Impact of low and high body mass index on predicting therapeutic efficacy and prognosis in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

OBJECTIVE: To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). METHODS: The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. RESULTS: The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p = 0.002 and p = 0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. CONCLUSION: We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.

Recurrence- and progression-free survival in intermediate-risk non-muscle-invasive bladder cancer: the impact of conditional evaluation and subclassification.

OBJECTIVES: To assess the change in rates of recurrence-free survival (RFS) and progression-free survival (PFS) based on the duration of survival without recurrence or progression among patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), and to examine the predictive factors for recurrence at different time points by assessing conditional RFS and PFS. PARTICIPANTS AND METHODS: A cohort of 602 patients treated with transurethral resection of bladder tumour and histopathologically diagnosed with IR NMIBC was included in this retrospective study. RESULTS: The conditional RFS rate at 1, 2, 3, 4 and 5 years improved with increased duration of RFS; however, the conditional PFS rate did not improve over time. Multivariable analyses showed that recurrent tumour, multiple tumours, tumour size (>3 cm), immediate postoperative instillation of chemotherapy, and administration of BCG were independent predictive factors for recurrence at baseline. The predictive ability of these factors disappeared with increasing recurrence-free survivorship. Subclassification of these patients with IR NMIBC into three groups using clinicopathological factors (recurrent tumour, multiple tumours, tumour size) demonstrated that the high IR group (two factors) had significantly worse RFS than the intermediate (one factor, P < 0.001) and low IR groups (no factor, P = 0.005) at baseline. This subclassification stratified conditional risk of RFS also at 1, 3 and 5 years, which provides the basis for distinct surveillance protocols among patients with IR NMIBC. CONCLUSION: Conditional survival analyses of patients with IR NMIBC demonstrate that RFS changes over time, while PFS does not change. These data support distinct surveillance protocols based on the subclassification of IR NMIBC.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

The risk factors of urinary tract infection after transurethral resection of bladder tumors.

PURPOSE: Few studies mention the necessity of antimicrobial prophylaxis (AMP) for transurethral resection of bladder tumor (TURBT) and the risk factors for postoperative urinary tract infections (UTIs) after TURBT. To evaluate the necessity of AMP and to detect the risk of UTIs, we examined the perioperative clinical factors. METHODS: 687 patients who underwent TURBT between 2006 and 2017 at Hiroshima Prefectural Hospital were examined retrospectively. We defined the postoperative UTIs as febrile UTIs (≥ 38 °C). The AMP for the TURBT that we used was mostly cephalosporin generation 1. The association between the perioperative clinical/pathological factors and postoperative UTIs was assessed by logistic regression retrospectively. RESULTS: 21 patients (3.1%) suffered from postoperative UTIs, and almost all of them were successfully treated with the immediate administration of antibiotics. Univariate analysis showed that past pelvic radiotherapy (p = 0.024, odds ratio (OR) 6.00), tumor size (≥ 2cm) (p = 0.008, OR 3.38), age (≥ 75 years) (p = 0.036, OR 2.65), preoperative hospital stay (≥ 5 days) (p = 0.017, OR 3.76), asymptomatic pyuria (p = 0.038, OR 2.54) and bacteriuria (p = 0.044, OR 2.97) were all associated with postoperative UTIs. CONCLUSIONS: We demonstrated that AMP was effective for patients who underwent TURBT, and history of pelvic radiotherapy, high age, preoperative hospital stay and a certain tumor size were the risk factors as well as pyuria and bacteriuria of postoperative UTIs.

Diagnosis and treatment of benign prostatic hyperplasia in the elderly.

Elderly people are at a high risk of experiencing problems with drug therapy due to age- related changes in the body, as well as exposure to many medications owing to multiple health problems. Medication-related adverse events are common amongst the elderly. Pharmacotherapy for benign prostatic hyperplasia or overactive bladder can generally im- prove lower urinary tract symptoms, whilst also improving the quality of life. However,;these drugs also have the potential to cause dangerous adverse events. For this reason, a great deal of caution should be taken when prescribing medication for elderly patients who are suffer- ing from lower urinary tract symptoms.

[Primary Squamous Cell Carcinoma of the Prostate in which Docetaxel Therapy was Effective : A Case Report].

