Nozomi Hayakawa

The Predictive Value of C-reactive Protein for Prognosis in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Multi-institutional Study

BACKGROUND Few studies have discussed the prognostic impact of serum C-reactive protein (CRP) level in upper tract urothelial carcinoma (UTUC). OBJECTIVE To investigate whether the perioperative level of CRP provides additional prognostic information following radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS A total of 564 patients with UTUC from a retrospective multi-institutional cohort were included. The median follow-up was 32 mo. INTERVENTION All patients underwent RNU without neoadjuvant chemotherapy, while 106 patients (18.8%) received adjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations between perioperative CRP level and outcome were assessed using multivariate analysis. A serum CRP level >0.50mg/dl was defined as elevated. RESULTS AND LIMITATIONS Preoperative CRP (pre-CRP) level was elevated in 136 patients (24.1%). Multivariate analysis showed that pre-CRP elevation was an independent predictor of subsequent disease recurrence (hazard ratio [HR]: 1.47 for CRP 0.51-2.00; HR: 1.89 for CRP >2.00). Five-year recurrence-free survival rates were 69.2% in patients with pre-CRP levels ≤ 0.50 mg/dl, 54.3% in patients with pre-CRP levels between 0.51 and 2.00 mg/dl, and 35.4% in patients with pre-CRP levels >2.00 mg/dl (p<0.001). Similar results were found in cancer-specific mortality, showing that pre-CRP elevation was an independent predictor of worse outcome (HR: 1.74 for CRP 0.51-2.00; HR: 2.31 for CRP >2.00). In a subgroup analysis of the elevated pre-CRP group, postoperative normalisation of CRP level was an independent predictor of better outcome. This study is limited by its retrospective nature as well as its heterogeneous group of patients and variable follow-up protocols resulting from the multi-institution design. CONCLUSIONS Serum CRP may become a possible biomarker in UTUC, suggesting that patients with an elevated pre-CRP level could be predicted to have subsequent disease recurrence and cancer-specific mortality, while postoperative normalisation of CRP level was an independent predictor for prognosis.

Prognostic value of plasma fibrinogen levels in patients with localized upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is relatively uncommon, accounting for only ∼5% of urothelial malignancies and 10% of all renal tumours. Radical nephroureterectomy (RNU) with bladder cuff excision is the surgical standard of care for treating localized UTUC, but the prognosis for patients who undergo RNU remains poor. Evidence suggests that an interactive relationship exists between haemostatic factors and tumour biology. A number of procoagulant and fibrinolytic factors have been found to be overexpressed in tumours. One of these factors is plasma fibrinogen. Recent studies have shown that elevated pre‐therapeutic plasma fibrinogen levels are associated with worse outcome in various malignancies; however, the prognostic value of plasma fibrinogen levels for UTUC has not yet been reported. To the best of our knowledge, this is the first paper to evaluate the prognostic impact of preoperative plasma fibrinogen levels in patients with localized UTUC treated surgically. We believe that the present results may assist in decision‐making with respect to the need for lymph node dissection and neoadjuvant chemotherapy.

Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy: the experience of Japanese multi‐institutions

To investigate oncological outcomes and prognostic factors in patients with upper tract urothelial carcinoma (UTUC) who experienced disease recurrence after radical nephroureterectomy (RNU). Few studies have focused on the clinical courses of patients who experienced disease recurrence after RNU.

The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: A multi-institutional study1

