综合性运动训练预防前列腺癌患者雄激素剥夺疗法的副作用

目的:探讨在雄激素剥夺疗法（ADT）开始的同时进行综合运动干预能否降低前列腺癌患者ADT的副作用。方法:70例开始使用醋酸亮丙瑞林(lucrin)进行治疗的前列腺癌患者随机分为运动组和对照组,每组35例。运动组开展包括抗阻训练、有氧运动和冲击加载运动,每周3次,连续3个月。对照组不进行运动干预。在开始干预前（基线期）和干预后(3个月)评估患者身体组成成分、骨密度、身体机能、血生化指标和基于SF-36、QLQ-PR25、FACIT-Fatigue、BSI-18等量表评价的健康相关生活质量。采用协方差分析(ANCOVA)比较调整了组间差异后干预前后各变量的变化情况。结果:运动干预3个月后,与基线期相比较,试验组的四肢瘦体组织［ 95%CI:0.4(0.1~0.7) kg,P=0.029］和全身瘦体组织［ 95%CI:0.7(0.1~1.6) kg,P=0.054］在调整了组间差异后均有显著增加。而运动组全身脂肪量及其比例、躯干脂肪量在调整组间差异后均有降低 (P＜0.01或P＜0.001)。与对照组比较,试验组患者的股骨颈变化值［ 95%CI:0.012(0.005~0.024) kg,P=0.032］、胫骨骨密度变化值［ 95%CI:20.0(12.5~29.5) kg,P=0.019］差异有统计学意义。与对照组比较,试验组在心肺功能(VO2 peak)、上肢肌肉和下肢肌肉的最大力量（胸部推举、腿部推蹬和坐姿划船）、肢体功能（椅子起立试验）方面均有显著的改善（P＜0.05或P＜0.01）。两组间在行走能力、平衡能力和平衡信心方面得分差异无统计学意义（P＞0.05）。组间总胆固醇/HDL比值差异有统计学意义（P=0.027）。干预后患者性功能和疲劳感也得到了改善。结论:当开始ADT的同时启动包括有氧运动、抗阻运动和冲击加载运动的综合性运动计划,可以改善患者身体成分、身体功能、总胆固醇/HDL比例、性功能、疲劳严重程度。本研究扩展了运动干预对于改善ADT治疗前列腺癌的副作用的有效性的证据。     

Management of complications of prostate cancer treatment.

Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the United States. Treatment of men with prostate cancer commonly involves surgical, radiation, or hormone therapy. Most men with prostate cancer live for many years after diagnosis and may never suffer morbidity or mortality attributable to prostate cancer. The short-term and long-term adverse consequences of therapy are, therefore, of great importance. Adverse effects of radical prostatectomy include immediate postoperative complications and long-term urinary and sexual complications. External beam or interstitial radiation therapy in men with localized prostate cancer may lead to urinary, gastrointestinal, and sexual complications. Improvements in surgical and radiation techniques have reduced the incidence of many of these complications. Hormone treatment typically consists of androgen deprivation therapy, and consequences of such therapy may include vasomotor flushing, anemia, and bone density loss. Numerous clinical trials have studied the role of bone antiresorptive therapy for prevention of bone density loss and fractures. Other long-term consequences of androgen deprivation therapy may include adverse body composition changes and increased risk of insulin resistance, diabetes, and cardiovascular disease. Ongoing and planned clinical trials will continue to address strategies to prevent treatment-related side effects and improve quality of life for men with prostate cancer.     

Intermittent androgen deprivation

Intermittent androgen deprivation is a controversial approach to management of prostate cancer. Preclinical models have demonstrated delay in time to prostatespecific antigen (PSA) progression in athymic mice bearing LNCaP tumors and a delay in time to androgen independence in androgen-dependent Shionogi carcinoma tumors in castrated animals exposed to intermittent androgen. Phase II clinical trials have demonstrated improved sexual function and quality of life in men discontinuing androgen deprivation. The average percentage of time spent off androgen deprivation ranges from 37% to 58%. Most men respond to retreatment with hormonal therapy. Current ongoing phase III clinical trials of intermittent versus continuous androgen deprivation in men with metastatic disease or recurrent disease after localized therapy will assess the comparative impact on quality of life and survival. Final analyses of these critical trials will define the ultimate role of this approach in prostate cancer. In the interim, intermittent androgen deprivation should be considered an experimental approach.     

