Effect of androgen deprivation therapy on quality of life in Japanese men with prostate cancer

OBJECTIVE: We evaluated health-related quality of life (HRQOL) in Japanese men receiving androgen deprivation therapy (ADT) for prostate cancer. METHODS: Fifty-six men were enrolled in this study. HRQOL was prospectively measured before ADT, and at 3, 6 and 12 months after treatment began, using a general (36-item Short-Form Health Survey) and disease-specific (the University of California, Los Angeles Prostate Cancer Index) HRQOL questionnaire. RESULTS: In the general HRQOL questionnaire, patients with stage B (n = 22) or C (n = 17) disease showed a decline in vitality at 6 and 12 months (P < 0.05 for both). Stage D patients (n = 17) had improvements in bodily pain at 3 and 12 months (P < 0.05 for both), vitality at 12 months (P < 0.05), role-emotional at 6 months (P < 0.05), and mental health at 3 months (P < 0.05). When clinical stages were not considered, there were no significant changes in the 36-item Short-Form Health Survey. As for the disease-specific HRQOL, urinary function improved after ADT at 6 and 12 months (P < 0.05 for both), and urinary bother decreased at 3 (P < 0.05), 6 (P < 0.005) and 12 months (P < 0.05). Sexual function decreased at 3 (P < 0.05), 6 (P < 0.005) and 12 months (P < 0.005) but sexual bother improved at 6 and 12 months (P < 0.05 for both). If patients were stratified by clinical stages, similar findings were observed. CONCLUSIONS: General HRQOL was mostly unaffected by ADT in Japanese men. Disease-specific questions indicated an increase in urinary function. Although deterioration of sexual function was marked, most patients did not report sexual bother. Our results shed new light on the impact of ADT on HRQOL and could provide useful information about patient-centered outcome evaluations.     

Germline CAG repeat length of the androgen receptor and time to progression in patients with prostate cancer treated with androgen deprivation therapy

Study Type – Prognosis (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Germline CAG repeat polymorphisms in the androgen receptor (AR‐CAG) have been shown to influence the activity of the androgen receptor, but there has been conflicting data from small retrospective studies evaluating the effect of CAG repeat polymorphisms on response to ADT. This is the largest published study to date investigating the association of germline AR‐CAG repeat lengths and efficacy of ADT in prostate cancer. Germline AR‐CAG repeat lengths do not predict response to ADT.

OBJECTIVES

? Germline CAG repeat polymorphisms in the androgen receptor (AR‐CAG) have been shown to influence the activity of the AR. ? The purpose of the present study was to determine if AR‐CAG repeat length correlates with time to progression on androgen deprivation therapy (ADT).

PATIENTS AND METHODS

? Germline AR‐CAG repeat lengths were determined in a cohort of 480 patients with recurrent or metastatic prostate cancer treated at a single tertiary care institution and correlated to time to progression (TTP) and overall survival.

RESULTS

? There was no significant correlation between differences in the AR‐CAG repeat lengths and TTP or overall survival in patients with prostate cancer receiving ADT. ? AR‐CAG repeat lengths did not significantly correlate with age, prostate‐specific antigen (PSA), Gleason score or clinical stage at diagnosis. ? In patients with metastatic disease, longer AR‐CAG repeat lengths (>23 vs ≤23) were associated with a longer TTP on ADT, but this finding was of borderline significance (median TTP 18.3 vs 15.5 months, P= 0.09; adjusted HR = 0.76, 95% confidence interval = 0.54–1.09).

CONCLUSIONS

? This is the largest published study to date investigating the association of germline AR‐CAG repeat lengths and efficacy of ADT in prostate cancer. ? Germline AR‐CAG repeat lengths do not predict response to ADT.     

前列腺癌患者的生活质量与自我形象研究

目的 了解前列腺癌患者的生活质量、接受雄激素去除治疗与否生活质量的差异性及自我形象与生活质量的相关性,为提高患者生活质量干预提供依据.方法 对155例前列腺癌患者采用自我形象量表、生活质量量表及前列腺癌特异性补充量表测量其生活质量和自我形象的认知,分析两者的相关性.结果 患者自我形象得分6.32±4.82,生活质量总分...     

Quality of life issues in men undergoing androgen deprivation therapy: a review

Androgen deprivation therapy (ADT) has been an essential treatment option for treating prostate cancer (PCa). The role for hormonal treatment initially was restricted to men with metastatic and inoperable, locally advanced disease. Now it has been extended to neoadjuvant or adjuvant therapy for surgery and radiotherapy, for biochemical relapse after surgery or radiation, and even as primary therapy for non-metastatic disease. Fifty percent of PCa patients treated will receive ADT at some point. There is growing concern about the adverse effects and costs associated with more widespread ADT use. The adverse effects on quality of life (QoL), including physical, social and psychological well-being when men are androgen-deprived, may be considerable. This review examines the QoL issues in the following areas: body feminisation, sexual changes, relationship changes, cognitive and affective symptoms, fatigue, sleep disturbance, depression and physical effects. Further suggestions for therapeutic approaches to reduce these alterations are suggested.     