BACKGROUND AND OBJECTIVE Few studies have addressed the predictive value of positive urine cytology for prognosis in patients with upper tract urothelial carcinoma (UTUC). We investigated whether the status of preoperative urine cytology could provide additional prognostic information following radical nephroureterectomy (RNU). MATERIALS AND METHODS The study included 474 patients with primary nonmetastatic UTUC (pTa-4N0M0) from a retrospective multi-institutional cohort. The median follow-up period was 35 months. Associations between the status of urine cytologic evaluation and outcomes were analyzed using multivariate Cox regression models. Urine cytology was evaluated preoperatively using voided samples. Disease recurrence was defined as any relapse in nonbladder lesions and was coded separately from intravesical recurrence. RESULTS Positive urine cytology was detected in 184 patients (38.8%) preoperatively. Disease recurrence occurred in 127 patients, while intravesical recurrence occurred in 219 patients; 83 patients died of UTUC during follow-up. Kaplan-Meier analysis revealed that only the incidence of intravesical recurrence was significantly associated with the status of urine cytologic evaluation (P = 0.024); the intravesical recurrence-free survival rates at 1 and 3 years following RNU were 61.4% and 46.2% in patients with positive urine cytology and 71.1% and 51.6% in their counterparts, respectively. Multivariate analysis showed that gender (hazard ratio [HR] = 1.74, 95% confidence interval [CI]; 1.28-2.43), tumor multifocality in RNU specimens (HR = 1.64, 95% CI; 1.09-2.47), and positive urine cytology (HR = 1.41, 95% CI; 1.08-1.85) were independent risk factors for subsequent intravesical recurrence. CONCLUSIONS The results showed the prognostic value of positive urine cytology in patients with primary UTUC, and preoperative positive urine cytology may be associated with a significant increase in the prevalence of intravesical recurrence following RNU.

C-reactive protein: A biomarker of survival in patients with localized upper tract urothelial carcinoma treated with radical nephroureterectomy

BACKGROUND AND OBJECTIVE Serum C-reactive protein (CRP) is one particular marker of systemic inflammation, and an elevated CRP level is associated with poor outcome in various malignancies. While the clinical value of CRP levels in upper tract urothelial carcinoma (UTUC) has not yet been fully evaluated, we investigated the impact of CRP elevation as a biomarker of patient prognosis in UTUC. MATERIALS AND METHODS A total of 183 patients who underwent radical nephroureterectomy (RNU) for localized UTUC (pTa-4N0M0) were identified between 1993 and 2009. The associations between the levels of serum CRP and patient outcome were analyzed. RESULTS Thirty-three patients experienced disease recurrence, and 28 died of the disease during the median follow-up period of 39 months. Using the defined cutoff level of CRP >0.5 mg/dl as elevated, preoperative CRP (pre-CRP) levels were elevated in 42 patients (23.0%). Kaplan-Meier curves revealed that subsequent tumor recurrences and worse cancer-specific survival could be significantly predicted in the elevated pre-CRP group. The 5-year recurrence-free survival rate was 63.6% in the elevated pre-CRP group and 83.4% in their counterparts (P < 0.001), and the 5-year cancer-specific survival rate was 64.7% in the elevated pre-CRP group and 84.3% in their counterparts (P = 0.001). Multivariate analysis revealed that elevated pre-CRP, in addition to pathologic T stage, was an independent risk factor for subsequent disease recurrence (P = 0.003, hazard ration (HR) = 2.83), and the decrease in cancer-specific survival (P = 0.012, HR = 2.65). In subgroup analysis using patients with pT3 tumors or greater, multivariate analysis also showed that elevated pre-CRP was an independent risk factor for a decrease in both recurrence-free and cancer-specific survival. CONCLUSIONS Pre-CRP level was an independent predictor of patient survival in localized advanced UTUC. Patients with pre-CRP >0.5 mg/dl were strongly predicted to have worse prognostic outcomes following RNU. Due to its low cost and easy accessibility, CRP may be a useful biomarker for localized UTUC.

Risk of subsequent tumour recurrence and stage progression in bacille Calmette-Guérin relapsing non-muscle-invasive bladder cancer

Study Type – Therapy (case series)

Comparison of outcomes between ultrasonography and cystoscopy in the surveillance of patients with initially diagnosed TaG1-2 bladder cancers: A matched-pair analysis

PURPOSE To examine the clinical outcomes of regular use of ultrasonography when compared with those of cystoscopy in the follow-up of patients with TaG1-2 bladder tumors. PATIENTS AND METHODS Between 1990 and 2012, 197 patients with TaG1-2 bladder tumors from a retrospective 2-institution cohort were included. We assessed clinical outcomes in 83 patients followed up by ultrasonography, matched for propensity score calculated from clinicopathological variables including age, gender, tumor multiplicity, size, grade, postoperative immediate chemoinstillation, and adjuvant intravesical treatment. RESULTS Among the 166 patients identified using the one-to-one propensity score analysis, the 5- and 10-year recurrence-free survival rates were both 63.3% in the cystoscopy group and 69.1% and 58.4%, respectively, in the ultrasonography group (P = 0.762). A total of 54 patients experienced disease recurrence, and 18 patients acquired progressive disease such as tumor grade 3, pT1 tumors, and the appearance of concurrent carcinoma in situ. There were no significant differences in the characteristics of recurrent tumors between both the groups, whereas time to first recurrence in the cystoscopy group was significantly shorter than that in the ultrasonography group (P = 0.021). In a subgroup analysis using 111 patients without adjuvant intravesical treatments, the 5- and 10-year recurrence-free survival rates were both 56.9% in the cystoscopy group and 71.9% and 60.3%, respectively, in the ultrasonography group (P = 0.282). CONCLUSIONS This retrospective study suggests that ultrasonography may be one of the follow-up substitutes when considering the management of low-risk bladder tumors such as TaG1-2 bladder tumors.

