every 21 days for a maximum of 6 cycles. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) for measurable disease. A prostate‐specific antigen (PSA) response was defined as a decline ≥50% in baseline PSA level.

RESULTS:

Thirty‐five patients with chemotherapy‐naive, metastatic CRPC were enrolled. The median age was 67 years, and 60% of patients had an ECOG PS of 0. PSA responses were observed in 49% of patients. Among the patients who had measurable disease (n = 25), 3 patients (12%) had a confirmed, RECIST‐defined partial response (PR); 4 patients (16%) had an unconfirmed PR; and 15 patients (60%) achieved stable disease. The most common adverse events included grade 1 and 2 fatigue (69%), alopecia (80%), and nausea/vomiting (54%). No treatment‐related deaths were noted, but an unusually high incidence of grade 3 and 4 neutropenia was observed.

CONCLUSIONS:

The efficacy of combined gemcitabine and docetaxel in metastatic CRPC was similar to that observed with single‐agent docetaxel. In contrast to single‐agent docetaxel, the combination was moderately toxic and had an impact primarily on bone marrow reserve. Cancer 2011. © 2010 American Cancer Society.     

Number of primary melanomas is an independent predictor of survival in patients with metastatic melanoma

BACKGROUND:

A history of multiple primary melanomas (PMs) has been associated with improved survival in patients with early stage melanoma, but whether it also is correlated with survival in patients with metastatic melanoma is unknown. The authors sought to address the latter question in the current study.

METHODS:

Patients with metastatic melanoma diagnosed at the Melanoma Institute Australia between 1983 and 2008 were identified. Overall survival (OS) was calculated from date of first distant metastasis. Survival analysis was performed using the Kaplan‐Meier method, log‐rank tests, and multivariate Cox proportional hazards models.

RESULTS:

Of 2942 patients with metastatic melanoma, 2634 (89.5%) had 1 PM and 308 (10.5%) had >1 PM. Factors that were associated independently with shorter OS were site of metastasis, including the brain (hazard ratio [HR], 2.41; 95% confidence interval [CI], 2.07‐2.81; P < .001) and nonlung viscera (HR, 1.92; 95% CI, 1.67‐2.22; P < .001, vs lymph node/subcutaneous/soft tissue), age >60 years (HR, 1.23; 95% CI, 1.12‐1.36; P < .001), shorter disease‐free interval from PM to first distant metastasis (≤12 months vs >36 months: HR, 1.62; 95% CI, 1.39‐1.89; P < .001), and fewer PMs (1 vs >1; HR, 1.26; 95% CI, 1.08‐1.47; P = .004).

CONCLUSIONS:

A history of multiple PM was an independent predictor of improved survival for patients with metastatic melanoma. The results indicate that a history of multiple PMs should be incorporated into multivariate analyses of prognostic factors and treatment outcomes. Cancer 2012. © 2012 American Cancer Society.