Osteoporosis and other adverse body composition changes during androgen deprivation therapy for prostate cancer

Osteoporosis and other body composition changes are important complications of androgen deprivation therapy (ADT) for prostate cancer. Bilateral orchiectomy and gonadotropin-releasing hormone agonist treatment decrease bone mineral density and increase fracture risk. Other factors including diet and lifestyle may contribute to bone loss in men with prostate cancer. Estrogens play an important role in male bone metabolism. Androgen deprivation therapy with estrogens probably causes less bone loss than bilateral orchiectomy or gonadotropin-releasing hormone agonist treatment. Bicalutamide monotherapy increases serum estrogen levels and may also spare bone. Lifestyle modification including smoking cessation, moderation of alcohol use, and regular weight bearing exercise are recommended to decrease treatment-related bone loss. Supplemental calcium and vitamin D are also recommended. Pamidronate (Aredia®), an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective but have not been studied in hypogonadal men. Androgen deprivation therapy increases fat mass and decreases muscle mass. These body composition changes may contribute to treatment-related decreases in physical capacity and quality of life.     

Preventing bone complications in advanced prostate cancer

The diagnosis and treatment of prostate cancer have steadily been improving since the late 1980s. However, clinicians still confront a large group of men developing disease metastatic to bone. Adequate control of bone complications plays a fundamental role in achieving control of symptoms and quality of life in this group. Androgen deprivation therapy, the standard treatment for advanced prostate cancer, increases the risk of various complications, including bone disease. This review addresses the prevention of bone complications related not only to prostate cancer metastases but also to impaired bone integrity caused by androgen deprivation therapy.     

Education predicts quality of life among men with prostate cancer cared for in the Department of Veterans Affairs: a longitudinal quality of life analysis from CaPSURE

BACKGROUND: Previous findings have suggested that patient educational attainment is related to cancer stage at presentation and treatment for localized prostate cancer, but there is little information on education and quality of life outcomes. Patient education level and quality of life were examined among men diagnosed with prostate cancer and cared for within an equal-access health care system, the Department of Veterans Affairs Veterans Health Administration (VA). METHODS: Participants were 248 men with prostate cancer cared for in the VA and enrolled in CaPSURE. Repeated-measures analysis of variance was used to examine quality of life over time according to education level, controlling for age, ethnicity, income, site of clinical care, and year of diagnosis. RESULTS: Patients with lower levels of education tended to be younger, nonwhite, and have lower incomes. Controlling for age, ethnicity, income, year of diagnosis, and site, men with less formal education, compared with those with more, had worse functioning in the physical (P=.0248), role physical (P=.0048), role emotional (P=.0089), vitality (P=.0034), mental health (P=.0054), social function (P=.0056), and general health (P=.0002) domains and worse urinary (P=.003) and sexual (P=.0467) side effects. CONCLUSIONS: Men with less education experienced worse health-related quality of life across a wide range of domains and greater urinary and sexual symptoms than their peers who had more education. Clinicians should be aware that, even within an equal access to health care system, men with less education are vulnerable, having greater difficulty functioning in their daily lives after their prostate cancer treatment.     

Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer.

PURPOSE: To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy. PATIENTS AND METHODS: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity. RESULTS: At 2 years, 33% of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes. CONCLUSION: Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.     

Complications of androgen-deprivation therapy for prostate cancer

With the increasing indications for the use of androgen-deprivation therapy in the treatment of men with prostate cancer, side effects of the therapy deserve greater attention. Side effects such as hot flashes, decreased libido, decreased sexual function, and fatigue primarily affect the patients quality of life. Other side effects such as osteoporosis and changes in lipid profiles may also affect the patients overall health. Treatments such as estrogen, megestrol acetate, antidepressants, and bisphosphonates are useful in the management of many of the deleterious side effects of androgen deprivation. In addition, alternative management strategies such as intermittent androgen ablation and antiandrogen monotherapy may be useful in minimizing side effects caused by androgen ablation. Patients and physicians should be well aware of the potential side effects of androgen-deprivation therapy as well as the preventive and treatment strategies for these side effects in order to improve patients quality of life and health.     

A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma

BACKGROUND: Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma. METHODS: Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy. RESULTS: There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003). CONCLUSIONS: Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.     

A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer

Background  

Androgen deprivation therapy (ADT) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture, reduced lean mass and muscle strength, mood disturbance and increased fat mass compromising physical functioning, independence, and quality of life. The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects, and cardiovascular and diabetes risk factors in men receiving androgen deprivation for their prostate cancer. Specifically, we aim to investigate the effects of a 12-month exercise program designed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints: 1) bone mineral density; 2) cardiorespiratory function and maximal oxygen capacity; 3) body composition (lean mass and fat mass); 4) blood pressure and cardiovascular function; 5) lipids and glycemic control; and 6) quality of life and psychological distress.     

