Pretreatment prostate-specific antigen velocity is associated with development of distant metastases and prostate cancer mortality in men treated with radiotherapy and androgen-deprivation therapy

BACKGROUND: In men with prostate cancer, pretreatment prostate-specific antigen (PSA) velocity (PSAV) has been demonstrated as a predictor of biochemical and survival outcomes in patients undergoing radical prostatectomy (RP). The utility of pretreatment PSAV in predicting outcomes after radiotherapy (RT), with or without androgen-deprivation therapy (ADT), is less certain. This study was undertaken to determine whether pretreatment PSAV is associated with biochemical disease-free survival, patterns of recurrence, and survival outcomes in men treated with radiation therapy and ADT. METHODS: Two hundred seventy-seven patients with intermediate- and high-risk prostate cancer treated with RT and ADT formed the study cohort. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate whether PSAV was associated with disease outcomes. RESULTS: The median age of diagnosis was 70 years, and the median follow-up was 6.8 years. Men with a PSAV in the highest quartile tended to have higher risk disease at presentation (P = .028). After adjustment for known prognostic factors and duration of ADT, men who had a PSAV in the highest quartile had an increased risk of distant metastasis (hazard ratio [HR], 4.0; 95% confidence interval [95% CI], 1.61-9.9 [P = .003]) and prostate cancer-specific mortality (HR, 2.75; 95% CI, 1.27-5.95 [P = .01]) compared with men who had a lower PSAV, but had no increase in the risk of local recurrence (P = .76). CONCLUSIONS: A high pretreatment PSAV was associated with distant metastasis and prostate cancer-specific mortality but not with local recurrence. A high pretreatment PSAV may signify the presence of occult metastatic disease. Randomized trials are needed to determine whether more aggressive intervention is required in men who present with high pretreatment PSAV.     

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.     

以骨转移癌为首发表现的前列腺癌诊治分析

目的:对以骨转移癌为首发表现的前列腺癌患者进行分析,提高对晚期前列腺癌的认识。方法:对32例以骨转移癌为首发表现的前列腺癌患者症状与体征、实验室检查、影像学检查、病理学检查结果等资料进行回顾分析。结果:32例患者表现为骨痛25例(78.13%),凝血功能障碍、贫血10例(31.25%),发热2例(6.25%),伴有泌尿系统症状8例(25%),血清前列腺特异性抗原(PSA):PSA>50ng/ml者15例,PSA>100ng/ml者8例,碱性磷酸酶升高(超过150U/L)13例(72%)。进一步行骨核素扫描见多发、散在、无规律的放射性增高或浓聚灶,骨转移瘤见于腰骶椎体、髋骨占30例（93.75%）,其次为肋骨和胸骨,伴一处或以上的脏器转移占6例(18.75%)。追问病史发现前列腺癌诊断线索8例。经前列腺穿刺活组织检查确诊前列腺癌22例,临床诊断10例。结论:对于临床上出现不明原因骨痛、凝血功能障碍、贫血、发热等症状的老年男性患者,应考虑到前列腺癌伴骨转移可能,应常规查血PSA,据情行骨扫描及骨髓活检等检查。     

骨转移前列腺癌的临床诊治研究报道

Objective:To summarize the experience of diagnosis and treatment outcomes for bone metastatic prostate cancer.Methods:A retrospective study with a total of 128 prostate cancer(Pca) was performed from 2000 to 2005,in our institute.We analyzed the clinical features and outcomes of patients with bone metastases and the data and follow-up of 63 bone metastases was collected by one registrar.Cochran Armitage trend test was used for statistic analysis and a P-value of < 0.05 was taken as statistically significant.Results:The mean age was 73(range 55 to 87) years.The PSA level was from 0.083 ng/mL to 6462 ng/mL.Bone metastases morbidity had good relationship with PSA level.With the mean follow up of 30(range 6 to 72) months for 52/63(82.5%) patients,15(28.8%) died from Pca with a mean survival of 21 months and 1 patient with PSA less than 4 ng/mL at the time died from cerebrovascular suddenness 6 months post-treatment.Conclusion:The early effect of endocrine treatment for bone metastases is obvious,and palliative prostatectomy is satisfactory and able to improve the quality of life rapidly for patients with obstructive symptoms.     

