Ayako Masunaga

Prognostic value of neutrophil-to-lymphocyte ratio in patients with metastatic renal cell carcinoma treated with first-line and subsequent second-line targeted therapy: A proposal of the modified-IMDC risk model

PURPOSE The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model has been designed for prognostification in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. One factor is neutrophil count; however, increasing evidence has suggested the superiority of neutrophil-to-lymphocyte ratio (NLR) for predicting outcome. In this study, we evaluate the prognostic effect of NLR levels on patients with mRCC treated with targeted therapy, and then we compare the predictive accuracy of the IMDC risk model and its modified one by using NLR, instead of neutrophil count. PATIENTS AND METHOD A total of 277 patients are included for the analysis. All patients underwent targeted therapies and associated outcome are assessed using multivariate analysis. RESULTS Pretreatment NLR levels are elevated in 30.3% and 23.1% of patients in the first-line and subsequent second-line setting, respectively. Kaplan-Meier curves reveal that elevated pretreatment NLR is significantly associated with poor overall survival (OS) since first-line (P<0.001) and second-line targeted therapy administration (P<0.001). Also, multivariate analyses show that elevated pretreatment NLR is an independent predictor for poor OS since first-line and second-line targeted therapy administration. The addition of NLR to the IMDC risk model, instead of neutrophil count, significantly improves the predictive accuracy for OS, and estimated gain is 1.7% and 6.2% in first-line and second-line targeted therapy, respectively. CONCLUSION Changes in NLR levels could be predictive for prognosis in patients with mRCC treated with first-line and second-line targeted therapy. The addition of NLR significantly improves the predictive accuracy of the IMDC risk model in the first-line and subsequent second-line setting.

External Validation of the MSKCC and IMDC Risk Models in Patients Treated with Targeted Therapy as a First-line and Subsequent Second-line Treatment: A Japanese Multi-institutional Study

BACKGROUND Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy. OBJECTIVE To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy. DESIGN, SETTING, AND PARTICIPANTS A total of 311 patients were assessed retrospectively. INTERVENTION All patients underwent targeted therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Survival outcomes were assessed using Kaplan-Meier analysis. The predictive ability was evaluated using the c-index. RESULTS AND LIMITATIONS Regarding to the first-line targeted therapy, the 3-yr overall survival (OS) rates of the MSKCC (p<0.001) and IMDC models (p<0.001) were 76.2% and 77.3%, respectively, in the favorable-risk group; 46.7% and 47.9%, respectively, in the intermediate-risk group; and 13.4% and 15.6%, respectively, in the poor-risk group. The c-indexes were 0.68 for the MSKCC model and 0.69 for the IMDC model in a first-line setting. Regarding the second-line targeted therapy, the 1-yr OS rates of the MSKCC (p<0.001) and IMDC models (p<0.001) were 80.9% and 90.5%, respectively, in the favorable-risk group; 71.4% and 70.6%, respectively, in the intermediate-risk group; and 31.7% and 24.6%, respectively, in the poor-risk group. The c-indexes were 0.66 for the MSKCC model and 0.65 for the IMDC model in the second-line setting. The study is limited by its retrospective nature. CONCLUSIONS The results may assist physicians in providing more appropriate patient counseling and imply the need for a future prognostic tool in mRCC treated with targeted therapy. PATIENT SUMMARY Both risk models were useful for the risk stratification in metastatic renal cell carcinoma (mRCC) patients treated with first-line and second-line targeted therapy; however, it might be necessary to further update or optimize the models for our Japanese cohort of mRCC patients.