Intermittent androgen deprivation therapy for prostate cancer

Androgen deprivation therapy for prostate cancer is associated with several complications, including loss of libido, hot flashes, night sweats, psychological stress, osteoporosis, anemia, fatigue, loss of muscle mass, glucose intolerance, and changes in lipid profile. The natural history of prostate cancer while on such therapy is the attainment of an incurable androgen-independent state. Early diagnosis by prostate-specific antigen screening, longer life expectancies, and a penchant for immediate therapy pose a problem where clinicians have to balance the potential benefits of early hormonal therapy with the risks of development of these metabolic and psychological complications. Intermittent androgen deprivation offers clinicians a prospect to improve quality of life in patients with prostate cancer by harmonizing the benefits of androgen ablation with a reduction in treatment-related side effects and expenditure. In this review we discuss the challenges and opportunities of this mode of therapy and shed light on some of the underlying molecular mechanisms.     

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

Background  

A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.     

Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study.

PURPOSE: To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer. PATIENTS AND METHODS: Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade. RESULTS: More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also were less likely to consider themselves free of prostate cancer after treatment. CONCLUSION: Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions.     

Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer.

PURPOSE: Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor-regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA. EXPERIMENTAL DESIGNS: Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry. Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received. RESULTS: Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P=0.30). Dihydrotestosterone levels decreased 91% in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P < 0.0001) although dihydrotestosterone levels in most specimens of recurrent prostate cancer were sufficient for androgen receptor activation. Testosterone or dihydrotestosterone levels were not related to metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P > 0.2). CONCLUSIONS: Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer.     

Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.

PURPOSE: Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer. PATIENTS AND METHODS: One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks. RESULTS: Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy. CONCLUSION: Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.     

The language of prostate cancer treatments and implications for informed decision making by patients

ROT I., OGAH I. & WASSERSUG R.J. (2012) European Journal of Cancer Care The language of prostate cancer treatments and implications for informed decision making by patients Previous research has shown that cancer patients lack knowledge about treatments particularly for reproductive system cancers. Focusing on prostate cancer, we explored how the language used to describe treatments and their side effects is understood by both men and women. Since the language around prostate cancer is often euphemised to reduce distress and stigma, our aim was to elucidate how language (e.g. hormone therapy vs. androgen deprivation therapy) affects both patients' and partners' attitudes towards treatment decision making. We surveyed 690 male and female cancer patients and non‐patients through an online questionnaire. A large proportion of participants did not understand the terminology used to describe prostate cancer treatments. Most did not know that the terms ‘chemical castration’, ‘hormonal therapy’ and ‘androgen deprivation’ are synonymous. Male respondents stated that they would more readily agree to hormonal therapy than to castration to treat prostate cancer and felt significantly more strongly than women about how androgen deprivation therapy, described in various terms, affected masculinity. Men and women differed substantially in their opinion about the impact of androgen deprivation. For patients and partners to make informed decisions and cope effectively with treatment side effects, it is important that healthcare practitioners provide accurate information using language that is unambiguous.     

A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy

For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone health in men with prostate cancer receiving adt and the current evidence regarding bone-health monitoring and management in reference to Canadian provincial guidelines. Based on this narrative review, we provide general bone-health management recommendations for men with prostate cancer receiving adt.     

Effect of Exercise Adjunct to Radiation and Androgen Deprivation Therapy on Patient-Reported Treatment Toxicity in Men With Prostate Cancer: A Secondary Analysis of 2 Randomized Controlled Trials

PurposePhysical inactivity, in addition to clinical factors, has been associated with higher levels of late pelvic symptoms in patients with prostate cancer (PCa) after radiation therapy. The aim of this study was to investigate the effect of a structured multicomponent exercise program comprised of aerobic and resistance training as well as impact loading on the prevalence and severity of symptoms commonly resulting from androgen deprivation therapy (ADT) and pelvic radiation therapy.Methods and MaterialsWe performed a secondary analysis of pooled data from 2 randomized controlled trials that investigated the role of exercise on treatment-related side effects in patients with PCa receiving ADT. Patients were included in the analysis if they had undergone radiation therapy during the intervention in addition to ADT. Patient-reported quality of life and functional and symptom scales were assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and PR25 before and after 6 months of exercise or usual care (UC).ResultsOne-hundred and fifteen patients with PCa receiving ADT, aged 47 to 84 years, who also underwent radiation therapy were included in the analysis (exercise, n = 72; UC, n = 43). There was a significant reduction in physical functioning (P = .019) and increased fatigue (P = .007) in the control group, with no change observed in the exercise group. Similarly, there was a trend toward reduced sexual activity in the control group (P = .064), with a mean adjusted change of -7.1 points. Furthermore, the prevalence of clinically important pain at 6 months was lower in the exercise group compared with UC (18.1 vs 37.2%, P = .022). No between-group differences were found for urinary (P = .473) or hormonal treatment-related symptoms (P = .552).ConclusionsExercise during concomitant hormone and radiation treatment for men with PCa may mitigate some adverse changes in patient-reported fatigue, physical functioning, and possibly sexual activity. The promotion and provision of exercise to counter a range of treatment-related adverse effects in patients with PCa undergoing radiation therapy and ADT should be actively encouraged.