The patient was a 73-year-old man who visited our hospital with asymptomatic gross hematuria. Cystoscopy revealed a bladder tumor in two places. Serum prostatic specific antigen was normal (2.535 ng/ml). Transurethral resection of bladder tumors was performed. In order to complete resection of bladder tumor, transurethral resection of right lobe of the prostate whitch had protruded into the bladder, was needed. Histology of the prostatic tissue revealed squamous cell carcinoma with no grandular and acinar structures. Serum SCC-antigen level was evaluated (6.2 ng/ml) after establishment of the diagnosis. Thoraco-abdominal computed tomography and 18-fluorodeoxyglucose positron emission tomography/ computed tomography ((18)F-FDG PET/CT) showed prostate cancer and multiple metastases in the lymph nodes, such as right external iliac, right common iliac, para-aortic and left supraclavicular region. The patient received external radiation therapy to the prostate and underwent systemic chemotherapy using docetaxel. After 2 courses of docetaxel therapy, multiple lymph nodes metastases were reduced and serum SCC-antigen level was normalized. Docetaxel therapy could not be continued because of a side effect of interstitial pneumonia.

Rat cavernous nerve reconstruction with CD133+ cells derived from human bone marrow.

INTRODUCTION: Erectile dysfunction remains a major complication after surgery of pelvic organs, especially after radical prostatectomy. AIM: The aim of this study was to assess the effect of endothelial progenitor cells on the regeneration of cavernous nerves in a rat injury model. METHODS: A 2 mm length of the right and left cavernous nerves of 8-week-old male nude rats were excised. Alginate gel sponge sheets supplemented with 1 × 10(4) CD133+ cells derived from human bone marrow were then placed over the gaps on both sides (CD group). The same experiments were performed on sham-operated rats (SH group), rats with only the nerve excision (EX group), and rats with alginate gel sheets placed on the injured nerves (AL group). MAIN OUTCOME MEASURES: Immunofluorescence staining and molecular evaluation were performed 4 days later. Functional and histological evaluations were performed 12 weeks later. RESULTS: The intracavernous pressure elicited by electrical stimulation and the neuronal nitric oxide synthase-positive area in surrounding tissues of the prostate was significantly greater in the CD group. Immunofluorescence microscopy showed that CD133+ cells were assimilated as vascular endothelial cells, and the real-time polymerase chain reaction showed upregulation of nerve growth factor and vascular endothelial growth factor in the alginate gel sponge sheets of the CD group. CONCLUSIONS: Transplantation of CD133+ cells accelerated the functional and histological recovery in this cavernous nerve injury model, and the recovery mechanism is thought to be angiogenesis and upregulation of growth factors. CD133+ cells could be an optional treatment for cavernous nerve injury after prostatectomy in clinical settings.

Therapeutic efficacy of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome.

OBJECTIVES: Narrow band imaging cystoscopy can increase the visualization and detection of Hunner's lesions. A single-center, prospective clinical trial was carried out aiming to show the effectiveness of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome. METHODS: A total of 23 patients (19 women and 4 men) diagnosed as having ulcer-type interstitial cystitis/painful bladder syndrome were included. All typical Hunner's lesions and suspected areas identified by narrow band imaging were electrocoagulated endoscopically after the biopsy of those lesions. Therapeutic efficacy was assessed prospectively by using visual analog scale score of pain, O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score. RESULTS: The mean follow-up period was 22 months. All patients (100%) experienced a substantial improvement in pain. The average visual analog scale pain scores significantly decreased from 7.3 preoperatively to 1.2 1 month postoperatively. A total of 21 patients (91.3%) who reported improvement had at least a 50% reduction in bladder pain, and five reported complete resolution. Daytime frequency was significantly decreased postoperatively. O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score were significantly decreased postoperatively. However, during the follow-up period, a total of six patients had recurrence, and repeat narrow band imaging-assisted transurethral electrocoagulation of the recurrent lesions was carried out for five of the six patients, with good response in relieving bladder pain. CONCLUSIONS: Our results showed that narrow band imaging-assisted transurethral electrocoagulation could be a valuable therapeutic alternative in patients with ulcer-type interstitial cystitis/painful bladder syndrome, with good efficacy and reduction of recurrence rate.

Significance of timing of therapeutic line on effectiveness of nivolumab for metastatic renal cell carcinoma.

Objectives: This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma. Marterials and methods: Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied. Patients who were treated with nivolumab as second-line therapy were included in the second-line group, while the others were included in the later-line group. The clinicopathological characteristics, effects of nivolumab, and prognoses of these groups were compared. Results: Twenty and thirty-eight patients were included in the second-line and later-line groups, respectively. There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups. The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group (15% vs. 50%, p = 0.0090). The 50% progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group (not reached and 5 months, p = 0.0018). Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival (p = 0.0028, hazard ratio = 0.108). The 50% overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months, respectively (p = 0.2652). Conclusions: The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

Comparison of renal function after partial nephrectomy and radical nephrectomy for renal cell carcinoma.

