Renal function outcome after selective bladder-preserving tetramodality therapy consisting of maximal transurethral resection, induction chemoradiotherapy and consolidative partial cystectomy in comparison with radical cystectomy for patients with muscle-invasive bladder cancer: a two-centre retrospective study.

OBJECTIVE: To compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC). METHODS: This study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed. RESULTS: The number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of -0.7 and -1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC. CONCLUSIONS: RF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.

External validation of the Briganti 2019 nomogram to identify candidates for extended pelvic lymph node dissection among patients with high-risk clinically localized prostate cancer.

BACKGROUND: We aimed to establish an external validation of the Briganti 2019 nomogram in a Japanese cohort to preoperatively evaluate the probability of lymph node invasion in patients with high-risk, clinically localized prostate cancer. METHODS: The cohort consisted of 278 patients with prostate cancer diagnosed using magnetic resonance imaging-targeted biopsy who underwent radical prostatectomy and extended pelvic lymph node dissection from 2012 to 2020. Patients were rated using the Briganti 2019 nomogram, which evaluates the probability of lymph node invasion. We used the area under curve of the receiver operating characteristic analysis to quantify the accuracy of the nomogram. RESULTS: Nineteen (6.8%) patients had lymph node invasion. The median number of lymph nodes removed was 18. The area under the curve for the Briganti 2019 was 0.71. When the cutoff was set at 7%, 84 (30.2%) patients with extended pelvic lymph node dissection could be omitted, and only 1 (1.2%) patient with lymph node invasion would be missed. Sensitivity, specificity, and negative predictive values at the 7% cutoff were 94.7, 32.0, and 98.8%, respectively. CONCLUSION: This external validation showed that the Briganti 2019 nomogram was accurate, although there may still be scope for individual adjustments.

First-line combination chemotherapy with etoposide, ifosfamide and cisplatin for the treatment of disseminated germ cell cancer: Efficacy and feasibility in current clinical practice.

OBJECTIVES: To evaluate the efficacy and safety profiles of first-line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first-line chemotherapy for disseminated germ cell cancer. METHODS: This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first-line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short-acting granulocyte colony-stimulating factor (non-primary prophylaxis group). RESULTS: The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post-chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non-primary prophylaxis groups (100% vs 90%, P < 0.01). The 5-year salvage treatment-free and overall survival rates were 83% and 94%, respectively. In total, 138 patients (90%) developed grade 4 hematological toxicities, and there were no treatment-related deaths due to myelosuppression. Grade 4 neutropenia was less commonly observed in the primary prophylaxis group compared with the non-primary prophylaxis group (80% vs 95%, P < 0.01). CONCLUSIONS: This is the largest study of first-line etoposide, ifosfamide and cisplatin, and its sufficient efficacy and safety profiles are confirmed in current clinical practice. Primary prophylaxis using pegfilgrastim might further improve the feasibility of etoposide, ifosfamide and cisplatin.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Intraoperative Only versus Extended Duration Use of Antimicrobial Prophylaxis for Infectious Complications in Radical Cystectomy with Intestinal Urinary Diversion.

INTRODUCTION: In spite of the high incidence of infectious complications (ICs), appropriate duration of antimicrobial prophylaxis (AMP) for radical cystectomy (RC) with intestinal urinary diversion (IUD) has not been established. We compared the incidence of ICs after RC with IUD in patients using only intraoperative AMP or extended duration AMP. Risk factors for ICs were also investigated. PATIENTS AND METHODS: One hundred twenty-three consecutive patients who underwent RC with IUD were divided into 2 groups based on the AMP duration (intraoperative only vs. extended duration for a median of 3 days). Between the groups, the incidence of ICs was compared. Risk factors for ICs were investigated in multivariate analysis. RESULTS: The IC rate was 44%. No significant difference was found in the rate of ICs between the groups. The IC rate was significantly higher in patients with lower estimated glomerular filtration rate (eGFR). Rates of ICs were 60 and 38% in patients with eGFR of less than 60 and equal or more than 60 mL/min/1.73 m2, respectively. CONCLUSIONS: Our result indicates that AMP that is administered more than intraoperatively may be excessive in RC with IUD. Patients with a lower eGFR should be particularly cared for postoperative ICs.

