Neoadjuvant hormonal therapy for prostate cancer

There have been expectations that neoadjuvant hormonal therapy would decrease the rate of positive surgical margins and, therefore, to improve the patient's survival rate after radical prostatectomy for clinically localized prostate cancer. A review of seven prospective randomized studies for clinically localized prostate cancer revealed a significant decrease in the positive surgical margin rate in cases of clinical T2 disease after neoadjuvant hormonal therapy with prostatectomy. However, this treatment did not alter the rate of seminal vesicle invasion or lymph node metastasis after radical prostatectomy. There was no difference in operative blood loss, operating time, complication rate or hospital stay between patients treated with neoadjuvant hormonal therapy and controls. Furthermore, there was no improvement in prostate specific antigen-free survival rate after a maximum of 4 years follow-up. Further research is required to determine the optimal duration of neoadjuvant hormonal therapy and whether this therapy increases the survival rate. Neoadjuvant hormonal therapy before radical prostatectomy is not supported by any outcome at this point and its use remains in the investigational stage.     

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.     

Recent advances in hormonal therapy for advanced prostate cancer

Hormonal treatment of advanced prostate cancer should be considered for patients who have stages C and D1 disease, a high risk of recurrence after local therapy, or prostate-specific antigen-measured recurrence after local treatment. This approach is dependent on most prostate cancer cells being androgen-dependent, but androgen-independent cells may arise after several years of hormonal therapy. Options for androgen blockade primarily include orchiectomy, luteinizing hormone-releasing agonists and antagonists, and nonsteroidal antiandrogens. There is some controversy regarding combined androgen blockade, intermittent androgen blockade, and the question of whether early androgen blockade is superior to delayed therapy. Convincing data do exist for the use of adjuvant/neoadjuvant hormonal therapy with external-beam radiation therapy. Although hormonal therapy is an important treatment modality for advanced prostate cancer, long-term treatment carries significant side effects that need to be considered.     

Role of hormonal profile in adjusting therapy for prostate cancer

Changes in testosterone, prolactin and estradiol levels were evaluated vis-a-vis outcome and different patterns of androgen suppression--continuous androgen blockade or intermittent therapy--for prostate cancer patients. There was a significant difference between pre- (3.4 +/- 0.5 mM/l) and post- (1.0 +/- 0.3 mM/l) treatment levels of testosterone in cases of tumor progression and that in patients with positive response--(9.1 +/- 0.6 mM/l) and (4.3 +/- 0.4 mM/l), respectively. Relatively low levels of testosterone involved tumor progression. Prolactin level was significantly higher in patients with multiple distant metastases--(18.6 +/- 1.2 microg/l) and isolated foci--(9.5 +/- 0.8 microg/l) while tumor progression was associated with enhancing correlation with PSA concentration. It was established that prolactin level can be used as a criterion for resumption or discontinuation of intermittent therapy. Estradiol dynamics was similar to that of prolactin. The difference between pre- (172.9 +/- 9.8 pM/l) and post- (246.5 +/- 12.8 pM/l) treatment levels of estradiol in cases of tumor progression was significantly higher than that in patients with positive response (85.0 +/- 3.8 pM/l) and (76.9 +/- 4.4 pM/l), respectively.     

The current state of hormonal therapy for prostate cancer

Androgen deprivation therapy remains a mainstay of treatment for men with prostate cancer. New uses for hormonal therapy, including use in the adjuvant and neoadjuvant setting, are being evaluated. Prevention of the side effects of therapy has led to the development of alternative schedules and therapeutics.     

晚期前列腺癌患者间歇性内分泌治疗的疗效观察

背景与目的：间歇性内分泌治疗是晚期前列腺癌患者的一种新的治疗策略,但该方法的运用仍然存在一定争议。该研究旨在探讨晚期前列腺癌患者行间歇性内分泌治疗的疗效,并对影响疗效的因素进行分析。方法：选取2009年7月—2015年5月间在我院治疗的晚期前列腺癌患者,均先进行6个月的内分泌治疗,然后评估内分泌治疗的疗效,采用随机数表法将对内分泌治疗敏感的患者分为持续治疗组和间歇治疗组,观察两组患者的疗效、患者的生活质量评分及不良反应等指标,并分析影响间歇治疗组患者预后的相关因素。结果：共收治晚期前列腺癌患者128例,经前期内分泌治疗后有96例前列腺特异性抗原(prostate-specific antigen,PSA)明显下降,其中43例患者接受间歇性内分泌治疗,53例患者接受持续性内分泌治疗。间歇组患者治疗间歇期的KPS评分为82.6±7.4,明显高于持续组患者治疗期间的KPS评分(69.8±8.7),两者之间差异有统计学意义(P<0.05)。间歇组患者治疗相关的不良反应发生率、发展成为非激素依赖性的比例均明显低于持续治疗组,差异有统计学意义(P<0.05)。间歇组5年生存率为72.1%,高于持续组的63%,但两者比较差异无统计学意义(P＞0.05)。前期内分泌治疗后的PSA水平及患者治疗前的Gleason评分是患者预后的重要影响因素。间歇组随访13~70个月,患者接受1～4个循环的治疗。随着治疗时间的延长,参与治疗的例数越来越少,两次治疗的间隔也越来越短。结论：间歇性内分泌治疗是一种有效的治疗晚期前列腺癌的方法,疗效满意,安全可靠,能有效改善患者的生活质量,且能使患者的经济负担明显减轻。     

