Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography

Background

The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging.

Objective

To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP.

Design, setting, and participants

Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan.

Intervention

Patients underwent salvage lymph node dissection (LND).

Measurements

Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively.

Results and limitations

Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses.

Conclusions

Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.     

Official Positions for FRAX Clinical Regarding Biochemical Markers: From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX

The best indirect evidence that increased bone turnover contributes to fracture risk is the fact that most of the proven therapies for osteoporosis are inhibitors of bone turnover. The evidence base that we can use biochemical markers of bone turnover in the assessment of fracture risk is somewhat less convincing. This relates to natural variability in the markers, problems with the assays, disparity in the statistical analyses of relevant studies and the independence of their contribution to fracture risk. More research is clearly required to address these deficiencies before biochemical markers might contribute a useful independent risk factor for inclusion in FRAX^®.     

Estimating treatment difference for binary responses in the presence of surrogate endpoints

Surrogate endpoint is chosen as a measure or indicator of a biological process that is obtained sooner, at less cost or less invasively than a true endpoint of health outcome, and is used to arrive at conclusions about the effect of intervention on the true endpoint. Following the work of Begg and Leung (J. R. Stat. Soc. Ser. A 2000; 163:15-28), we introduce a new motivation to analyse the surrogate and true endpoints together, to have a better estimate of the treatment difference where both the endpoints are binary. Several estimators are studied and compared. Some real data sets are analysed.     

道地药材评价模式研究

目的：探讨道地药材的评价模式。方法：研究道地药材的品种、产地、疗效、化学成分、栽培及产地加工等形成因素,并将这些因素作为评价道地药材的指标,按照指标比重给以相应的分数。结果与结论：为道地药材评价提供一种可量化或半量化的评价模式及方法。     

益肾补骨推拿法治疗骨质疏松症的实验方法探讨

本文根据“肾主骨”的中医理论,探讨了益肾补骨推拿法治疗骨质疏松症模型动物的实验方法.常用的模型制作方法包括卵巢摘除骨质疏松大鼠模型(OVX)、老年性骨质疏松大鼠模型和糖皮质激素诱发骨质疏松大鼠模型( GIOP),对这些造模成功的大鼠进行益肾补骨推拿法操作,观测大鼠骨密度(BMD)和骨代谢生化指标的变化.通过动物实验证实...     

生化检验结果异常的原因分析

目的:分析影响生化检验结果的一些重要因素,以期能加强检验过程的质量控制,提高本院生化检验质量与水平。方法:分析标本采集、生理因素和溶血对生化检验结果的影响,探究生化检验结果异常的原因。结果:通过检验人员专业学习的不断提高,采送符合要求的标本,发现异常结果需及时与临床沟通,了解患者情况,使检验水平不断提高。结论:通过分析得出:在日后临床与检验工作中,加强生化检验的质量控制,为临床提供具有参考意义与价值的报告。     

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone

Purpose

Intermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients.

Material and methods

Eighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7 mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA + 2 ng/mL.

Results

With a median follow-up of 51 months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ?2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity.

Conclusion

HyRT to a dose of 66 Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.     

Comparison of the effects of genistein and zoledronic acid on the bone loss in OPG-deficient mice

Using osteoprotegerin (OPG)-knockout mice, we demonstrated that in vivo the effects of both genistein and 17beta-estradiol (E2) on bone metabolism were completely abolished. In contrast, zoledronic acid could effectively suppress bone resorption and prevent bone loss. INTRODUCTION: The anti-resorptive effects of E2 on bone metabolism are considered to be mediated via modulation of the osteoblast-derived paracrine factor OPG. Recently, the phytoestrogen genistein was found to suppress bone resorption by enhancing osteoblastic production of OPG. However, the mechanism underlying the in vivo effects of E2 and genistein on bone is not entirely understood, and a central question in this regard is whether E2 regulates bone metabolism via an OPG-dependent pathway. METHODS: After mating heterozygous (OPG+/-) mice, homozygous (OPG-/-) and wild-type (WT) with a mixed C57BL/6J x 129/SV background were obtained. The study involved 6-week-old female OPG-/- (n=40) and WT mice (n=8). The OPG-/- mice were randomly divided into 5 groups (n=8 per group) as follows: (1) genistein-treated mice (Gen) that were subcutaneously injected with genistein at a maximal dose (0.8 mg/day); (2) E2-treated mice (E2) that were subcutaneously injected with E2 at a dose (0.03 microg/day); (3) DMSO control mice (DMSO) that were subcutaneously injected with a mixture of dimethylsulfoxide (DMSO) and polyethyleneglycol-300; (4) zoledronic acid-treated mice (Zol) that were subcutaneously injected with zoledronic acid at a dose of (150 microg/kg) twice per week; and (5) H2O control mice that were subcutaneously injected with sterilized water twice per week. The doses of genistein, estrogen and zoledronic acid were selected based on the results of dose-response effect of agents on bone versus uterus in OPG-/- mice. The mice were sacrificed 6 weeks after this intervention. The microarchitecture of the trabecular and cortical bone was assessed by performing microcomputed tomography (micro-CT) for the right proximal tibia. The bone mineral density (BMD) of the left femur was measured by dual-energy X-ray absorptiometry (DXA). The biomechanical parameters of the right femur were determined by a three-point bend testing. Serum levels of bone alkaline phosphatase (B-ALP), tartarate-resistant acid phosphatase-5b (TRACP-5b), and receptor activator of nuclear factor kappaB ligand (RANKL) were determined by performing ELISA. RESULTS: DXA analysis revealed that the total BMD of the femur was not significantly altered in the Gen, E2, H2O, and DMSO groups. The three-point bending test revealed no significant differences in the biomechanical parameters, including ultimate loading, ultimate stress, stiff index, and elastic modulus, and micro-CT analysis revealed that the microarchitectural parameters of the trabecular bone (vBMD, tBMD, BVF, BSF, SMI, Tb.N, Conn.D, Tb.Sp, and Tb.Th) and cortical bone (Ct.Th, Mm, In.Pm, Ot.Pm, Ma.Ar, Ct.Ar, Tt.Ar, Ct.BMD, and Ct.BMC) did not differ among the groups. Genistein and E2 treatment did not alter the serum TRACP-5b, B-ALP, or RANKL levels. However, in addition to increasing the bone mass, zoledronic acid could effectively improve biomechanical parameters and could completely prevent deterioration of the bone architecture in the OPG-/- mice. CONCLUSIONS: The effects of genistein and E2 on bone metabolism in vivo were lost completely in OPG-deficient mice, suggesting that the effect of these agents on bone metabolism seems to be entirely dependent on OPG. In contrast, zoledronic acid could effectively suppress bone resorption and completely prevent the bone loss in the OPG-/- mice--an effect that is likely to be independent of the OPG pathway.     