Incidence and Predictors of Deep Vein Thrombosis in Patients with Elevated Serum D-Dimer Prior to Surgery for Urologic Malignancy.

OBJECTIVES: To analyze the incidence and predictors of deep vein thrombosis (DVT) in patients with elevated D-dimer prior to surgery for urologic malignancy. METHODS: Between January 2015 and September 2017, 987 consecutive patients underwent surgery for urologic malignancy under general anesthesia in our institution. Of these, 191 patients underwent preoperative venous ultrasonography of the lower extremities for DVT due to elevated D-dimer. We analyzed the incidence and predictors of DVT in these patients. RESULTS: The median age was 69 years. DVT was detected in 18% of patients (35/191). Multivariate analysis showed that the primary site of urologic malignancy (p < 0.01) and older age (p < 0.01) were independent predictors of DVT. Patients with bladder cancer had the highest incidence of DVT. When bladder cancer and age of 70 or older were defined as predictors for DVT, the incidence of DVT in zero, 1, and 2 predictors was 3.4% (3/89), 29% (22/77), and 44% (11/25), respectively. CONCLUSIONS: DVT was found in 18% of patients with elevated D-dimer prior to surgery for urologic malignancy. Bladder cancer patients and older patients in whom D-dimer has been elevated should undergo careful early examination for DVT.

Improvement of renal function by changing the bone-modifying agent from zoledronic acid to denosumab.

BACKGROUND: In order to help in selecting the optimum bone-modifying agent (BMA; zoledronic acid or denosumab), we investigated the impact of the BMA on the renal function of patients with bone metastases. MATERIALS AND METHODS: The present study consisted of 118 patients who were treated with denosumab for bone metastases secondary to prostate cancer, renal cell cancer, and urothelial cancer at our hospital between 2012 and 2015. The clinical course of the renal function of these patients, treated with zoledronic acid or denosumab, was retrospectively evaluated. RESULTS: Of the 118 patients who were treated with denosumab during the study period, 57 (48 %) had previously been administered zoledronic acid and 61 (52 %) had received denosumab as the first-line BMA. The reasons for changing from zoledronic acid to denosumab were increased creatinine serum level (26 patients, 46 %), patient preference (16 patients, 28 %), difficulty with venous infusion (10 patients, 17 %), and other reasons (5 patients, 9 %). The median level of creatinine clearance in the patients who changed from zoledronic acid to denosumab due to increased serum creatinine level was 59.9 ml/min before administration of zoledronic acid, 40.9 ml/min at the beginning of denosumab treatment, 47.5 ml/min at 3 months after administration of denosumab, and 52.0 ml/min at the last follow-up. There were significant differences. CONCLUSIONS: For the first time, we demonstrated that the renal function of some patients, which had deteriorated following zoledronic acid administration, successfully improved after changing to denosumab.

Clinical outcome of urachal cancer in Japanese patients.

BACKGROUND: The outcome of treatment of Japanese patients with urachal cancer is not well known. The purpose of this study is to clarify the characteristics and outcomes of Japanese patients with urachal cancer. MATERIALS AND METHODS: The medical records of patients with urachal cancer who were treated in our hospital between 1994 and 2014 were retrospectively reviewed and statistically analyzed. RESULTS: We found 28 patients who had been diagnosed with urachal cancer and treated in our hospital during the study period. The median age of these patients was 52.3 years [interquartile range (IQR), 46.0-56.8 years]. Seventeen patients underwent surgery in our department. The median observation period of these patients was 42.6 months (IQR, 21.1-49.7 months). Among patients who had undergone surgery, cancer recurred in 7 (41 %). The estimated median time from surgery to recurrence and overall survival (OS) period were 35.8 months [95 % confidence interval (CI), 7.7 months-not determined] and not reached, respectively. Seventeen patients received chemotherapy for metastatic disease. The estimated median OS time from initial metastasis was 23.5 months (95 % CI, 11.8-33.3 months). CONCLUSIONS: Urachal cancer is usually locally advanced at presentation and it has a high risk of distant metastases. However, long-term survival following surgical treatment occurs in a significant fraction of patients. This study indicates the current treatment results for patients with urachal cancer in Japanese clinical practice. To establish a standard operation method and chemotherapy, a multicenter, prospective study is needed in a larger population in the future.