Stereotactic body radiation therapy for prostate cancer

Stereotactic body radiation therapy (SBRT) is a promising treatment option for prostate cancer. Hypofractionation regimens, such as SBRT, may be more advantageous compared with conventional regimens because low α:β ratio of prostate cancer has high sensitivity to dose per fraction. In addition, a smaller and tighter margin with SBRT is expected to provide a low toxicity rate without reducing tumor control. The purpose of this article is to examine radiobiological, technical and clinical aspects of SBRT for prostate cancer.     

Initial decline in hemoglobin during neoadjuvant hormonal therapy predicts for early prostate specific antigen failure following radiation and hormonal therapy for patients with intermediate and high-risk prostate cancer

BACKGROUND: Declines in serum hemoglobin (Hgb) levels occur from the use of androgen suppression therapy (AST) in the treatment of prostate cancer patients. We studied whether time to prostate specific antigen (PSA) failure following external beam radiation therapy (RT) and AST could be predicted by the rate of decline in the Hgb level following the administration of neoadjuvant AST or by the Hgb level at presentation or at the start of RT. METHODS: The study cohort comprised 110 intermediate or high-risk prostate cancer patients who were managed using three-dimensional conformal RT (70 Gy) and 6 months of AST (2 months neoadjuvant, concurrent, and adjuvant). A Cox regression multivariable analysis was performed to evaluate the ability of the rate of decline of the Hgb from baseline to the start of RT, baseline PSA level, Gleason score, percent positive biopsies, and T-category to predict time to PSA failure. RESULTS: A decline in the Hgb level of 1 g/dL or more during the first month of AST was the only significant predictor of time to PSA failure (P = 0.02) on multivariable analysis. The relative risk of PSA failure (95% confidence interval) for patients with a decline in Hgb level during the first month (> or = 1 g/dL vs. < 1 g/dL) was 6.3 (2.4, 8.3) and the 3-year estimate of PSA outcome was 66% versus 82% (P = 0.04), respectively. There were no imbalances in the pretreatment prognostic factors or length of follow-up in each of these groups. CONCLUSION: A decline of 1 g/dL or more in Hgb level during the first month of neoadjuvant AST was a predictor of early PSA failure following RT and AST in intermediate and high-risk prostate cancer patients.     

Changes in body composition during neoadjuvant therapy can affect prognosis in rectal cancer patients: An exploratory study

Aim: To establish the correlation between changes in body composition after neoadjuvant chemoradiotherapy (nCRT) and postoperative outcomes, in patients with advanced low rectal cancer. Methods: Patients with clinical stage T≥3 or N+ rectal cancer who underwent nCRT and surgical resection were studied. Skeletal muscle, visceral, and subcutaneous fat cross-sectional area were measured by computed tomography before and after nCRT. Postoperative morbidity, pathologic response to nCRT, overall and disease-free survival was assessed. Results: Fifty-two patients, median age 62 (range 32-79) were studied. A skeletal muscle loss >2% significantly correlated with a shorter disease-free survival both in the overall population (P = 0.048) and in the subgroup of N0 patients (P = 0.048). A subcutaneous fat loss >5% was also associated with a shorter disease-free survival (P = 0.012) in the whole population. Conclusions: Skeletal muscle loss, after neoadjuvant chemoradiotherapy, negatively impacts on disease-free survival in surgically treated rectal cancer patients.     

辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌

 目的 探讨辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌的安全性和有效性。方法 22例T1 ~ T2c前列腺癌患者在采用直肠超声引导经会阴穿刺放射性125I粒子组织间植入治疗前后，给予辅助内分泌治疗4 ~ 7个月。术前2 ~ 4个月，术后1 ~ 4个月。结果 22例手术均顺利完成，手术时间60 ~ 120 min，植入125I粒子40 ~ 75枚，术后随访12 ~ 48个月，前列腺特异性抗原（PSA）＜1 ng／ml 15例，1 ng／ml≤PSA＜2 ng／ml 2例，PSA≥2 ng／ml 5例。结论 辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌安全有效     

Integrating hormonal therapy with external-beam radiation and brachytherapy for prostate cancer

The use of hormonal therapy with external-beam radiation (EBRT) to treat prostate cancer is a topic that has been well explored. The potential use of hormonal therapy and brachytherapy in the treatment of prostate cancer, however, continues to be controversial. This review is based on our current interpretation of the available literature assessing the outcomes of patients treated with EBRT and brachytherapy with or without hormonal therapy. Extrapolating from the findings of the Radiation Therapy Oncology Group (RTOG) 9413 trial, there appears to be a favorable interaction between hormonal therapy and irradiation in the lymph nodes. The benefits demonstrated with whole-pelvic EBRT and hormonal therapy are likely to extend to patients treated with brachytherapy as well. Studies suggest that the role of hormonal therapy in brachytherapy is limited without the application of whole-pelvic EBRT due to the inability of brachytherapy to address potential lymph nodes at risk. The potential role of hormonal therapy in conjunction with brachytherapy without pelvic radiotherapy, is limited by inconclusive data and abbreviated follow-up times.     

Changes in biomarkers of inflammation and angiogenesis during androgen deprivation therapy for prostate cancer

Introduction.

Angiogenesis and inflammation are both important to the pathogenesis of malignancies. Androgen deprivation therapy (ADT) for prostate cancer causes drastic hormonal changes that alter both disease and host factors. We measured inflammatory and angiogenic biomarkers in ADT-treated and control groups of men with prostate cancer.

Materials and Methods.

Baseline and 12-week plasma samples were collected from 37 ADT-naïve men with locally advanced or recurrent prostate cancer. Of those, 23 initiated ADT with a gonadotropin-releasing hormone (GnRH) agonist and 14 served as nontreatment controls. Samples were tested for a panel of angiogenic and inflammatory biomarkers.

Results.

The treatment group had significantly higher concentrations of the inflammatory biomarkers interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and stromal cell–derived factor (SDF)-1α. None of the angiogenic biomarkers were significantly different between the groups at baseline. Among patients with a short prostate-specific antigen (PSA) doubling time (<6 months), the proangiogenic factor basic fibroblast growth factor (bFGF) was lower at baseline. In the treatment group, plasma placental growth factor (PlGF) increased and IL-6 decreased after 12 weeks of ADT. Moreover, the treatment group continued to have significantly higher concentrations of the inflammatory biomarkers IL-1β, IL-8, and SDF-1α as well as bFGF than controls.

Discussion.

These men were characterized by elevations in several traditional markers of aggressive disease and also by higher levels of several inflammatory biomarkers. Although ADT decreased IL-6 levels, IL-1β, IL-8, and SDF-1α remained significantly higher than in controls. The role of these biomarkers should be further explored.     

Sarcopenia during androgen-deprivation therapy for prostate cancer

PURPOSE To characterize changes in lean body mass (LBM) in men with prostate cancer receiving androgen-deprivation therapy (ADT). PATIENTS AND METHODS We prospectively evaluated LBM in a prespecified substudy of a randomized controlled trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic prostate cancer. LBM was measured by total-body dual-energy x-ray absorptiometry at study baseline and at 12, 24, and 36 months. The analyses included 252 patients (132, denosumab; 120, placebo) with a baseline and at least one on-study LBM assessment. Patients were stratified by age (< 70 v ≥ 70 years) and by ADT duration (≤ 6 v > 6 months). Results Median ADT duration was 20.4 months at study baseline. Mean LBM decreased significantly from baseline, by 1.0% at month 12 (95% CI, 0.4% to 1.5%; P < .001; n = 248), by 2.1% at month 24 (95% CI, 1.5% to 2.7%; P < .001; n = 205), and by 2.4% at month 36 (95% CI, 1.6% to 3.2%; P < .001; n = 168). Men age ≥ 70 years (n = 127) had significantly greater changes in LBM at all measured time points than younger men. At 36 months, LBM decreased by 2.8% in men age ≥ 70 years and by 0.9% in younger men (P = .035). Men with ≤ 6 months of ADT at study entry (n = 36) had a greater rate of decrease in LBM compared with men who had received more than 6 months of ADT at study entry (3.7% v 2.0%; P = .0645). CONCLUSION In men receiving ADT, LBM decreased significantly after 12, 24, and 36 months.     

Obesity,body composition,and prostate cancer

Background  

Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10) prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA) to measure body composition and determine the association between prostate cancer and total body fat mass (FM) fat-free mass (FFM), and percent body fat (%BF), and which body composition measure mediated the association between BMI or waist circumference (WC) with prostate cancer.     

Depression related to (neo)adjuvant hormonal therapy for prostate cancer

Background

We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy.

Methods

Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient’s prognosis.

Results

During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small.

Conclusions

Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.