Tumor growth velocity: A modified tumor growth rate defining tumor progression during sorafenib treatment in patients with metastatic renal cell carcinoma.

OBJECTIVES: To investigate the role of tumor growth velocity in defining tumor progression in metastatic renal cell carcinoma patients treated with the vascular endothelial growth factor tyrosine kinase inhibitor, sorafenib. METHODS: A modified calculation for tumor growth velocity was introduced to evaluate the tumor growth velocity, before and after sorafenib withdrawal. Known prognostic factors together with tumor growth velocity before drug withdrawal and tumor growth velocity after drug withdrawal were compared using a χ2 -test from a contingency table, and partial likelihood test from a Cox regression model for overall survival. RESULTS: A total of 114 patients who reached progressive disease and withdrew from sorafenib were enrolled after a median follow-up period of 107.8 months. Tumor growth velocity before drug withdrawal was 7.347 ± 4.040, and tumor growth velocity after drug withdrawal was 11.647 ± 5.937 (P < 0.001). Higher tumor growth velocity before drug withdrawal was correlated with a higher risk Memorial Sloan Kettering Cancer Center score (P = 0.022), Karnofsky Performance Status <80 (P = 0.028), non-clear cell carcinoma (P = 0.037), higher tumor nucleus grade (P < 0.001) and best treatment response (P < 0.001). Patients with tumor growth velocity before drug withdrawal >5.0 had shorter overall survival (P < 0.001). On multivariate analysis, factors associated with overall survival were high/intermediate Memorial Sloan Kettering Cancer Center risk score (hazard ratio 2.119, P = 0.006), non-clear histological subtype (hazard ratio 1.900, P = 0.031), tumor growth velocity before drug withdrawal ≥5.0 (hazard ratio 2.758, P < 0.001) and progressive disease as best response (hazard ratio 2.069, P = 0.001). CONCLUSIONS: Significantly faster tumor growth can be observed if sorafenib is discontinued in the case of disease progression. Thus, we suggest not to withdraw targeted agents until tumor growth velocity is >5.0.

Cost analysis for different sequential treatment regimens for metastatic renal cell carcinoma in China.

PURPOSE: Targeted therapies, including sunitinib, sorafenib, axitinib, and everolimus, have recently become the mainstay for the treatment of metastatic renal cell carcinoma (mRCC). The objective of this study was to estimate the costs of sequential treatment regimens for mRCC and associated adverse events (AEs) from the Chinese payers' perspective. METHODS: Key inputs included in the calculation were patient population, dosing information, incidence rates and associated costs of Grade 3/4 AEs, treatment costs (including drug discount programs), and patients' progression-free survival (PFS) as a proxy for length of treatment. To calculate PFS, this study identified pivotal clinical trials and generated a reconstructed individual patient data set from the published Kaplan-Meier survival curves. The median PFS from the pooled estimates were used in the calculation. In the base-case scenario, sunitinib was used as first line and the other three therapies were used as second line. Sensitivity analyses were conducted where (1) sorafenib was used as first line, or (2) a third-line therapy was added to the base-case scenario. RESULTS: In the base case, the cost per patient per treatment month (PPPM) cost was the lowest for sunitinib + axitinib among all sequential regimens (¥14,898) and was the highest for sunitinib + sorafenib (¥20,103). If sorafenib is used as first line, everolimus had lower per patient per months (PPPM) cost than axitinib (¥17,046 vs ¥23,337), but also had shorter PFS (13.5 months vs 15 months). Second sensitivity analysis with an additional third-line therapy showed consistent results with the base-case scenario; axitinib as second line was the least costly. CONCLUSIONS: This study demonstrates that, for mRCC sequential treatment, sunitinib followed by axitinib generates the highest cost savings from the Chinese payers' perspective. Future studies are warranted to examine the cost-effectiveness of various mRCC treatment regimens in Chinese populations.

Eosinophil percentage elevation as a prognostic factor for overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor.

BACKGROUND: We tried to investigate the prognostic significance of post-treatment eosinophil percentage(Eo %) in metastatic renal cell carcinoma(mRCC) patients undertaking sorafenib. RESULTS: The median OS for the entire sorafenib treatment period was 21.9 months (95% CI: 17.2-25.9 months). Of the 282 mRCC patients, 101 patients experienced an elevated post-treatment Eo % within two months. Median OS of post-treatment Eo % elevated group and non-elevated group were 42.9 months and 16.8 months(p=0.000). After adding post-treatment Eo % into a modified MSKCC model or Heng's model, 43 and 41 patients were reclassified into favorable group, 5 and 9 patients were reclassified to intermediate group respectively. METHODS: mRCC patients treated with sorafenib from 2006 to 2015 in were evaluated. Pre- and post-treatment Eo % were assessed. Oncologic outcomes were analyzed by overall survival and tumor response rate. Predictive parameters were assessed in a Cox proportional hazard model. CONCLUSIONS: Our study demonstrates that an early elevation of Eo % after sorafenib treatment is a strong predictor of good prognosis. Eo % can be a good supplementary for prognostic models using pre-treatment parameters.