Effect of androgen deprivation therapy on bone mineral density in prostate cancer patients

Aim: To evaluate the effect of androgen deprivation therapy (ADT) on bone mineral density (BMD) in prostate cancer patients. Methods: Forty-nine prostate cancer patients with their BMD determined were divided into two groups: the non-treated group included 21 patients before the commencement of ADT and the treated group, 28 patients, who had received ADT for more than 1 year. BMD was measured by dual energy X-ray absorptiometry (DEXA) in the lumbar spine (L2-4) and femoral neck. Results: Thirteen (62 %) non-treated and 23 (82 %) treated patients fulfilled the BMD criteria for osteopenia or osteoporosis. Z scores for age-matched control in lumbar spine and femoral neck were -0.9 ± 0.7 and -0.6 ± 0.5, respectively, in the treated group, and -1.8 ± 1.1 and-1.6 ± 1.0 , respectively, in the non-treated group, the differences between the two groups were highly significant (P<0.01). Conclusion: Prostate cancer patients who received ADT for more than 1 year had a significantly lower BMD in the lumbar spine a     

Metabolic changes in patients with prostate cancer during androgen deprivation therapy

Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new‐generation androgen‐receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events.     

Use of androgen deprivation therapy in prostate cancer: indications and prevalence

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer. This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.     

Efficacy and safety of keishibukuryogan,a traditional Japanese Kampo medicine,for hot flashes in prostate cancer patients receiving androgen deprivation therapy

BackgroundThe efficacy and safety of keishibukuryogan, a traditional Japanese medicine, were investigated for the treatment of hot flashes in prostate cancer (PC) patients receiving androgen deprivation therapy.MethodsThirty patients were enrolled and orally administered 2.5 g keishibukuryogan three times daily for 12 weeks. The frequency, strength, and duration of hot flashes were self-evaluated by the patients in a diary every 4 weeks. All patients also completed a questionnaire to determine their aging male symptoms (AMS) scale score and underwent blood biochemical testing.ResultsTwenty-five patients completed the 12-week treatment. Hot flash strength significantly improved 4, 8, and 12 weeks after treatment. Their frequency was significantly reduced at the 8-week visit, and duration was significantly shorter after the 8-week visit. In addition, the score of the AMS somatic subscale was improved at the 8- and 12-week visits. Among the somatic items, questions 3 (excessive sweating) and 5 (increased need for sleep) were significantly improved. Obesity, radiation, and a longer duration of PC were predictive factors for treatment response. Prostate specific antigen and total testosterone levels were unchanged, and no patients had severe adverse effects.ConclusionsKeishibukuryogan was an effective and safe treatment for hot flashes in PC patients.     

Increased risk of a herpes zoster attack in patients receiving androgen deprivation therapy for prostate cancer

This study aimed to examine the association of herpes zoster (HZ) with androgen deprivation therapy (ADT) use among patients with prostate cancer (PC), using a population‐based data set. The study sample for this study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We selected 877 patients with PC who had received ADT as the study group, while 849 patients with PC who had not received ADT served as the comparison group. Each study patient was individually tracked for a 3‐year period to discriminate those who subsequently received a diagnosis of HZ. Of the total 1,726 sampled patients, the incidence rate of HZ per 100 person‐years was 1.80 (95% CI: 1.41–2.25) during the 3‐year follow‐up period. In particular, incidence rates of HZ per 100 person‐years were 2.36 (95% CI: 1.75–3.13) and 1.24 (95% CI: 0.81–1.81), respectively, for patients with PC who had and those who had not received ADT. Furthermore, Cox proportional hazard regressions showed that the adjusted hazard ratio for an HZ attack during the 3‐year follow‐up period for patients with PC who had received ADT was 1.88 (95% CI: 1.13–3.11) than those who had not received ADT. We concluded that patients with PC who had received ADT had an increased risk of HZ.     

Use of androgen deprivation therapy for metastatic prostate cancer in older men

OBJECTIVE

To assess factors associated with early or delayed androgen deprivation therapy (ADT) among men diagnosed with metastatic prostate cancer, and to assess the relationship between ADT and overall survival, as there is uncertainty about the ideal timing for initiating ADT in men with metastatic prostate cancer.

PATIENTS AND METHODS

We studied a population‐based cohort of American men aged ≥66 years diagnosed with metastatic prostate cancer during 1992–2002 and followed to 2003. We assessed the receipt of ADT early (≤4 months from diagnosis), delayed (>4 months), or not at all, using multinomial logistic regression to identify factors associated with treatment, and Cox proportional‐hazard models to assess whether treatment was associated with survival.