Effect of reclassification of the IMDC model in patients with metastatic renal cell carcinoma treated with targeted therapy in the first-line and second-line settings

PURPOSE To investigate the prognostic effect of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model reclassification after targeted therapy administration in metastatic renal cell carcinoma (mRCC). PATIENTS AND METHOD A total of 245 mRCC patients treated with targeted therapy are included. The IMDC model reclassification is performed at 1 month after treatment induction of both first-line and second-line targeted therapy. RESULTS Of the 245 patients, 74 (30.2%) are divided into different risk groups by the IMDC model reclassification after first-line targeted therapy, and patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.018). Of the 119 patients treated with subsequent second-line targeted therapy, 25 (21.0%) are divided into different risk groups by the IMDC model reclassification after second-line targeted therapy, and patients newly classified with poor risk tend to have increased all-cause mortality compared with those remaining in the primary intermediate-risk group (P = 0.007), whereas patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.034). CONCLUSION Approximately a quarter of the mRCC patients are classified into different risk groups of the IMDC model following targeted therapy administration in the first-line and second-line settings. There is a significant difference in overall survival of subgroups after the IMDC model reclassifications.

Do Transurethral Treatments Increase the Complexity of Urethral Strictures

Purpose: We examined the impact on urethral stricture complexity at urethroplasty of previous transurethral treatments such as dilation, urethrotomy and stenting, which are most commonly performed when treating male urethral stricture. Materials and Methods: We retrospectively reviewed the records of 45 males who had undergone transurethral treatments before urethroplasty. We compared urethrography findings at initial diagnosis with those at urethroplasty. Males with failed hypospadias repair, lichen sclerosis or a history of prior urethroplasty were excluded from analysis. We considered stricture complexity increased if the number and/or length of strictures on urethrography at urethroplasty was greater than that at initial diagnosis or false passage was newly identified. Results: Of the patients 39 (87%), 32 (71%) and 13 (29%) had undergone urethral dilation, urethrotomy and urethral stenting, respectively, and 39 (87%) had undergone repeat or multiple kinds of transurethral treatments. Stricture complexity was increased in 22 men (49%) while 7 (16%) required urethroplasty more complex than that anticipated from urethrography findings at initial diagnosis. Increased stricture complexity was significantly associated with a history of urethrotomy (p = 0.03), urethral stenting (p = 0.0002) and repeat transurethral treatments (p = 0.01). Multivariate analysis revealed that urethral stenting (p = 0.01) and repeat transurethral treatments (p = 0.01) were independent predictors of increased stricture complexity. Conclusions: Repeat transurethral treatments increase stricture complexity and are potentially counterproductive. Even a single application of temporary urethral stenting carries a high risk of complicating the stricture and requiring complex urethroplasty.

Primary Realignment for Pelvic Fracture Urethral Injury Is Associated With Prolonged Time to Urethroplasty and Increased Stenosis Complexity

OBJECTIVE To compare the clinical courses of patients with pelvic fracture urethral injury (PFUI) according to initial management strategy. METHODS We reviewed the clinical courses of 63 patients with PFUI who were initially treated elsewhere and underwent delayed anastomotic urethroplasty by a single surgeon between 2008 and 2015. Patients were grouped according to their initial treatment: by suprapubic tube placement alone (49 patients, SPT group) or primary realignment (14 patients, PR group). Time to urethroplasty was defined as the period between injury and delayed urethroplasty. Clinical data regarding the status of urethral stenosis, urethroplasty procedure, and treatment outcome were analyzed. RESULTS The mean time to urethroplasty in the PR group was about 3 times than that in the SPT group (133 months vs 47 months, P = .035). Fifty percent of the PR group (7 of 14) had a history of repeated urethrotomy or dilation before referral, a percentage significantly higher than that of the SPT group (20.4%, 10 of 49, P = .027). The percentage of patients having a false passage and iatrogenic scar was significantly higher in the PR group (42.9% vs 16.3%, P = .035), but there was no significant between-group difference in urethral stenosis length, operative time, operative blood loss, or the percentage of patients requiring inferior pubectomy or urethral rerouting. CONCLUSION PR does not facilitate delayed urethroplasty, and patients who undergo PR are at high risk of having a more complicated stenosis and longer time to urethroplasty, presumably because of repeated transurethral procedures.