Radical Prostatectomy for Incidental (Stage T1a–T1b) Prostate Cancer: Analysis of Predictors for Residual Disease and Biochemical Recurrence

Background

Controversies exist about the most appropriate management for patients with incidental prostate cancer after surgery for benign prostatic hyperplasia (BPH).

Objectives

To test the accuracy of preoperative clinical variables in predicting the presence of residual disease and biochemical recurrence in patients with incidental prostate cancer treated with radical retropubic prostatectomy.

Design, Setting, and Participants

We analyzed 126 T1a–T1b prostate cancers diagnosed at surgery for BPH between 1995 and 2007.

Intervention

All patients underwent radical retropubic prostatectomy within 6 mo of surgery for BPH.

Measurements

Univariate and multivariate logistic regression models addressed the association between the predictors (age, prostate-specific antigen [PSA] before and after surgery for BPH, T1a–T1b stage, prostate volume, and Gleason score at surgery for BPH) and the presence of residual cancer at radical retropubic prostatectomy. Cox proportional hazards regression analyses tested the relationship between the same predictors and the rate of biochemical recurrence after radical retropubic prostatectomy.

Results and Limitations

Seventy-five (59.5%) patients were stage T1a and 51 (40.5%) were stage T1b. At radical retropubic prostatectomy, 21 (16.7%) patients were pT0 and seven (5.6%) patients had extraprostatic disease (pT3). PSA before and after surgery for BPH and Gleason score at surgery for BPH were the only independent predictors of residual cancer at radical retropubic prostatectomy (all p < 0.04). Stage (T1a vs T1b) did not predict residual cancer or the rate of biochemical recurrence. With a mean follow-up of 57 mo, the 5- and 10-yr biochemical recurrence-free survival rates were 92% and 87%, respectively. PSA after surgery for BPH and Gleason score at surgery for BPH were the only significant multivariate predictors of biochemical recurrence (all p < 0.04). The main limitation of this study is the requirement of an external validation before implementation of the clinical recommendations.

Conclusion

PSA measured before and after surgery for BPH and Gleason score at surgery for BPH were the only significant predictors of the presence of residual cancer at radical retropubic prostatectomy. PSA measured after surgery for BPH and Gleason score at surgery for BPH were the only independent predictors of biochemical recurrence after radical retropubic prostatectomy.     

PSA in the new millennium: a powerful predictor of prostate cancer prognosis and radical prostatectomy outcomes--results from the SEARCH database

OBJECTIVES: As a result of prostate-specific antigen (PSA) screening, most men today with prostate cancer present with localized disease and serum PSA values < 10 ng/ml. Within this context, it is debated whether PSA remains an important prognostic variable in more recently treated patients. We examined the prognostic significance of preoperative PSA to predict pathologic stage and biochemical progression among men undergoing radical prostatectomy in the new millennium (2000-2006). METHODS: We performed a review of 925 men with prostate cancer treated by radical prostatectomy since 2000 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We examined the association between preoperative PSA and risk of adverse pathologic features and biochemical progression using logistic regression and Cox proportional hazards analysis. RESULTS: After adjusting for multiple clinical preoperative characteristics, higher preoperative PSA values were associated with increased odds of extracapsular extension (p<0.001), positive surgical margins (p<0.001), and seminal vesicle invasion (p<0.001) and increased risk of biochemical progression (p=0.009). When the analyses were limited to the 690 men with a preoperative PSA<10 ng/ml and after adjusting for multiple clinical characteristics, higher preoperative PSA values remained associated with increased risk of biochemical progression (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.06-1.28, p=0.002). Even among the 448 men with a PSA<10 ng/ml and clinical stage T1c disease, preoperative PSA was associated with increased risk of biochemical progression (HR 1.14, 95%CI 1.00-1.31, p=0.047). CONCLUSIONS: PSA remains an important prognostic marker among men diagnosed with prostate cancer in the new millennium treated with radical prostatectomy and remains an important predictor of outcome even among men with preoperative PSA level < 10 ng/ml.