RESULTS

Overall, 69.5% of men received early ADT and 7.3% delayed. Adjusted rates of early ADT were lower for black than white men (58.3% vs 71.0%), and of delayed ADT were higher for black than white men (12.7% vs 6.2%). Receipt of ADT was associated with improved survival (adjusted hazard ratio 0.69, 95% confidence interval 0.66–0.73). The benefit of early treatment did not differ from delayed treatment (P = 0.58).

CONCLUSIONS

A large minority of men with metastatic prostate cancer, particularly black men, receive delayed or no ADT. Early or delayed ADT was associated with similarly prolonged survival. After controlling for patient and tumour characteristics, survival did not differ by race, and receipt of ADT did not contribute to racial differences in survival.     

Targeted-cryosurgical ablation of the prostate with androgen deprivation therapy： quality of life in high-risk prostate cancer patients

Aim:To present preliminary results on health-related quality of life(QoL),prostate-associated symptoms and thera-peutic effects of targeted-cryosurgical ablation of the prostate(TCSAP)with androgen deprivation therapy(ADT)inhigh-risk prostate cancer(PCa)patients.Methods:Thirty-four men with high-risk PCa features underwent TCSAP,and ADT was added to improve the treatment outcomes.High-risk parameters were defined as either prostate-specific antigen(PSA)≥10ng/mL,or Gleason score≥8,or both.The Genito-Urinary Group of the European Orga-nization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30(EORTC QLQ-C30)withprostate-cancer-specific module(QLQ-PR25)was used for evaluating morbidities and PSA levels were recordedevery 3 months.PSA failure was defined as the inability to reach a nadir of 0.4 ng/mL or less.Results:Although itwas not statistically significant,the global health status scores increased after TCSAP with ADT.The scores for fivefunctional scales also became higher after treatment.The most prominent symptom after treatment was sexualdysfunction,followed by treatment-related and irritative voiding symptoms.Conclusion:TCSAP with ADT appearsto be minimally invasive with high QoL except for sexual dysfunction.Long-term follow-up of PSA data and survivalis necessary before any conclusions can be made on the efficacy of this promising new therapeutic modality in thetreatment of PCa.(Asian J Androl 2006 Sep;8:629-636)     

Impact of adjuvant androgen deprivation therapy after radical prostatectomy on the survival of patients with pathological T3b prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Adjuvant hormonal therapy is known to improve cancer specific survival in prostate cancer patients with lymph node positive disease. This study suggests that surgically treated prostate cancer patients with seminal vesical invasion (pT3b) may have improved cancer specific survival if treated with adjuvant androgen deprivation therapy, similar to lymph node positive patients.

OBJECTIVE

To determine the impact of adjuvant androgen deprivation therapy (ADT) on survival in patients with seminal vesicle invasion (pT3b) at radical prostatectomy.

PATIENTS AND METHODS

We reviewed 12 115 patients who underwent radical prostatectomy between 1987 and 2002 to identify patients with pT3bN0 prostate cancer who received adjuvant ADT (n= 191). These patients were matched by clinical and pathological variables to a group of patients with pT3b prostate cancer who did not receive adjuvant ADT. Median postoperative follow‐up was 10 years. Clinical endpoints included biochemical progression‐free survival (BPFS), local recurrence‐free survival (LRFS), systemic progression‐free survival (SPFS), cancer‐specific survival (CSS) and overall survival.

RESULTS

Patients who underwent adjuvant ADT experienced improved 10‐year BPFS (60% vs 16%, P < 0.001), LRFS (87% vs 76%, P= 0.002), SPFS (91% vs 78%, P= 0.004) and CSS (94% vs 87%, P= 0.037). Overall survival was not significantly different between groups (75% vs 69%, P= 0.12). Both luteinizing hormone‐releasing hormone agonists (hazard ratio, 0.26; 95% CI, 0.15–0.46; P < 0.001) and bilateral orchiectomy (hazard ratio, 0.13; 95% CI, 0.06–0.31; P < 0.001) improved BPFS. When stratified by type of ADT (hormonal therapy vs orchiectomy), there was no difference in survival outcomes.

CONCLUSIONS

Adjuvant ADT improves local, and systemic control after radical prostatectomy for pT3b prostate cancer. There is no difference in survival between patients receiving medical hormonal therapy vs patients undergoing orchiectomy. Given the lack of improvement in overall survival, continued investigation is needed to identify the cohort of pT3b patients at highest risk for cancer progression and therefore most likely to benefit from a multimodal treatment approach.     

Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2) and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites) involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene combinations and personalize the management of prostate cancer.     

Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

Prostate cancer (PCa) is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy (ADT) is used in the management of locally advanced (improves survival) and metastatic (improves pain and quality of life) PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.