Tackling non-metastatic castration-resistant prostate cancer: special considerations in treatment

Introduction: Prostate cancer (PCa) is currently the second most common cancer affecting men worldwide. Metastatic castration-resistant prostate cancer (mCRPC) is the incurable form of PCa, carrying the poorest prognosis, and can develop from non-metastatic CRPC (M0 CRPC). CRPC is defined as progression of the disease with castrate level testosterone levels, achieved with primary androgen deprivation therapy (ADT). M0 CRPC is a highly heterogeneous disease process lacking clear standard of care therapies.

Areas covered: In this review, a broad literature search was undertaken to explore data available for therapeutic options and guidelines in the management of M0 CRPC.

Expert commentary: While there are compelling data for various therapeutics for the treatment of M0 CRPC, no clear standard of care is apparent at this time. Furthermore, technological advances in imaging may have a significant impact on this future of this disease state.     

Zoledronic acid to prevent bone loss in Chinese men receiving androgen deprivation therapy for prostate cancer

Aim: To explore the bone mineral density (BMD) preservation effect of zoledronic acid and its renal safety and tolerability in Chinese patients with prostate cancer on androgen deprivation therapy (ADT). Methods: Overall 26 prostate cancer patients with ADT were given zoledronic acid 4 mg by a 15‐min i.v. infusion every 3 months for up to 12 months. Assessment was made at baseline and at 3, 6, 9 and 12 months. Dual‐energy X‐ray absorptiometry was used to measure the BMD of the lumbar spine and the femoral neck at baseline and 12 months. Results: A total of 23 of 26 recruited patients completed the study. Seven patients had bone metastases. The overall mean increase in BMD (T‐score) of the lumbar spine and femoral head from baseline to follow up at 12 months was significant (−2.32 ± 0.98 to −2.03 ± 1.08, P = 0.02 and −1.77 ± 0.72 to −1.63 ± 0.76, P = 0.01, respectively). In subgroup analyses, significant BMD improvement was observed independent of the status of bone metastasis and the means of ADT. Zoledronic acid had no adverse effect on renal function. Adverse events related to zoledronic acid were minimal. Conclusion: Zoledronic acid administered every 3 months significantly increased BMD in prostate cancer patients receiving ADT. It had a satisfactory adverse event profile and imposed minimal risk on patients' renal function.     

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.     

PSA、ECT骨显像诊断前列腺癌骨转移的临床意义

目的:探讨前列腺特异抗原(PSA)、发射型计算机断层扫描(ECT)99Tc-MDP骨显像诊断前列腺癌骨转移的临床意义。方法:对80例(骨转移组31例,非骨转移组49例)前列腺癌病人的PSA、ECT与骨转移的关系进行回顾性分析。结果:骨转移组与非骨转移组的PSA值差异有显著性(139.36μg/Lvs37.58μg/L,P<0.01);PSA与骨转移的程度正相关,PSA<10μg/L,骨转移率为15.38%;PSA<20μg/L,骨转移率为19.35%;PSA>20μg/L,骨转移率为51.02%;PSA>100μg/L,骨转移率为78.95%。结论:ECT骨显像对前列腺癌骨转移有较高的敏感性,对未经治疗的前列腺癌病人,PSA<10μg/L,前列腺癌骨转移的可能性极小;PSA>100μg/L者,骨转移的可能性极大。PSA>20μg/L,建议行ECT骨扫描。     

PSA、ECT骨显像诊断前列腺癌骨转移的临床意义

目的：探讨前列腺特异抗原（PSA）、发射型计算机断层扫描（ECT）99Tc-MDP骨显像诊断前列腺癌骨转移的临床意义。方法：对80例（骨转移组31例,非骨转移组49例）前列腺癌病人的PSA、ECT与骨转移的关系进行回顾性分析。结果：骨转移组与非骨转移组的PSA值差异有显著性（139.36μg/Lvs37.58μg/L,P〈0.01）;PSA与骨转移的程度正相关,PSA〈10μg/L,骨转移率为15.38%;PSA〈20μg/L,骨转移率为19.35%;PSA〉20μg/L,骨转移率为51.02%;PSA〉100μg/L,骨转移率为78.95%。结论：ECT骨显像对前列腺癌骨转移有较高的敏感性,对未经治疗的前列腺癌病人,PSA〈10μg/L,前列腺癌骨转移的可能性极小;PSA〉100μg/L者,骨转移的可能性极大。PSA〉20μg/L,建议行ECT骨扫描。     

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.     