Prognostic value of pathological features of primary lesion in metastatic renal cell carcinoma treated with sorafenib.

AIM: This study aimed to investigate whether the pathological features of primary lesions show additional prognostic value in patients with metastatic renal cell carcinoma who are treated with sorafenib. PATIENTS & METHODS: A consecutive cohort of 284 patients was included from Fudan University Shanghai Cancer Center between 2007 and 2013. The association between survival and pathological features of primary tumors was assessed using the Cox proportional hazards model. The incremental value of prognostication was evaluated. RESULTS: We found that the pathological features of primary lesions provided added prognostic value over the Memorial Sloan-Kettering Cancer Center model in patients with metastatic renal cell carcinoma who were treated with sorafenib. CONCLUSION: Addition of a pathological score in the clinical setting could better identify patients at risk of poor survival.

Impact of preoperative 5α-reductase inhibitors on perioperative blood loss in patients with benign prostatic hyperplasia: a meta-analysis of randomized controlled trials.

BACKGROUND: The ability of 5α-reductase inhibitors (5ARIs) to decrease blood loss during transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) remains controversial. We aimed to conduct a meta-analysis of all randomized controlled trials (RCTs) to establish the role of 5ARI use prior to TURP. METHODS: We searched studies from the electronic databases PubMed, Embase, Scopus, and Cochrane Library from inception to March 25, 2014. Meta-analysis was performed using the statistical software Review Manager version 5.1. RESULTS: Seventeen RCTs including 1489 patients were examined. We observed that preoperative treatment with finasteride can decrease total blood loss, blood loss per gram of resected prostate tissue, hemoglobin level alteration, microvessel density (MVD), and vascular endothelial growth factor level. Neither finasteride nor dutasteride reduced operative time, prostate volume, or the weight of gland resected. In contrast, pretreatment with dutasteride before TURP did not decrease the total blood loss or MVD. CONCLUSIONS: Pretreatment with finasteride does seem to reduce perioperative blood loss related to TURP for BPH patients. However, the effect of preoperative dutasteride was inconclusive. Further studies are required to strengthen future recommendations regarding the use of 5ARI as a standard pre-TURP treatment and its optimal regimen.

c-KIT: potential predictive factor for the efficacy of sorafenib in metastatic renal cell carcinoma with sarcomatoid feature.

BACKGROUND: Vascular endothelial growth factor-targeted therapy has been standard care for metastatic renal cell carcinoma for years. However, little clinical experience on these agents in the treatment of sarcomatoid tumors has been documented. The aim of the present study was to detect the expression of c-KIT in the primary tumor of metastatic renal cell carcinoma with sarcomatoid feature, and to reveal its potential value of predicting the efficacy of sorafenib treatment and survival of the patients. PATIENTS AND METHODS: Seventeen patients were enrolled and treated with sorafenib as a second-line treatment after cytokine therapy. The expressions of c-KIT was tested immunohistochemically in the 17 specimens of primary renal tumors. The correlation between c-KIT status and treatment effect was compared. Univariate and multivariate analysis were employed to determine the survival difference between c-KIT-positive and c-KIT-negative patients. RESULTS: Twelve of 17 specimens (70.6%) were detected to be overexpressing c-KIT. c-KIT positive patients had higher disease control rate (75%) compared with c-KIT-negative patients (25%), P = .036. Median overall survival time was 92 weeks for c-KIT positive patients and 44 weeks for c-KIT negative patients, log rank χ(2) = 9.566, P = .002. Multivariate Cox regression model analysis only revealed number of metastatic organs and c-KIT as independent prognostic factors. CONCLUSION: Our findings suggest that c-KIT can be a potential predictive factor for metastatic renal cell carcinoma with sarcomatoid feature in treatment using sorafenib, and patients with positive c-KIT expression might have better responses and obtain longer overall survival time.

Tumor cytoreduction results in better response to androgen ablation--a preliminary report of palliative transurethral resection of the prostate in metastatic hormone sensitive prostate cancer.