OBJECTIVE: To investigate the time-dependent changes of estimated glomerular filtration rate (eGFR) after radical nephrectomy (RN) and partial nephrectomy (PN) for renal cell carcinoma (RCC) and to determine the risk factors for the new onset of a postoperative eGFR <60 ml/min/1.73 m(2). PATIENTS AND METHODS: We assessed the renal function of 253 RCC patients by using the eGFR, and investigated the time-dependent changes of the eGFR after the operation. Regression models were used to determine risk factors for the new onset of an eGFR of <60 ml/min/1.73 m(2) in 211 patients who had at least one month of postoperative follow-up. RESULTS: From the first postoperative day to the 60th postoperative month the eGFR in the RN group was significantly lower than that in the PN group. For patients who had at least 1 month of postoperative follow-up, multivariable analysis revealed that RN (p < 0.001), age (p = 0.028), and maleness (p = 0.013) were risk factors for the postoperative onset of an eGFR <60 ml/min/1.73 m(2). CONCLUSIONS: Renal function after PN was better than that after RN, and RN was a greater risk factor for the postoperative onset of an eGFR <60 ml/min/ 1.73 m(2).

Impact of pre-implant lower urinary tract symptoms on postoperative urinary morbidity after permanent prostate brachytherapy.

OBJECTIVES: To assess the impact of baseline lower urinary tract symptoms on postoperative urinary morbidity in patients being treated for prostate cancer with 125-I permanent prostate brachytherapy. METHODS: A total of 104 prostate cancer patients were enrolled in this study. Their urinary morbidity was followed up using the International Prostate Symptom Score and Expanded Prostate Cancer Index Composite for 12 months or more after permanent prostate brachytherapy. Patients were classified into two groups based on their baseline International Prostate Symptom Score: the low International Prostate Symptom Score group (score ≤ 7) and the high International Prostate Symptom Score group (score ≥ 8). Urinary morbidity was estimated in each group based on the results of the International Prostate Symptom Score and Expanded Prostate Cancer Index Composite measured before permanent prostate brachytherapy, and at 1, 3, 6, 9 and 12 months after the end of all radiation therapy. RESULTS: The overall mean total International Prostate Symptom Score, International Prostate Symptom Score quality of life score, and urinary-related scores for Expanded Prostate Cancer Index Composite were significantly worse at 1 month after the end of treatment, but they improved gradually after the treatment and recovered to the baseline level within 12 months. Even in the high-International Prostate Symptom Score group, the International Prostate Symptom Score and International Prostate Symptom Score Quality of Life score were significantly worse at 1-3 months after permanent prostate brachytherapy, and then recovered to the baseline level without prolongation. Although the urination-related Expanded Prostate Cancer Index Composite score in the high-International Prostate Symptom Score group was significantly worse at 1 month after permanent prostate brachytherapy in comparison with that in the low-International Prostate Symptom Score group, it recovered to the baseline level without prolongation. CONCLUSIONS: The present findings suggest that the presence of lower urinary tract symptoms before implantation does not prolong urinary morbidity after permanent prostate brachytherapy.

Histological variants and lymphovascular invasion in upper tract urothelial carcinoma can stratify prognosis after radical nephroureterectomy.

OBJECTIVES: Patients with histological variants (HV) of bladder cancer have more advanced disease and poorer survival rates than those with pure urothelial carcinoma (UC). Moreover, lymphovascular invasion (LVI) is an important biomarker after RNU in systematic reviews and meta-analyses. Thus, here we investigated the clinical and prognostic impact of HV and LVI in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: Data from 223 UTUC patients treated with RNU without neoadjuvant chemotherapy were retrospectively evaluated. We analyzed differences in clinicopathological features and survival rates between patients with pure UC and those with HV. Conditional survival (CS) analysis was performed to obtain prognostic information over time. RESULTS: A total of 32 patients (14.3%) had HV, with the most common variant being squamous differentiation, followed by glandular differentiation. UTUC with HV was significantly associated with advanced pathological T stage (pT ≥ 3), higher tumor grade (G3), and LVI, compared to pure UC (all P < 0.01). Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were all significantly worse in the HV group compared to the pure UC group (all, P < 0.001). In multivariable analysis, HV and LVI were independent predictors of CSS and OS. We classified the patients into three groups using these two predictors: low-risk (neither HV nor LVI), intermediate-risk (either HV or LVI), and high-risk (both HV and LVI). Significant differences in PFS, CSS, and OS rates were found among the 3 groups. In CS analysis, the conditional PFS, CSS, and OS rates at 1, 2, 3, 4, and 5 years improved with increased duration of event-free survival. CS analysis revealed that most progression events occurred within 2 years after RNU, and patients with risk factors had worse PFS at all time points. CONCLUSIONS: A risk model using HV and LVI can stratify PFS, CSS, and OS of patients treated with RNU. In addition, CS analysis revealed that HV and LVI were poor prognostic factors over time after RNU.