Clinical outcomes of percutaneous radiofrequency ablation for small renal cancer

Partial nephrectomy is the treatment of choice for small renal cell carcinoma (RCC) from the perspective of cancer management and renal function. However, when patients with RCC are of advanced age, exhibit severe comorbidities, including cardiovascular and pulmonary diseases, or have hereditary RCC, ablative therapies, including radiofrequency ablation (RFA) and cryoablation are useful treatment options. In the present study, the clinical outcomes of percutaneous RFA for treating small RCC were evaluated. Between December 2005 and March 2015, 40 patients (41 renal tumors in total) underwent RFA and a total of 50 sessions of RFA were performed. The average tumor size was 2.5 cm. A total of 18 tumors were exophytic and 23 were parenchymal. Of the 41 tumors, 85.4% were completely ablated by initial RFA and the rate of complete ablation following reablation for residual viable lesions was 95.1%. Local recurrence-free survival following complete ablation was 84.2% at 3 years. A patient with a 4.7 cm RCC tumor rapidly progressed following four RFA treatments until complete ablation was achieved. The metastasis-free survival rate following initial RFA was 95.7% at 3 years. The RCC-specific survival was 100% (mean follow-up, 38 months). Adverse events occurred in five sessions (10%); however, only 1 patient with arteriovenous fistula required intervention (transarterial embolization). The mean hospital stay following RFA was 3.2 days. The mean decrease in estimated glomerular filtration rate following RFA was 2.7%. The results of the present study indicate that percutaneous RFA was an effective treatment for small RCCs with respect to management of cancer, minimal invasiveness and minimal loss of renal function, particularly in patients for whom surgery would be a high risk and those at increased risk of deterioration of renal function.

Pubourethral Stump Angle Measured on Preoperative Magnetic Resonance Imaging Predicts Urethroplasty Type for Pelvic Fracture Urethral Injury Repair

OBJECTIVE To examine whether the type of delayed urethroplasty required for pelvic fracture urethral injury, which is not easily predicted from conventional urethrography findings, can be predicted from preoperative magnetic resonance imaging (MRI) results. PATIENTS AND METHODS Records of 74 male patients with pelvic fracture urethral injury who underwent MRI of the pelvis at least 3 months after injury and, subsequently, delayed anastomotic urethroplasty were retrospectively analyzed. Pubourethral stump length (PUL) was defined as the distance between the distal end of the proximal urethral stump and the lower border of the inferior pubic ramus. Pubourethral stump angle (PUA) was defined as the angle between the long axis of the pubis and the line between the distal end of the proximal urethral stump and the lower border of the inferior pubic ramus. Both PUL and PUA were measured in sagittal T2-weighted MRI. RESULTS Delayed urethroplasty was performed by a simple perineal approach in the 28 patients requiring only bulbar urethral mobilization with or without corporal splitting and by elaborate approach in the 46 additionally requiring inferior pubectomy or an abdominoperineal approach with urethral rerouting. The overall success rate defined as no recurrent stricture on urethroscopy was 94.6%. Disruption at the prostate apex, greater urethral gap length, longer PUL, and lower PUA were in univariate analysis significantly associated with an elaborate approach. In multivariate analysis, only low PUA was an independent predictor of the need for an elaborate approach. CONCLUSION PUA measured on MRI is useful for predicting the type of reconstruction needed for urethral repair.

MP16-07 USEFULNESS OF INFLAMMATORY MARKER DYNAMICS ONE MONTH AFTER THE FIRST-LINE TARGETED THERAPY INITIATION FOR PFS PREDICTION IN PATIENTS WITH METASTATIC CLEAR CELL RENAL CELL CARCINOMA

Keiichi Ito*, Ayako Masunaga, Saitama, Japan; Nobuyuki Tanaka, Ryuichi Mizuno, Tokyo, Japan; Suguru Shirotake, Yota Yasumizu, Hidaka, Japan; Yujiro Ito, Yasumasa Miyazaki, Tokyo, Japan; Masayuki Hagiwara, Ichikawa, Japan; Kent Kanao, Nagakute, Japan; Shuji Mikami, Tokyo, Japan; Tetsuo Monma, Wako, Japan; Ken Nakagawa, Ichikawa, Japan; Tsuyoshi Masuda, Saitama, Japan; Masafumi Oyama, Hidaka, Japan; Tomohiko Asano, Saitama, Japan; Mototsugu Oya, Tokyo, Japan