Clinical Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Upper Tract Urothelial Carcinoma: Impact on Detection of Metastases and Patient Management.

OBJECTIVE: To determine the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis and its impact on patient management with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Consecutive patients with UTUC underwent 18F-FDG PET/CT after CT for initial staging (n = 47) and for restaging at recurrence (n = 9). Diagnostic accuracy for detecting metastases with PET/CT and CT was compared statistically. The impact of PET/CT on patient management was assessed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. RESULTS: In the lesion-based analysis, 142 lesions were diagnosed as metastases. The sensitivity of PET/CT was significantly better than that of CT (85 vs. 50%, p = 0.0001). In the patient-based analysis, 22 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy of PET/CT tended to be superior to those of CT, but these values were not significantly different (95, 91, and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, and 0.063, respectively). The clinicians changed their assessments of disease extent and management plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. CONCLUSIONS: The diagnostic accuracy of PET/CT for detecting metastasis was superior to that of CT. PET/CT provided additional information to the CT-based staging, which had an impact on patient management.

Clinical outcome of patients with pancreatic metastases from renal cell cancer.

BACKGROUND: Renal cell cancer (RCC) is one of the most frequent primary sites for metastatic pancreatic tumors although metastatic tumors are rare among pancreatic malignant tumors. The purpose of this study is to disclose the characterization and treatment outcomes of pancreatic metastases from RCC. METHODS: Of 262 patients with metastatic RCC treated at our hospital between 1999 and 2013, the data of 20 (7.6%) who simultaneously developed or subsequently acquired pancreatic metastases were retrospectively reviewed and statistically analyzed. RESULTS: The median follow-up period from RCC diagnosis and pancreatic metastases was 13.4 years (inter-quartile range: IQR, 7.8-15.5 years) and 3.8 years (IQR, 2.1-5.5 years), respectively. Median duration from diagnosis of RCC to pancreatic metastasis was 7.8 years (IQR, 4.2-12.7 years). During this observation period, the estimated median overall survival (OS) time from the diagnosis of RCC to death or from pancreatic metastasis to death was not reached. The probability of patients surviving after pancreatic metastasis at 1, 3, and 5 years was 100, 87.7, and 78.9%, respectively. The estimated OS period from the diagnosis of metastases to death of the patients with pancreatic metastasis was significantly longer than that of the patients with non-pancreatic metastasis (median OS 2.7 years) (P < 0.0001). Surgical management for pancreatic metastasis was performed in 15 patients (75%). When the median follow-up period for these surgeries was 3.5 years (IQR, 1.9-5.2 years), the estimated median recurrence-free survival was 1.8 years. For the patients with multiple metastatic sites, molecularly targeted therapies were given to six (30%) patients. When the median follow-up period was 4.1 years (IQR, 3.0-4.4 years), no disease progression was observed. CONCLUSIONS: The pancreas is frequently the only metastatic site and metastasis typically occurs a long time after nephrectomy. The OS period of these patients is long and both surgical and medical treatment resulted in good outcomes.

Diagnostic performance and safety of a three-dimensional 14-core systematic biopsy method.