晚期前列腺癌多发转移风险预测指标的探讨

目的:探讨年龄、Gleason评分、前列腺体积、治疗前血清PSA水平、雄激素阻断(ADT)后PSA水平、ECOG评分、是否有高血压、糖尿病和病理性骨折对晚期前列腺癌患者单发或多发转移的预测价值.方法:回顾性分析2005年1月至2011年8月收治的198例转移性前列腺癌患者的临床资料,应用χ2检验分析临床因素与转移部位数量的关系;多发转移的影响因素分析应用logistic回归分析;应用Kaplan-Meier 法和log-rank 检验进行生存分析.结果:晚期前列腺癌的Gleason评分8~10分(P<0.001)、ADT后PSA水平>0.2 ng/ml(P<0.001)、治疗前血清PSA水平>60 ng/ml(P=0.004)、ECOG评分≥ 2(P=0.002)和多发转移有显著的相关性;应用二维logistic回归分析研究这些变量对多发转移的影响,结果显示Gleason评分(P=0.022)、治疗前血清PSA水平(P=0.028)、ADT后PSA水平(P<0.001)和ECOG评分(P=0.001)对多发转移有显著影响;转移位置数量≥2个提示生化复发(多发:21个月 vs 单发:24个月)和生存时间(多发:36个月 vs 单发:45个月)均较短(P<0.001).结论:晚期前列腺癌的Gleason评分、治疗前血清PSA水平、ADT后PSA水平和ECOG评分与多发转移有显著正相关性;多发转移预示较短的生化复发和生存时间.     

Obesity is associated with increased risks of prostate cancer metastasis and death after initial cancer diagnosis in middle-aged men

BACKGROUND: Current research is inconclusive regarding the effect of obesity on outcomes after a prostate cancer diagnosis. The objective of this study was to examine associations between obesity and the risks of developing metastasis or prostate cancer-specific mortality in a population-based cohort of men with prostate cancer. METHODS: Seven hundred fifty-two middle-aged men with prostate cancer who were enrolled in a case-control study and remain under long-term follow-up for disease progression and mortality formed the study cohort. Body mass index (BMI) in the year before diagnosis was obtained at the time of initial interview. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of prostate cancer metastasis and mortality associated with obesity, controlling for age, race, smoking status, Gleason score, stage at diagnosis, diagnostic prostate-specific antigen level, and primary treatment. RESULTS: Obesity (BMI >or=30 kg/m(2)) was associated with a significant increase in prostate cancer mortality (HR, 2.64; 95% CI, 1.18-5.92). Among men who were diagnosed with local- or regional-stage disease, obesity also was associated with an increased risk of developing metastasis (HR, 3.61; 95% CI, 1.73-7.51). Associations generally were consistent across strata defined by Gleason score (2-6 or 7 [3 + 4] vs 7 [4 + 3] or 8-10), stage (local vs regional/distant for mortality), and primary treatment (androgen-deprivation therapy use: yes vs no). CONCLUSIONS: Obesity at the time of diagnosis was associated with increased risks of prostate cancer metastasis and death. The increased risk of prostate cancer death or metastasis associated with obesity largely was independent of key clinical prognostic factors at diagnosis.     

Evaluation of prediagnostic prostate‐specific antigen dynamics as predictors of death from prostate cancer in patients treated conservatively

Prostate‐specific antigen (PSA) dynamics have been proposed to predict outcome in men with prostate cancer. We assessed the value of PSA velocity (PSAV) and PSA doubling time (PSADT) for predicting prostate cancer‐specific mortality (PCSM) in men with clinically localized prostate cancer undergoing conservative management or early hormonal therapy. From 1990 to 1996, 2,333 patients were identified, of whom 594 had two or more PSA values before diagnosis. We examined 12 definitions for PSADT and 10 for PSAV. Because each definition required PSA measurements at particular intervals, the number of patients eligible for each definition varied from 40 to 594 and number of events from 10 to 119. Four PSAV definitions, but no PSADT, were significantly associated with PCSM after adjustment for PSA in multivariable Cox proportional hazards regression. All four could be calculated only for a proportion of events, and the enhancements in predictive accuracy associated with PSAV had very wide confidence intervals. There was no clear benefit of PSAV in men with low PSA and Gleason grade 6 or less. Although evidence that certain PSAV definitions help to predict PCSM in the cohort exist, the value of incorporating PSAV in predictive models to assist in determining eligibility for conservative management is, at best, uncertain.     