Impact of Combined Use of Blood-based Inflammatory Markers on Patients with Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Proposal of a Cumulative Marker Score as a Novel Predictive Tool for Prognosis

BACKGROUND Previous studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices. OBJECTIVE To investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS A total of 394 patients from multiple institutions were included. Median follow-up was 30 mo. INTERVENTION All patients underwent RNU without neoadjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP. RESULTS AND LIMITATIONS Multivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature. CONCLUSIONS Although the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU. PATIENT SUMMARY Elevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two.

The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guerin: A retrospective single centre study, and systematic review of the literature.

INTRODUCTION This retrospective study was undertaken to evaluate the combined effect of immediate intravesical chemotherapy and subsequent bacillus Calmette-Guérin (BCG) therapy. METHODS The study population consisted of 207 intermediate- or high-risk patients with non-muscle invasive bladder cancer who underwent an induction course of BCG between 1993 and 2007. We introduced single immediate instillation of 50 mg epirubicin for all cases in 2004, and thus earlier cases could be considered as historical controls. The primary endpoint was recurrence-free survival (RFS). For cumulative analysis, we systematically reviewed studies indexed in databases. Including ours, the records of 856 patients from a total of 7 studies, including ours, were finally analyzed. RESULTS In our cohort, the 5-year RFS in patients who received the combination therapy was 66.2%, compared to 55.2% in the BCG alone group (p = 0.149). Multivariate analysis on tumour recurrence showed that patients with the combination therapy had a hazard ratio (HR) of 0.74 (p = 0.189). A subsequent literature review revealed that RFS rates in the combination groups were higher than those in the corresponding BCG alone groups in 4/7 studies (p = 0.02-0.15), and lower in 1 study (p = 0.51). We identified 5 studies which examined a HR for combination therapy, and performed a cumulative analysis. Adding a single chemo-instillation prior to BCG resulted in a significant reduction in tumour recurrence (summary HR 0.69, p = 0.010). CONCLUSIONS Our analysis suggested that the combination of single chemo-instillation with subsequent BCG therapy exhibited an additive effect against potential tumour recurrence.

Preoperative parameters to predict incidental (T1a and T1b) prostate cancer

INTRODUCTON Prostate cancer has been found incidentally in transurethral resection of the prostate (TURP) specimens without prior diagnosis in 5% to 13% of the patients. We evaluated whether incidental prostate cancer (stages T1a and T1b) could be predicted preoperatively. METHODS TURP was performed in 307 patients between 2006 and 2011. Patient age, prostate-specific antigen (PSA) level, total prostate volume, transitional zone volume, PSA density, history of needle biopsy, and pathological diagnosis on TURP specimen were assessed. We analyzed the association between these parameters and prostate cancer detection. RESULTS Incidental prostate cancer was found in 31 patients (10.1%), and 13 cases (4.2%) had cancer with T1b and/or Gleason ≥7. Multivariate analysis demonstrated that age ≥75 years (odds ratio [OR] 2.58, p = 0.022), prostate volume ≤50 cc (OR 4.11, p < 0.001), and the absence of preoperative needle biopsy despite PSA ≥4 ng/mL (OR 2.65, p = 0.046) were independent risk factors. In patients who had 2 or 3 of these risk factors, incidental prostate cancer and cancer with T1b and/or Gleason ≥7 were observed in 25% to 50% and 16% to 25% cases, respectively. CONCLUSIONS Older patient age, small prostate volume, and the absence of previous needle biopsy (despite a high PSA level) might be independent risk factors for detecting incidental prostate cancer, although external validation is warranted to confirm our results.