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.     

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.     

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.     

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.     

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.     

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.     

The impact of dose‐escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms

BACKGROUND:

Randomized trials have demonstrated that escalated‐dose external‐beam radiotherapy (EDRT) is better than standard‐dose radiotherapy (SDRT) for patients with prostate cancer and that adding androgen‐deprivation therapy (ADT) to SDRT is better than SDRT alone; however, no trials have compared EDRT versus SDRT plus ADT or EDRT versus EDRT plus ADT. The authors designed a model to estimate the results of various doses of radiotherapy (RT) combined with various durations of ADT.

METHODS:

From 1989 to 2007, 3215 men consecutively received definitive EDRT with or without ADT. In total, 2012 patients had complete records available for creating the nomogram. The duration of ADT varied for patients who received no RT (n = 1562), ≤6 months of RT (n = 145), from >6 months to <24 months of RT (n = 140), and ≥24 months of RT (n = 165) with a median follow‐up of 65.7 months, 66.2 months, 60.1 months, and 63 months, respectively. The model included the following covariates: palpation T‐category, biopsy Gleason score, the percentage of tumor cells with a Gleason pattern of 4 or 5, the percentage of tumor tissue, initial pretreatment prostate‐specific antigen (PSA) level, ADT duration, and RT dose. Two nomograms, for outcomes with and without ADT, were created from a single competing‐risks model. Biochemical failure was defined as a rise in serum PSA of 2 ng/mL over the post‐treatment PSA nadir.

RESULTS:

According to the results from analyzing representative intermediate‐risk to high‐risk patient parameters, the gains from increasing the RT dose from 70 Gray (Gy) to 80 Gy were far less than the gains from adding ≥3 months of ADT.

CONCLUSIONS:

The nomograms provided unique patient‐specific estimates of the effects of various doses and durations of RT and ADT. The results indicated that adding ADT to treatment for intermediate‐risk and high‐risk prostate cancer is far more beneficial than a modest RT dose escalation. Cancer 2013. © 2012 American Cancer Society.     

Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer

BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS.: A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS.: Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.     

Radiation dose escalation for localized prostate cancer

BACKGROUND:

In the current study, the effects of dose escalation for localized prostate cancer treatment with intensity‐modulated radiotherapy (IMRT) or permanent transperineal brachytherapy (BRT) in comparison with conventional dose 3‐dimensional conformal radiotherapy (3D‐CRT) were evaluated.

METHODS:

This study included 853 patients; 270 received conventional dose 3D‐CRT, 314 received high‐dose IMRT, 225 received BRT, and 44 received external beam radiotherapy (EBRT) + BRT boost. The median radiation doses were 68.4 grays (Gy) for 3D‐CRT and 75.6 Gy for IMRT. BRT patients received a prescribed dose of 144 Gy with iodine‐125 (I‐125) or 120 Gy with palladium‐103 (Pd‐103), respectively. Patients treated with EBRT + BRT received 45 Gy of EBRT plus a boost of 110 Gy with I‐125 or 90 Gy with Pd‐103. Risk group categories were low risk (T1‐T2 disease, prostate‐specific antigen level ≤10 ng/mL, and a Gleason score ≤6), intermediate risk (increase in value of 1 of the factors), and high risk (increase in value of ≥2 factors).

RESULTS:

With a median follow‐up of 58 months, the 5‐year biochemical control (bNED) rates were 74% for 3D‐CRT, 87% for IMRT, 94% for BRT, and 94% for EBRT + BRT (P <.0001). For the intermediate‐risk group, high‐dose IMRT, BRT, or EBRT + BRT achieved significantly better bNED rates than 3D‐CRT (P <.0001), whereas no improvement was noted for the low‐risk group (P = .22). There was no increase in gastrointestinal (GI) toxicity from high‐dose IMRT compared with conventional dose 3D‐CRT, although there was more grade 2 genitourinary (GU) toxicity (toxicities were graded at the time of each follow‐up visit using a modified Radiation Therapy Oncology Group [RTOG] scale). BRT caused more GU but less GI toxicity, whereas EBRT + BRT caused more late GU and GI toxicity than IMRT or 3D‐CRT.

CONCLUSIONS:

The data from the current study indicate that radiation dose escalation improved the bNED rate for the intermediate‐risk group. IMRT caused less acute and late GU toxicity than BRT or EBRT + BRT. Cancer 2009. © 2009 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.     

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.     