Impact of modified Glasgow prognostic score on predicting prognosis and modification of risk model for patients with metastatic renal cell carcinoma treated with first line tyrosine kinase inhibitor.

INTRODUCTION AND OBJECTIVES: Intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria is thought to consist of patients with different prognoses. This study investigated the impact of a pretreated modified Glasgow prognostic score (mGPS), which is defined on the basis of the pretreated serum albumin and C-reactive protein level, on predicting the prognosis of patients with metastatic renal cell carcinoma (mRCC) and its usefulness for the re-stratification of patients into a more improved risk model. MATERIALS AND METHODS: One hundred ninety-six mRCC patients treated with first-line tyrosine kinase inhibitor (TKI) were retrospectively investigated. All patients were classified into either a high-mGPS or a low-mGPS group on the basis of mGPS score upon starting systemic therapy, the overall survival (OS) and cancer specific survival (CSS) rates in each group were compared. We use decision curve analysis and calculate C-index based on OS and CSS to compare IMDC+mGPS model and IMDC model. RESULTS: The categories of favorable, intermediate, and poor risk groups in the IMDC model were assessed in 32, 113, and 51 cases, respectively. The low- and high-mGPS groups consisted of 149 and 47 cases. The median OS in the high- and low-mGPS groups were 38.4 months and 5.6 months, and their median CSSs were 41.0 months and 5.6 months, respectively (P < 0.0001). Multivariate analysis showed that a high mGPS, multiple metastatic organs, and hypercalcemia were independent predictive factors for a worse OS (P = 0.0260). Next, we divided the intermediate risk group into two subgroups using the mGPS score. The OS and CSS for the high-mGPS subgroup were significantly worse than those for the low-mGPS one (P = 0.0024, median OS: 21.0 months and 33.7 months, P = 0.0007, median CSS: 21.0 months and 39.8 months), and there was no significant difference in OS between the high-mGPS subgroup in the intermediate risk group and poor risk group (P = 0.2250). The value of C-index based on OS at IMDC and IMDC+mGPS model were 0.6771 and 0.6967, and those based on CSS were 0.6850 and 0.7080, respectively. In decision curve analysis to evaluate the clinical net benefit using the IMDC+mGPS model compared to the IMDC model, there was no significant difference between the two groups. CONCLUSION: mGPS is useful for establishing a more improved prognostic model that is able to stratify mRCC patients treated with first-line TKI.

Prognostic model of upfront cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors and/or targeted agents.

INTRODUCTION AND OBJECTIVES: The aim of this study was to investigate prognostic factors and to establish a prognostic model using them for upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI) and/or tyrosine kinase inhibitor (TKI). MATERIALS AND METHODS: Two hundred eleven patients who were diagnosed as mRCC at initial diagnosis and were treated with TKI and/or ICI were classified into 2 groups: those undergoing CN (upfront CN group, 117 cases) and those who initially underwent systemic therapy (non-upfront CN group, 94 cases). In the upfront CN group, the patients' background and overall survival (OS) were compared with those in the other two groups, and prognostic factors were analyzed. A prognostic model of the upfront CN group was established. RESULTS: The median of the observation period for the upfront CN group was 25 months. The rates of patients with clear cell histology, with a Karnofsky performance status (KPS) of ≥ 80%, with a single metastatic organ, with a normal pretreated C-reactive protein level, and with an intermediate risk according to the International mRCC Database Consortium (IMDC) model were significantly higher than those in the non-upfront CN group (87.2% and 30.9%, p < 0.0001; 92.3% and 77.7%, p = 0.0025; 41.9% and 24.5%, p = 0.0080; 47.9% and 13.8%, p < 0.0001; 66.7% and 45.7%, p = 0.0023, respectively). The 50% OS in the upfront CN group was 33.1 months, significantly better than that in the non-upfront CN group (11.1 months, p < 0.0001), and these results were consistent regardless of their prognostic risk level. Multivariate analysis showed that multiple metastatic organs and a KPS of < 80% were independent predictive factors for OS (hazard ratio: 1.653 and 2.995, p = 0.0339 and 0.0054, respectively). Using these two parameters to stratify the upfront CN group, the 50% OSs in cases with no risk factors, in those with one factor, and in those with two factors were 43.4 months, 29.1 months, and 7.7 months, respectively (p < 0.0001). CONCLUSION: The upfront CN group was able to be stratified by our prognostic model into three subgroups with different prognoses. This model can provide useful information for making decisions in consideration of upfront CN in patients with mRCC.