OBJECTIVE: To investigate the diagnostic performance and safety of a three-dimensional 14-core biopsy (3D14PBx) method, which is a combination of the transrectal six-core and transperineal eight-core biopsy methods. PATIENTS AND METHODS: Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our institutions and were analysed prospectively. Biopsy criteria included a PSA level of 2.5-20 ng/mL or abnormal digital rectal examination (DRE) findings, or both. The primary endpoint of the study was diagnostic performance and the secondary endpoint was safety. We applied recursive partitioning to the entire study cohort to delineate the unique contribution of each sampling site to overall and clinically significant cancer detection. RESULTS: Prostate cancer was detected in 503 of the 1103 patients (45.6%). Age, family history of prostate cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with the positive biopsy results significantly and independently. Of the 503 cancers detected, 39 (7.8%) were clinically locally advanced (≥cT3a), 348 (69%) had a biopsy Gleason score (GS) of ≥7, and 463 (92%) met the definition of biopsy-based significant cancer. Recursive partitioning analysis showed that each sampling site contributed uniquely to both the overall and the biopsy-based significant cancer detection rate of the 3D14PBx method. The overall cancer-positive rate of each sampling site ranged from 14.5% in the transrectal far lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210 patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found to have pathologically non-organ-confined disease, 174 (83%) had prostatectomy GS ≥7 and 185 (88%) met the definition of prostatectomy-based significant cancer. CONCLUSIONS: This is the first prospective analysis of the diagnostic performance of an extended biopsy method, which is a simplified version of the somewhat redundant super-extended three-dimensional 26-core biopsy. As expected, each sampling site uniquely contributed not only to overall cancer detection, but also to significant cancer detection. 3D14PBx is a feasible systematic biopsy method in men with PSA <20 ng/mL.

Surveillance policy for Japanese patients with stage I testicular germ cell cancer in the multi-detector computed tomography era.

BACKGROUND: The outcome of surveillance for Japanese patients with clinical stage I testicular germ cell cancer (GCC) was investigated in the multi-detector computed tomography (MDCT) era. METHODS: The medical records of 92 Japanese patients with stage I GCC, who received treatment in our institution between March 1999 and February 2013, were reviewed. As six patients requested and received prophylactic chemotherapy and two patients seriously deviated from surveillance schedule, these patients were excluded from the study. Data from a total 84 patients were analyzed, RESULTS: The median follow-up period following diagnosis was 5.1 years (inter-quartile range: IQR, 2.3-7.7 years). Of the 84 patients, eight (9.5 %) had a recurrence of their cancer in this observation period. Regarding histologic subtypes, the recurrence rates were five (9.3 %) of the 54 patients with seminoma and three (10 %) of the 30 patients with nonseminomatous germ cell tumor (NSGCT). All eight patients who experienced a recurrence did so within 2 years; they all underwent induction chemotherapy and remain alive at the time of writing, with no evidence of disease. Among 31 seminoma patients with a tumor more than 4 cm in size and rete testis invasion, cancer recurred in three (9.7 %) during the surveillance period. On the other hand, among the 13 patients with NSGCT and vascular invasion, three (23 %) experienced a recurrence, whereas the figure was zero for the 11 (0 %) patients without vascular invasion. CONCLUSION: Fewer than 10 % of Japanese patients with stage I testicular GCC suffered a recurrence in the 5-year observation period of this study. The risk of occult disease, which will result in relapse, might be decreased in the MDCT era. All patients must be fully informed of the anticipated recurrence rate and the potential risks of exposure to chemotherapy agents.

Clinical response to induction chemotherapy predicts improved survival outcome in urothelial carcinoma with clinical lymph nodal metastasis treated by consolidative surgery.

BACKGROUND: To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). METHODS: Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). RESULTS: The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. CONCLUSIONS: The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

Phase-1 study of abiraterone acetate in chemotherapy-naïve Japanese patients with castration-resistant prostate cancer.

Persistent androgen synthesis under castration status in adrenal gland, testes and tumor cells is thought to be one of the major causes of development and progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and dose-escalation study. Chemotherapy-naïve Japanese CRPC patients (N = 27) received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28-day treatment cycles. In the first cycle, AA monotherapy was given on days 1-7 for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to 28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18 July 2013). Over the evaluated dose range, plasma abiraterone concentrations increased with dose, with median tmax 2-3 h. At each dose level, mean serum corticosterone concentrations increased, while testosterone and dehydroepiandrosterone sulfate concentrations rapidly decreased following a single AA dose and were further reduced to near the quantification limit on day 8 regardless of the dose. At least 3 patients from each dose-group experienced ≥50% prostate-specific antigen reduction, suggesting clinical benefit from AA in Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This study is registered at ClinicalTrials.gov: NCT01186484.