OBJECTIVES: To investigate the oncologic influence of transurethral resection of the prostate (TURP) as a cytoreductive surgery in metastatic hormone sensitive prostate cancer (mHSPC), in the setting of continuous complete androgen blockade (CAB). MATERIALS AND METHODS: Medical histories of 146 consecutive Chinese males with newly diagnosed mHSPC, registered in our institution in 2006 and 2007, were reviewed. All of these patients received CAB as initial systematic therapy. Demographics and cancer control outcomes from 39 mHSPC patients who underwent TURP for a relief of bladder outlet obstruction were compared with those of the other 107 who received CAB only when they were still hormone-sensitive. Median follow-up was 15 months (3 to 27 months). RESULTS: Age at diagnosis, baseline PSA, and biopsy Gleason score were comparable between the 2 groups. Patients who underwent a TURP had lower PSA nadir (median 0.15 ng/ml vs. 0.82 ng/ml, P = 0.015) and longer time to PSA nadir (11.2 months vs. 6.4 months, P < 0.001). More patients in the non-TURP group developed hormone refractory prostate cancer (P = 0.007). The TURP group had a tendency towards longer disease-specific survival and overall survival (24.4 months vs. 24.1 months and 24.4 months vs. 22.9 months, respectively), though this did not reach statistical significance. CONCLUSIONS: TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted.

Erythrocyte sedimentation rate kinetics as a marker of treatment response and predictor of prognosis in Chinese metastatic renal cell carcinoma patients treated with sorafenib.

OBJECTIVES: Previous prognostic factor models for metastatic renal cell carcinoma (mRCC) have not included erythrocyte sedimentation rate (ESR). We designed the present study to evaluate the prognostic value of ESR for mRCC patients treated with sorafenib. METHODS: Sorafenib was given to 83 patients with clear cell mRCC. Serum ESR was tested before treatment and every 4 weeks after first administration of sorafenib. Oncological evaluation was carried out every 8 weeks. Analyzed factors included age, sex, performance status, method of nephrectomy, number of metastatic organs, anemia, lactate dehydrogenase, corrected calcium, albumin, baseline ESR level and ESR kinetics status. Kaplan-Meier and Cox regression analyses on progression-free survival (PFS) were carried out. RESULTS: Baseline ESR levels ranged from 3 to 154 mm/h, and 43 (41.0%) patients had an ESR level higher than 40 mm/h. Median PFS was 10.0 months (95% CI 7.6-12.4 months). Dividing the cohort into three groups according to ESR kinetics status, median PFS was 27 months in the decreased ESR group, 12 months in the stable ESR group and 6 months in the increased ESR group. Performance status, time from diagnoses to sorafenib treatment, number of metastatic organs and ESR kinetics were independent predictors for PFS in multivariable Cox regression model analysis, with an area under the curve of 0.865 in a binary logistic regression model of 12-month PFS probability. CONCLUSIONS: ESR kinetics can be useful to monitor the treatment response and to predict PFS for mRCC patients treated with sorafenib as second-line therapy.

[The study of electrical acupuncture stimulation therapy combined with pelvic floor muscle therapy for postprostatectomy incontinence].

OBJECTIVE: To explore the effectiveness and significance of whether electrical acupuncture stimulation combining with pelvic floor muscle therapy (PFMT) can improve the recovery of urinary continence. METHODS: A total of 109 patients took part in the study of novel combination treatment for urinary continence from September 2008 to September 2009. Patients were divided into study group (n = 40) and control group (n = 69). The patients in study group received electrical acupuncture stimulation therapy combined with PFMT one week after removal the catheter. The patients in control group performed PFMT as the only treatment for post prostatectomy incontinence. The patients were followed up closely, with their clinical characteristics recorded, questionnaires of ICI-Q-SF filled up, and all the data for statistical analysis collected. RESULTS: There was a significant difference between the study group and the control group in the urinary control curve (P = 0.029). The difference of continence probability between these two groups became greater from 4 weeks after surgery, and the difference reached the peak at 6 weeks (P = 0.023). Then the difference became smaller, and there was no difference at 16 weeks after surgery. ICI-Q-SF questionnaires showed the same results. CONCLUSION: Electrical acupuncture stimulation therapy combining with PFMT can improve the recovery of patients' urinary continence after radical prostatectomy.

Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report.

INTRODUCTION: We describe our experience with sorafenib and sunitinib in the treatment of chemotherapy-refractory advanced penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: Between May 2008 and June 2009, 6 advanced penile cancer patients were treated with sorafenib or sunitinib in our center. All of them had previously received at least two chemotherapy regimens. Tumor responses were evaluated by radiologic assessment and serum SCC antigen change. Immunohistochemical staining of CD34 and Ki-67 was performed in 3 paired tumor tissues before and after treatment. RESULTS: In the 6 patients, 1 partial response and 4 stable diseases were observed. Three patients showed pain response and had an improvement in quality of life. After molecular-targeted therapies, reduction in microvessel density and Ki-67 labeling index was observed in paired specimens. Serum SCC antigen levels were decreased in 5 patients after 1 week of medication. The patient who achieved partial response had an SCC antigen reduction of nearly 95% after treatment with sunitinib. Serious adverse events were fatal infection and rupture of the femoral vessel, which were unlikely related to the medication. CONCLUSIONS: The feasibility and activity of sorafenib and sunitinib in our series suggest that this approach may be a promising alternative in chemotherapy-refractory advanced penile SCC.