Six-year experience of permanent prostate brachytherapy for clinically localized prostate cancer.

This report presents the outcome of prostate permanent brachytherapy (PPB). One hundred and seventy-two patients with clinically localized prostate cancer were treated with permanent brachytherapy using iodine-125 seeds (125-I) at Hiroshima University Hospital from July 2004 to June 2010. This study evaluated the efficacy of PPB in these patients. The median patient age was 69 years (range 53 to 82 years), the median prostate-specific antigen (PSA) value before biopsy was 6.75 ng/ml (range 3.5 to 47.9 ng/ml), and the median prostate volume was 23.1 ml (range 10.1 to 57 ml). The median follow-up was 37 months (range 1 to 72 months). The serum PSA levels decreased continuously after PPB throughout the entire follow-up period in 97% of patients without neoadjuvant hormonal therapy. No relapse occurred during the follow-up period in patients at low risk. Our 6-year experience suggests that PPB is effective for localized prostate cancer. Patients with prostate cancer that does not require combined external beam radiation therapy (EBRT) have the best chance of responding to treatment.

Hydrogel spacer shrinkage during external-beam radiation therapy following low-dose-rate brachytherapy for high-risk prostate cancer: a case series.

BACKGROUND: Few studies have assessed hydrogel spacer shrinkage during external-beam radiation therapy following brachytherapy for localized high-risk prostate cancer. This case presentation evaluated the changes in hydrogel spacer appearance by magnetic resonance imaging during external-beam radiation therapy after brachytherapy for prostate cancer and analyzed the effect of this shrinkage on the dose distribution in four cases. CASE PRESENTATION: In all cases, we implanted 125I sources using a modified peripheral loading pattern for seed placement. The prescribed dose for each implant was 110 Gy. After delivering the sources, a hydrogel spacer was injected. All cases underwent external-beam radiation therapy approximately 1-2 months after brachytherapy. The prescribed dose of external-beam radiation therapy was 45 Gy in 1.8-Gy fractions. Magnetic resonance imaging was performed for evaluation on the day following seed implantation (baseline), at external-beam radiation therapy planning, and during external-beam radiation therapy. The median hydrogel spacer volume was 16.2 (range 10.9-17.7) cc at baseline, 14.4 (range, 9.4-16.1) cc at external-beam radiation therapy planning, and 7.1 (range, 2.0-11.4) cc during external-beam radiation therapy. The hydrogel spacer volume during external-beam radiation therapy was significantly lower than that at external-beam radiation therapy planning. The rectum V60-80 (rectal volume receiving at least 60-80% of the prescribed dose of external-beam radiation therapy) during external-beam radiation therapy was significantly higher than that at external-beam radiation therapy planning. CONCLUSIONS: The potential reduction in hydrogel spacer size during external-beam radiation therapy following brachytherapy can lead to unexpected irradiation to the rectum. This case presentation would be helpful for similar cases.

Erratum: Improved prognosis for elderly patients with metastatic renal cell carcinoma in the era of targeted therapy.

[This corrects the article DOI: 10.3892/mco.2020.2020.].

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor.

BACKGROUND: There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI. MATERIALS AND METHODS: A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed. RESULTS: Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively. CONCLUSIONS: Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.

The Impact of Histological Variant on Oncological Outcomes in Patients With Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy.

BACKGROUND/AIM: Bladder cancer with histological variant (HV) has different morphological features from usual urothelial carcinoma (UC). The aim of this study was to evaluate the oncological outcomes of HV in patients with bladder cancer. PATIENTS AND METHODS: We retrospectively evaluated data from 102 patients with UC of the bladder treated with radical cystectomy between 1998 and 2017. Pathological findings including HV were assigned by one dedicated pathologist. Recurrence-free survival (RFS) and cancer-specific survival (CSS) and overall survival (OS) were estimated by Cox regression models. RESULTS: In total, 26 patients (25.5%) had HV, and the most common variant was squamous differentiation, followed by glandular differentiation and a mixed variant consisted of squamous and glandular differentiation. The presence of HV was associated with RFS and CSS (p=0.018, p=0.036, respectively). CONCLUSION: HV has more aggressive tumor biological features compared to those with pure UC. The presence of HV was associated with poor survival.

Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer.

PURPOSE: There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA. METHODS: Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed. RESULTS: Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy. CONCLUSIONS: Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.