Cancer‐specific mortality of high‐risk prostate cancer after carbon‐ion radiotherapy plus long‐term androgen deprivation therapy

The treatment outcomes of patients with high‐risk localized prostate cancer (PC) after carbon‐ion radiotherapy (CIRT) combined with long‐term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC‐specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed‐dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high‐risk or very‐high‐risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow‐up time was 88.4 months, and the 5‐/10‐year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9–10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10‐year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10‐year follow‐up (10‐year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high‐risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high‐risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high‐risk PC patients treated with CIRT.     

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.     

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.     

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.     

Predictors of clinical metastasis in prostate cancer patients receiving androgen deprivation therapy

BACKGROUND:

Virtually all patients with prostate cancer who receive androgen deprivation therapy (ADT) will ultimately develop evidence of resistance to treatment. The prognosis for patients who develop metastatic castrate‐resistant disease is reported to be poor, with overall survival historically estimated to be 24 to 36 months. The goal of the current study was to identify predictors of clinical disease progression in patients with prostate cancer who were receiving ADT.

METHODS:

Of the 13,740 men with biopsy–proven prostate cancer who were enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database from 1995 to 2007, 4003 men treated with ADT after diagnosis without evidence of metastases at treatment initiation were identified. The primary endpoint was the development of bone metastasis. Clinical and pathologic characteristics were compared between patients who developed metastasis and those who did not using chi‐square tests in a Cox proportional hazards regression model.

RESULTS:

The mean age of the men in the cohort was 70 years (range, 39‐94 years). One hundred ninety‐one men (4.8%) progressed to metastatic disease at a median of 18 months from the initiation of ADT (range, 1‐139 months). On multivariate analyses, risk category (hazards ratio [HR], 2.58; P < .0001), percent of biopsies positive >33% (HR, 3.36; P = .003), age ≤65 years at diagnosis (HR, 2.11; P = .001, and prostate–specific antigen velocity on ADT (HR, 1.04; P < .001) were found to be significantly associated with the development of metastatic disease after ADT.

CONCLUSIONS:

Younger men with high–risk disease appear to have worse prognosis than older men with similar disease. This, along with the other prognostic variables established in the current study, may help identify candidates for clinical trials evaluating secondary treatments for patients with castrate‐resistant disease. Cancer 2009. © 2009 American Cancer Society.     

Stereotactic radiosurgery of World Health Organization grade II and III intracranial meningiomas: treatment results on the basis of a 22-year experience

BACKGROUND:

A study was undertaken to define the variables associated with tumor control and survival after single‐session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas.

METHODS:

Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm³; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow‐up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22).

RESULTS:

Tumor grade correlated with disease‐specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression‐free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm³ were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation‐related complications at a median of 6 months after radiosurgery.

CONCLUSIONS:

Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas. Cancer 2012;. © 2011 American Cancer Society.     

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

BACKGROUND:

A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival. We report on the quality of life (QOL) outcomes for this trial.

METHODS:

From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were randomly assigned to cryoablation or EBRT (median dose 68 Gy). All patients received neoadjuvant antiandrogen therapy. Patients completed the EORTC QLQ C30 and the Prostate Cancer Index (PCI) before treatment and at 1.5, 3, 6, 12, 18, 24, and 36 months post‐treatment.

RESULTS:

Regardless of treatment arm, participants reported high levels of QOL with few exceptions. cryoablation was associated with more acute urinary dysfunction (mean PCI urinary function cryoablation = 69.4; mean EBRT = 90.7; P < .001), which resolved over time. No late arising QOL issues were observed. Both EBRT and cryoablation participants reported decreases in sexual function at 3 months with the cryoablation patients reporting poorer functioning (mean cryoablation = 7.2: mean EBRT = 32.9; P < .001). Mean sexual function score was 15 points lower at 3 years for the cryoablation group and 13% more of the cryoablation men said that sexuality was a moderate or big problem.

CONCLUSIONS:

In this randomized trial, no long‐term QOL advantage for either treatment was apparent with the exception of poorer sexual function reported by those treated with cryoablation. Men who wish to increase their odds of retaining sexual function might be counseled to choose EBRT over cryoablation. Cancer 2009. © 2009 American Cancer Society.     

Comparison of intensity‐modulated radiotherapy and 3‐dimensional conformal radiotherapy as adjuvant therapy for gastric cancer

BACKGROUND:

The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity‐modulated radiotherapy (IMRT) versus 3‐dimensional conformal radiotherapy (3D CRT).

METHODS:

Fifty‐seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n = 31), 5‐fluorouracil (5‐FU) (n = 25), or none (n = 1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups.

RESULTS:

The 2‐year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P = .5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade ≥2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P = .02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P = .05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P = .17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P = .19). The median liver V30 was 16.1% and 28%, respectively (P < .001).

CONCLUSIONS:

Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function. Cancer 2010. © 2010 American Cancer Society.