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.     

Initial treatment patterns and outcome of contemporary prostate cancer patients with bone metastases at initial presentation: data from CaPSURE

BACKGROUND: The current study utilized the CaPSURE disease registry to describe the natural history, initial treatment, and factors correlated with mortality in patients who were diagnosed with bony metastatic disease (M+) at the time of initial presentation. METHODS: Treatment patterns at the time of diagnosis were analyzed. Two Cox proportional hazards models were developed, with outcomes of all cause-specific mortality and prostate cancer-specific mortality in patients with M+ disease. Clinical and sociodemographic variables were included in a backward stepwise procedure to identify predictors of mortality. RESULTS: Of 12,005 patients diagnosed between 1990-2004, 284 (2.4%) were diagnosed with M+ disease. After a median follow-up period of 3.8 years, 107 patients (39%) died. Of those who died, 68 (64%) died of causes related to prostate cancer, whereas 39 (36%) had died of causes not related to prostate cancer. The 5-year survival of all patients was 71% and the median survival had not been reached at the time of last follow-up. Approximately 84% of patients received some form of hormonal therapy within 6 months of diagnosis, the use of which increased throughout the study period. Prostate cancer-specific mortality was found to be correlated with the presence of comorbid illness, younger age at diagnosis, and a Gleason score >7 in the primary tumor. CONCLUSIONS: Patients with M+ prostate cancer have a protracted natural history and a median survival that exceeds 5 years. Hormonal therapy is the mainstay for such patients. Comorbid illness, young age at diagnosis, and cancer grade appear to negatively affect the disease-specific survival.     

以肺转移癌为首发表现的前列腺癌长期存活1例报告并文献复习

目的:探讨转移性去势抵抗前列腺癌长期存活的特点及治疗方法。方法:对1例以肺转移为首发表现的前列腺癌长期存活病人的临床资料进行回顾性分析,并复习相关文献。结果:本例发现时即有肺转移的前列腺癌晚期病人,经过手术去势和间断的联合药物激素阻断治疗、化疗和新型抗前列腺癌药物阿比特龙等综合治疗,存活19年,且目前仍病情较平稳。结论:对于转移性前列腺癌应采取个体化的综合治疗,以期达到最佳的治疗效果。     

Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer

BACKGROUND: The use of androgen deprivation therapy (ADT) in the treatment of men with prostate cancer has risen sharply. Although cardiovascular disease is the most common reason for death among men with prostate cancer who do not die of the disease itself, data regarding the effect of ADT on cardiovascular morbidity and mortality in men with prostate cancer are limited. In the current study, the authors attempted to measure the risk for subsequent cardiovascular morbidity in men with prostate cancer who received ADT. METHODS: A cohort of newly diagnosed men in a population-based registry who were diagnosed between 1992 and 1996 were identified retrospectively. A total of 22,816 subjects were identified after exclusion criteria were applied. Using a multivariate model, the authors calculated the risk of subsequent cardiovascular morbidity in men with prostate cancer who were treated with ADT, as defined using Medicare claims. RESULTS: Newly diagnosed prostate cancer patients who received ADT for at least 1 year were found to have a 20% higher risk of serious cardiovascular morbidity compared with similar men who did not receive ADT. Subjects began incurring this higher risk within 12 months of treatment. However, Hispanic men were found to have a lowered risk for cardiovascular morbidity. CONCLUSIONS: ADT is associated with significantly increased cardiovascular morbidity in men with prostate cancer and may lower overall survival in men with low-risk disease. These data have particular relevance to decisions regarding the use of ADT in men with prostate cancer in settings in which the benefit has not been clearly established. For men with metastatic disease, focused efforts to reduce cardiac risk factors through diet, exercise, or the use of lipid-lowering agents may mitigate some of the risks of ADT.