Successful use of endoscopic argon plasma coagulation for hemorrhagic radiation cystitis: a case report.

Hemorrhagic radiation cystitis is an example of a typical radiotherapy-induced adverse event. However, the optimal treatment for hemorrhagic radiation cystitis is not known. There are limited data regarding the use of argon plasma coagulation for hemorrhagic radiation cystitis. Here, we present the use of argon plasma coagulation using a gastrointestinal endoscope to treat hemorrhagic radiation cystitis. The patient was a 75-year-old male patient with hemorrhagic radiation cystitis due to external beam irradiation for prostate adenocarcinoma. Six years after radiotherapy, the patient presented with macroscopic hematuria over the preceding 4 months, and laboratory investigations revealed a low hemoglobin level. The hematuria was not controlled with 2 days of bladder irrigation using normal saline. Thus, argon plasma coagulation using an upper gastrointestinal endoscope was considered for treatment of the hemorrhagic radiation cystitis. The cystoscopic examination revealed diffuse radiation cystitis with oozing telangiectasia and coagula. All of the bleeding sites and telangiectasia were coagulated using argon plasma coagulation. Following treatment, the patient's clinical symptoms improved and did not recur. The hemoglobin level also recovered. No complications associated with the treatment were observed during the 6-month follow-up period. Thus, argon plasma coagulation using a gastrointestinal endoscope is a safe and effective treatment for hemorrhagic radiation cystitis.

Longitudinal change in health-related quality of life after intensity-modulated radiation monotherapy for clinically localized prostate cancer.

PURPOSE: The purpose of the study is to assess longitudinal changes in general and disease-specific health-related quality-of-life (HRQOL) indices after intensity-modulated radiotherapy (IMRT) monotherapy for patients with localized prostate cancer (PCA). METHODS: Between 2006 and 2010, 91 patients with localized PCA underwent IMRT monotherapy and were enrolled into this prospective study. At baseline, and at 3, 6, 12, and 24 months after IMRT, the general and prostate-specific HRQOL were estimated using physical (PCS) and mental component summaries (MCS) calculated using the Medical Outcomes Study 8-Item Short Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC). RESULTS: For 2 years, there were no significant changes in EPIC scores in all subscales of urinary domain, hormonal function, and bother. Bowel and sexual function scores decreased after IMRT and did not return to those at baseline (p = 0.006 and < 0.001, respectively). PCS began to decrease at 3 months after IMRT and then returned to the baseline score at 24 months. In contrast, the MCS score began to significantly increase after IMRT, and thereafter the score remained constant until 24 months (p < 0.001). On multivariate logistic regression analysis, urinary (p = 0.003) and sexual functions (p = 0.0005) at baseline were identified as significant predictors of EPIC urinary irritative/obstructive score and sexual function at 24 months after IMRT. CONCLUSION: Urinary function, including irritative/obstruction symptoms and hormonal function, was not affected by IMRT. However, bowel and sexual function decreased after IMRT. These findings will provide important information for PCA patients considering IMRT.

Long-term oncological outcome in men with T3 prostate cancer: radical prostatectomy versus external-beam radiation therapy at a single institution.

BACKGROUND: This study was designed to compare the long-term oncological outcome of patients with clinical T3 (cT3) prostate cancer (PCA) treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and to identify predictors of oncological outcomes. METHODS: A total of 231 patients with cT3 PCA underwent either RP (n = 112) or EBRT (n = 119). Local progression-free (LPFS), distant metastasis-free (DMFS), cancer-specific (CSS), and overall survival curves were generated with the Kaplan-Meier method, and the differences in survival rates between the two groups were assessed with a log-rank test. Cox proportional stepwise multivariate analysis was used to assess the association of variables to the oncological outcomes. RESULTS: The median follow-up of the RP and EBRT groups was 93 and 85 months, respectively (p = 0.004).The 10-year LPFS, DMFS, and CSS rates were not statistically different between the two groups (90.2, 73.9, and 93.7 % in the RP group and 82.7, 88.2, and 85.1 % in the EBRT group; p = 0.25, 0.10, and 0.10, respectively). The Cox proportional multivariate analysis revealed that clinical T3b (cT3b) (p = 0.001) and a biopsy Gleason score of 7-10 (p = 0.043) were significant predictors of cancer-specific mortality and that cT3b was also a significant predictor of local progression and all-cause mortality. CONCLUSION: In cT3 PCA, both RP and EBRT provide an excellent long-term oncological outcome. cT3b was the strongest predictor of oncological outcome for the patients with locally advanced PCA who underwent the definitive therapy.

First-line combination chemotherapy with cisplatin, etoposide and ifosfamide for the treatment of disseminated germ cell cancer: re-evaluation in the granulocyte colony-stimulating factor era.

BACKGROUND: This study re-evaluated the efficacy and tolerability of cisplatin, etoposide, and ifosfamide (VIP) combination chemotherapy as an alternative first-line regimen for patients with disseminated germ cell cancer (GCC) in this granulocyte colony-stimulating factor (G-CSF) era. METHODS: The medical records of 91 consecutive patients with previously untreated disseminated GCC who received first-line VIP between 1995 and 2011 were retrospectively reviewed. RESULTS: The 5-year overall survival rates for patients with good (n = 49), intermediate (n = 22) and poor (n = 20) prognoses according to the International Germ Cell Cancer Collaborative Group classification were 100, 79 and 83%, respectively. G-CSF was given to all patients, and no treatment-related deaths due to myelosuppression occurred. CONCLUSION: The present study is the first to examine the therapeutic outcomes and safety profile of first-line VIP after routine G-CSF use. VIP might be an alternative first-line regimen for patients with disseminated GCC in this G-CSF era.

Prognostic impact of pretreatment C-reactive protein for patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

BACKGROUND: C-reactive protein (CRP) was an independent prognostic factor for metastatic renal cell carcinoma in the cytokine era. However, the impact of CRP on the survival of metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors has not yet been investigated. Therefore, we further evaluated the prognostic impact of CRP for patients with metastatic renal cell carcinoma treated with molecular-targeted agents of tyrosine kinase inhibitors. METHODS: Fifty-two patients were treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma at our institution. Overall, 31 and 21 patients were administered sunitinib and sorafenib, respectively. The prognostic value of all variables, including CRP, for overall survival was assessed using the Cox proportional hazards model. RESULTS: The median baseline CRP level was 4.9 mg/l. In multivariate analysis, CRP was an independent predictor for overall survival as both continuous and categorical variable. The median overall survival times of patients with non-elevated CRP concentration (<8 mg/l) were not reached, compared with those of patients with elevated CRP concentration (8 mg/l or greater) of 15.9 months. There was a significant difference in overall survival rates between the two groups, with 1- and 3-year overall survival rates of 92.8 and 69.3% versus 50.2 and 22.9% for the non-elevated CRP group and the elevated CRP group (p = 0.003), respectively. CONCLUSIONS: CRP has a significant impact on overall survival of patients with metastatic renal cell carcinoma carcinoma treated with tyrosine kinase inhibitors.

Possible improvement of survival with use of zoledronic acid in patients with bone metastases from renal cell carcinoma.

BACKGROUND: Bisphosphonates play an indisputable role in preventing skeletal-related events (SREs) secondary to bone metastases, and also have a direct effect on tumor cells. However, it remains unclear whether bisphosphonates improve overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases. METHODS: Between 1978 and 2010, a total of 45 patients who had RCC metastatic to bone and were classified as intermediate risk according to Memorial Sloan-Kettering Cancer Center criteria were included in this retrospective study. In this cohort, 23 patients received zoledronic acid (ZOL) treatment (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the SRE rate defined as the total number of SREs divided by the total years under study. RESULTS: For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that lower serum calcium (p = 0.0083) and ZOL treatment (p = 0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS than the non-ZOL-treated group (p = 0.0034). Patients in the ZOL-treated group experienced a lower SRE rate than patients in the non-ZOL-treated group (p = 0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in the non-ZOL-treated group did (p = 0.0479). CONCLUSIONS: The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients.