Docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration for castration-resistant prostate cancer: Long-term outcomes.

OBJECTIVES: To report long-term outcome survival analysis of docetaxel-based chemotherapy combined with dexamethasone in castration-resistant prostate cancer patients (Japan-Multinational Trial Organization Pca10-01 trial). METHODS: The Japan-Multinational Trial Organization Pca10-01 phase II trial was a multicenter, prospective single-arm, phase II trial both in non-metastatic and metastatic castration-resistant prostate cancer patients that was organized by The Japan-Multinational Trial Organization. Patients received 75 mg/m2 of docetaxel (every 21 days) and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. The primary end-point of this additional analysis was overall survival. Secondary end-points were progression-free survival and safety. RESULTS: Between January 2011 and February 2014, a total of 76 chemotherapy-naïve castration-resistant prostate cancer patients were enrolled. The median overall survival time was 42.5 months. The median overall survival time of M1 patients was 40.5 months (M0: not reached). The median progression-free survival time was 13.2 months (M0: 15.7 months and M1: 12.3 months). The multivariate analysis predicting overall survival of M1 patients showed that time to castration-resistant prostate cancer (≥20 months) was an independent parameter (hazard ratio 0.39, P = 0.023). Regarding the safety analysis, 36 out of 74 patients (48.6%) suffered from any grade of adverse events after the protocol treatment, and 18 patients (24.3%) had grade ≥3 adverse events. CONCLUSIONS: Docetaxel-based chemotherapy combined with dexamethasone can achieve excellent survival efficacy not only in M0 castration-resistant prostate cancer patients, but also in M1 castration-resistant prostate cancer patients.

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial.

OBJECTIVES: Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. MATERIALS AND METHODS: This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles). RESULTS: Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%). CONCLUSIONS: The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed.

Evaluation of histopathological findings at the injection site following degarelix administration.

PURPOSE: The aims of the present study were to investigate the incidence of injection site reactions (ISRs) following administration of 240 mg degarelix and identify the risk factors for ISRs. METHODS: This study was conducted in 50 consecutive men treated with degarelix for the first time. ISRs after an initial degarelix dose of 240 mg (administered subcutaneously as two 3 ml subcutaneous injection) were evaluated using the five categories of the Common Terminology Criteria for Adverse Events Version 4 of the National Cancer Institute. We also assessed the differences in patient background between patients with and without an ISR. RESULTS: The mean age of patients and prostate-specific antigen (PSA) level just before degarelix administration were 75.6 and 198.4 ng/ml, respectively. Hormonal therapy with degarelix was administered for the first time to 33 patients; 11 of the 50 patients were receiving an oral steroid, 6 for prostate cancer, 1 for hematological disease, and 4 for allergic conditions. ISRs were observed in 25 patients, and all of the ISRs were categorized as grade 1 or 2; however, 2 patients discontinued this procedure due to the ISR. Significant differences in the first experience with subcutaneous therapy (p = 0.007) and rate of combination with a steroid (p = 0.017) were observed between patients with and without ISRs. CONCLUSION: The incidences of ISRs in patients receiving subcutaneous therapy for the first time and in patients also receiving an oral steroid were 64 and 18 %, respectively. Patients should be provided with information concerning the possible occurrence of ISR due to degarelix prior to the administration, particularly patients who are not receiving steroids and patients who have no experience with subcutaneous injections.

Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer.

BACKGROUND: The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). METHODS: We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m(2) was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm(3) and defined FN as an ANC of <1000/mm(3) with a body temperature of >38.3 °C. RESULTS: The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6% of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥ 75 years (p = 0.002), number of comorbidities ≥ 1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥ 75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥ 75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). CONCLUSIONS: Patients aged ≥ 75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance.

Prognostic value of preoperative multiparametric magnetic resonance imaging (MRI) for predicting biochemical recurrence after radical prostatectomy.

OBJECTIVE: To evaluate the suitability of preoperative multiparametric magnetic resonance imaging (MRI) positivity as a predictor of biochemical recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: We reviewed the clinical records of patients who underwent either standard RP or laparoscopic RP between January 2005 and December 2009 at our institution. Patients who received radiotherapy or androgen deprivation therapy before surgery were excluded. A total of 314 patients met the study inclusion criteria. Cox proportional hazard regression models were used for analyses. In accordance with the criteria in the established guidelines, a radiologist scored the probability of the presence of prostate cancer using a five-point scale of diagnostic confidence level. The highest confidence level of any pulse sequence was considered as the evaluation result. RESULTS: MRI positivity was significantly associated with a high clinical stage (cT ≥ 2; P = 0.039), a high positive biopsy core rate (≥0.2; P < 0.001), a high biopsy Gleason score ([GS] ≥8; P < 0.001) and a high pathological GS (≥8; P = 0.005). Univariate analysis and multivariate analysis showed that MRI positivity was a prognostic indicator in the analysis that included only preoperative variables and also in the analysis including preoperative and pathological variables. CONCLUSION: Multiparametric MRI positivity can independently predict biochemical recurrence after RP.

A prospective longitudinal survey of erectile dysfunction in patients with localized prostate cancer treated with permanent prostate brachytherapy.

PURPOSE: Few studies have evaluated changes in erectile function with time before and after prostate brachytherapy using the International Index of Erectile Function-15, a sensitive, validated tool for assessing male sexual dysfunction. In this prospective study we evaluated the natural history of erectile function after prostate brachytherapy without supplemental therapy (external beam radiotherapy, phosphodiesterase-5 inhibitors or androgen deprivation therapy) using the International Index of Erectile Function-15. MATERIALS AND METHODS: We identified 119 patients who were followed at least 12 months after prostate brachytherapy between 2004 and 2010. Sexual and erectile function status were assessed before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15. RESULTS: Mean total International Index of Erectile Function-15 score, and scores on the erectile function, orgasmic function, sexual desire and intercourse satisfaction domains 3 months after brachytherapy were significantly lower than at baseline (p <0.05). They remained lower until 36 months after prostate brachytherapy. Erectile function was maintained 12 months after brachytherapy in 16 of the 48 men (33.3%) with a baseline erectile function domain score of 11 or greater. There was no significant difference in clinical features except the age of patients who maintained the erectile function domain score and their counterparts 12 months after brachytherapy. Multivariate analysis revealed that age 70 years or greater was the only predictive factor for deteriorating erectile function after brachytherapy (p = 0.035). CONCLUSIONS: Findings indicate a global decrease in all domains of the International Index of Erectile Function-15 score 12 months after prostate brachytherapy. Also, patient age may influence the preservation of brachytherapy related potency.

Burden of overactive bladder symptom on quality of life in stroke patients.

AIMS: Overactive bladder (OAB) affects the daily life of many stroke victims. In contrast to urinary incontinence, little is known about the prevalence and risk factors for OAB among stroke patients. Therefore, we conducted a questionnaire survey and analyzed the results together with the clinical data and MRI findings. METHODS: A total of 500 volunteer patients with chronic-phase stroke were enrolled. The overactive bladder symptom score (OABSS), Short Form 8 (SF-8) health survey questionnaire, and some key international questionnaires about urinary dysfunction were assessed. RESULTS: We diagnosed 141 patients (28%) with OAB, among whom 103 (73%) had never been treated for their symptoms. Patients with OAB showed lower scores in both the physical and mental components of the SF-8, which suggested the burden of OAB on the quality of life of stroke patients. Advanced age and male gender were closely related to high OABSS. The modified Rankin Scale (mRS) was positively correlated with OABSS. Patients with cerebral infarction and those with intracerebral hemorrhage showed a similarly high OABSS. The severity of deep white-matter hyperintensity on MRI, classified by the 4-grade Fazekas scoring system, was significantly associated with high OABSS irrespective of presence of accompanying infarcts. Patients with cerebral infarcts in the region of anterior circulation showed a higher OABSS than those with cerebral infarcts in the posterior circulation. CONCLUSIONS: Based on the present risk analysis, patient care should be preferentially focused on the detection and treatment of OAB to improve the quality of life of stroke patients.

Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.

OBJECTIVE: To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. METHODS: Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. RESULTS: Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. CONCLUSIONS: Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

[Prospective survey of erectile dysfunction after external beam radiotherapy for prostate cancer].

OBJECTIVE: We prospectively evaluated the effect of external beam radiotherapy on erectile function in patients with localized or locally advanced prostate cancer using the Japanese version of the International Index of Erectile Function (IIEF) survey. PATIENTS AND METHODS: From 2000 to 2007, we identified 55 patients who underwent external beam radiotherapy at our institution for localized or locally advanced prostate cancer and could respond to the IIEF survey. The patients did not receive neo- and/or adjuvant hormone therapy and they were followed-up for at least 12 months after radiotherapy. Mean patient age was 69 years and the mean PSA level before radiotherapy was 24.9 ng/ml. RESULTS: First we evaluated the change of the erectile function domain score over time before and after radiotherapy. The population of severe erectile dysfunction (ED) increased while those with no or mild ED decreased after radiotherapy. The erectile function and intercourse satisfaction domain score of the IIEF declined significantly after radiotherapy, however, the orgasmic function, sexual desire, and overall satisfaction domain scores did not change after external beam radiation. Of the 34 patients who had erectile function at baseline, 10 patients could maintain erectile function 12 months after radiotherapy. Though there were no significant differences in clinical features between patients who could maintain erectile function and those who had worsening erectile function 12 months after radiotherapy, the sexual desire domain score before radiotherapy was significantly higher in patients who could maintain erectile function than their counterparts. CONCLUSION: Using the IIEF survey, external beam radiation was found to affect erectile function in patients with localized or locally advanced prostate cancer.

Prognostic stratification in patients who received hormonal therapy for prostate-specific antigen recurrence after radical prostatectomy.

The present study was undertaken to investigate the predictors in patients who received hormonal therapy (HT) for prostate-specific antigen recurrence (PSAR) after surgery. Predictors for the progression-free survival were assessed in 55 patients who received HT for PSAR after surgery. In multivariate analysis, primary Gleason grade > or =4 and PSA doubling time (PSA-DT) <6 months were independent predictors. The patients were stratified into low-risk group (Gleason grade <4 and PSA-DT > or =6), high-risk group (Gleason grade > or =4 and PSA-DT <6) and intermediate-risk group (all others). In the intermediate- and high-risk groups, progression-free survival rate was significantly higher in patients with PSA level <2 than in those with PSA level > or =2 at the initiation of HT. Primary Gleason grade > or =4 and PSA-DT <6 months are independent predictors. Patients in the intermediate- and high-risk groups may benefit from early HT for PSAR after surgery.

Docetaxel in combination with prednisolone for hormone refractory prostate cancer.

OBJECTIVE: The objective of this study was to evaluate the efficacy and toxicity of docetaxel in combination with prednisolone in Japanese patients with hormone refractory prostate cancer. METHODS: Twenty patients with hormone refractory prostate cancer (HRPC) were administered a treatment regimen consisting of docetaxel 75 mg/m(2) once every 3 or 4 weeks and prednisolone 5 mg twice daily at our institution between 2006 and 2008. RESULTS: The patients received a median of 5.5 cycles of treatment (range, 2-12 cycles). Nine of the 20 patients (45%) had a >or=50% decrease in serum prostate-specific antigen (PSA). The median duration of response was 4 months (range, 1-11 months). The number of cycles performed, the presence of bone metastasis and the extent of disease had statistically significant associations with the response. Three patients had a transient PSA rise among the patients who ultimately had a response. Grade 3/4 leukopenia and neutropenia occurred in 80.0% and 85.0% of the patients, respectively. Interstitial pneumonia occurred in only one patient; however, the patient recovered. Finally, no treatment-related deaths were seen during the observation period. CONCLUSIONS: The combination of docetaxel 75 mg/m(2) every 3 weeks and prednisolone 10 mg daily was effective and well tolerated in Japanese patients with HRPC. The results of this study suggest that a decision concerning discontinuation of this treatment should be carefully considered because a transient PSA rise was observed. Although interstitial pneumonia was rare, the potential risk of its development should be taken into consideration.

Contrast-enhanced ultrasonography of the prostate with Sonazoid.

OBJECTIVE: The diagnosis of prostate cancer is based on the results of ultrasonography-guided needle biopsy of the prostate, but cancer foci are often not visible in conventional transrectal ultrasonography. Sonazoid is a new microbubble contrast agent. The purpose of our study was to compare areas of contrast material enhancement in the prostate at ultrasonography with whole-mount radical prostatectomy specimens to determine if the use of Sonazoid improves the detection rate of prostate cancer. METHODS: Fifty patients with biopsy-proven cancer of the prostate who were scheduled to undergo radical prostatectomy were recruited for this study. The day before the operation, each patient was evaluated with ultrasonography at baseline and again during intravenous infusion of Sonazoid. A map of ultrasonography findings was created prospectively at the time of imaging. Following radical prostatectomy, independent mapping of the pathologic results was performed and the maps were compared. RESULTS: Ultrasonography evaluation at baseline demonstrated that at least one focus of cancer was identified in 20 of the 50 subjects (40.0%). Meanwhile at least one cancer focus was enhanced in 31 of the 50 patients (62.0%) when Sonazoid was used. The combination of baseline grayscale imaging and contrast-enhanced imaging allowed identification of at least one focus of cancer in 40 patients (80.0%). Contrast-enhanced ultrasonography can improve sensitivity, especially for the detection of large cancer, peripheral zone cancer and highly malignant cancer. CONCLUSIONS: Our study has demonstrated significantly improved detection of prostate cancer with the combination of baseline grayscale imaging and contrast-enhanced imaging compared with conventional ultrasonography techniques only, and this technique may be applicable to targeted biopsy.

Prostate-specific antigen 'bounce' after permanent 125I-implant brachytherapy in Japanese men: a multi-institutional pooled analysis.

OBJECTIVE: To examine the incidence, timing, and magnitude of the prostate-specific antigen (PSA) level 'bounce' after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer. PATIENTS AND METHODS: A multi-institutional pooled analysis was carried out in 388 consecutive patients with T1-T2N0M0 prostate cancer treated with (125)I-seed implant BT with no hormonal therapy or external beam radiotherapy. All patients had >or=1 year of follow-up and at least three follow-up PSA level measurements. Three definitions of PSA bounce were used: definition A, a PSA level rise of 0.1 ng/mL; definition B, a PSA level rise of 0.4 ng/mL; and definition C, a PSA level rise of 35% over the previous value, followed by a subsequent fall. RESULTS: The actuarial likelihood of having PSA bounce at 24 months was 50.8% for definition A, 23.5% for definition B, and 19.4% for definition C. The median time to develop PSA bounce was 12 months for definition A, 18 months for definition B, and 18 months for definition C. There was a PSA bounce magnitude of 2 ng/mL in 5.3% of patients, and 95.3% of PSA bounce occurred within 24 months after (125)I-BT. Among the before and after (125)I-BT factors, clinical stage, initial PSA level, and Gleason score did not predict for PSA bounce using any definition; only being younger predicted for PSA bounce on multivariate analysis (P < 0.001). CONCLUSIONS: PSA bounce is a common phenomenon after (125)I-BT and occurred at a rate of 19-51% in the Japanese men who underwent (125)I-BT, depending on the definition used. It is more common in younger patients, and early PSA bounce should be considered when assessing a patient with a rising PSA level after (125)I-BT, before implementing salvage interventions. Furthermore, PSA bounce magnitude might be lower in Japanese than in Caucasian patients.

Prediction of PSA bounce after permanent prostate brachytherapy for localized prostate cancer.

BACKGROUND: We aimed to calculate the frequency and features of the development of a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, to correlate the bounce with clinical and dosimetric factors and to identify factors that predict PSA bounce. METHODS: PSA bounce was evaluated in 86 patients with T1-T2 prostate cancer who underwent radioactive seed implantation using iodine-125 (I-125) without hormonal therapy or external-beam radiation therapy (EBRT) from September 2004 to December 2007. A PSA bounce was defined as a rise of at least 0.4 ng/ml greater than a previous PSA level with a subsequent decline equal to, or less than, the initial nadir. RESULTS: Calculated by the Kaplan-Meier method, the incidence of PSA bounce at a 2-year follow-up was 26%. Median time to the PSA bounce was 15 months. Univariate analysis demonstrated that age, dose received by 90% of the prostate gland (D90), volume of gland receiving 100% of the prescribed dose (V100), and V150 were significantly associated with the PSA bounce, while pretreatment PSA level, Gleason score, pretreatment prostate volume, clinical T stage, and V200 were not. In multivariate analysis, age 67 years or less and D90 more than 180 Gy were identified as independent factors for predicting the PSA bounce (P < 0.05). CONCLUSION: PSA bounce is not a rare phenomenon after prostate brachytherapy. It is more common in younger patients and patients receiving higher doses of radiation.

Prognostic Value of Pretreatment Albumin-to-Globulin Ratio in Patients With Non-Muscle-Invasive Bladder Cancer.

PURPOSE: To investigate the relationship between albumin-to-globulin ratio (AGR) and oncologic outcomes in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We identified 364 patients with primary NMIBC who underwent transurethral surgery between 2000 and 2015. The association between pretreatment AGR and clinicopathologic variables, including oncologic outcomes, was statistically evaluated. RESULTS: One hundred twenty patients (33.0%) experienced at least one tumor recurrence, and 23 (6.3%) developed muscle-invasive disease. The median (interquartile range) pretreatment AGR was 1.73 (1.53-1.89). The Kaplan-Meier curve revealed that tumor recurrence was strongly predicted in patients with pretreatment AGR < 1.6, and similar results were observed for disease progression (P < .01 and P < .01, respectively). On multivariate analysis, we found that pretreatment AGR < 1.6 is an independent risk factor for tumor recurrence (hazard ratio, 0.53; P < .01). On univariate analysis, pretreatment AGR < 1.6 was also associated with disease progression (hazard ratio, 0.24; P < .01). CONCLUSION: Low pretreatment AGR is an independent risk factor for tumor recurrence and is one risk factor for disease progression in NMIBC patients. This inexpensive and easily accessible biomarker may become useful in selecting patients with NMIBC with higher risk of recurrence and progression.

Rectal morbidity following I-125 prostate brachytherapy in relation to dosimetry.

BACKGROUND: To investigate rectal morbidity after I-125 prostate brachytherapy and to analyze predictive factors of rectal morbidity. METHODS: A group of 227 consecutive patients with localized prostate cancer were treated with I-125 prostate brachytherapy with or without external beam radiotherapy (EBRT) between September 2003 and January 2005. Rectal morbidity (diarrhea, bleeding and pain) was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Dosimetry was based on computerized tomography (CT) scan 1 month post-implant. The clinical, treatment-related and dosimetric factors were evaluated for the risk of grade 2 rectal morbidity. Rectal dosimetric factors included the rectal volume that received >100% and 150% of the prescribed dose, and the maximal rectal dose which was defined as the sum of the minimal dose received by 1% of the rectum volume and the prescribed dose of EBRT. RESULTS: Grade 2 rectal bleeding occurred in 10 (4.4%): for nine patients within the first year and for one patient between the first and second year. Grade 2 diarrhea occurred in one patient (0.4%) within the first year. No patient reported grade 2 pain. In the univariate analysis with grade 2 rectal bleeding, there were significant correlations with number of seeds, supplemental EBRT, and all of the rectal dosimetric parameters. On subsequent multivariate analysis, the only significant factor was the maximal rectal dose (P < 0.001). Rectal dose > 160 Gy was correlated to grade 2 rectal morbidity. All the patients with rectal dose > 160 Gy received EBRT. CONCLUSIONS: Manifestations of rectal morbidity are acceptable events after I-125 prostate brachytherapy. Rectal dose-volume histogram for the brachytherapy is a predictive method for assessing the risk of developing grade 2 rectal bleeding. Delivery of the rectal dose should not exceed 160 Gy in order to avoid rectal complications.

Comparison of intraoperative ultrasound with postimplant computed tomography--dosimetric values at Day 1 and Day 30 after prostate brachytherapy.

PURPOSE: To compare the results of intraoperative dosimetry with those of postimplant computed tomography (CT)-based dosimetry after (125)I prostate brachytherapy. METHODS AND MATERIALS: We treated 412 prostate cancer patients with (125)I prostate brachytherapy, with or without external beam radiotherapy at our institution. Neoadjuvant hormone therapy was administered to 331 patients (80.3%). Implantation was performed using an intraoperative interactive technique. Postimplant dosimetry was performed on Day 1 and Day 30 using CT imaging. The dosimetric results for the prostate, urethra, and rectum were compared among intraoperative ultrasound, and CT scans of Day 1 and Day 30. RESULTS: The mean intraoperative minimal dose received by 90% of the prostate volume (D(90)) was 118.8% of the prescribed dose vs. 106.4% for Day 1 (p < 0.01) and 119.2% for Day 30 (p = 0.25). There were no significant correlations between the intraoperative D(90) and the postimplant D(90) values (intraclass correlation coefficients=0.42 and 0.33 for Day 1 and Day 30, respectively). Prostatic edema at Day 1 had the largest effect on the Day 1 D(90) (p < 0.01). The factor significantly affecting the Day 30 D(90) was neoadjuvant hormone therapy (p < 0.01). The mean Day 30 D(90) for the hormone-treated patients was 117.9%, compared with 124.6% for those who remained hormone naïve. The intraoperative and postimplant dosimetric values differed significantly for the urethra and rectum. CONCLUSIONS: Our results demonstrate that there are no significant differences between the D(90) assessments obtained intraoperatively and at Day 30 postoperatively. Furthermore, there are no definite correlations between intra- and postimplantation dosimetric values. Other D(90) values differed significantly between the intraoperative and postimplant dosimetry. This study suggests that dosimetry has negligible clinical utility for informing patients, at discharge, of whether or not their implants are adequate.

Characterizing intermediate-risk non-muscle-invasive bladder cancer: Implications for the definition of intermediate risk and treatment strategy.

PURPOSE: Patients with intermediate-risk non-muscle-invasive bladder cancer have traditionally been defined as those not included in the low- or high-risk groups. Therefore, the intermediate-risk group consists of heterogeneous patients. MATERIALS AND METHODS: We reviewed 326 patients diagnosed with intermediate-risk tumors. We subclassified these patients into 3 groups according to their clinical courses. Group A included patients with initial and multiple low-grade tumors (N = 170). Group B consisted of patients with a low-grade tumor that recurred after a low-risk tumor (N = 97), and Group C consisted of patients with a low-grade tumor that recurred after a high-risk tumor (N = 59). RESULTS: The 2-year recurrence-free survival rate was significantly lower in Group C (42%) than in Groups A (69%, P<0.01) and B (70%, P<0.01). Regarding progression-free survival, no significant differences were observed among the groups. In total, 167 patients received adjuvant bacillus Calmette-Guérin (BCG), and 39 received adjuvant chemotherapy instillations. In Groups A and B, there were no significant differences in efficiency against tumor recurrence between BCG and chemotherapy. In Group C, the 5-year recurrence-free survival rate was 65% in patients receiving BCG, which was significantly higher when compared with patients receiving chemotherapy (P = 0.01). Furthermore, Group C included 11 BCG refractory cases, 5 of whom later experienced stage progression during follow-up. CONCLUSION: Our subclassification analysis suggested that intermediate-risk tumors that recurred after a high-risk tumor (Group C) should be treated with adjuvant BCG therapy, owing to the high probability of subsequent recurrence. Furthermore, the definition of intermediate risk may include some BCG refractory cases.

Female Functional Constipation Is Associated with Overactive Bladder Symptoms and Urinary Incontinence.

This noninterventional cross-sectional study aims to assess the association between functional constipation (FC) and urinary symptoms in female patients with no treatment for urination and defecation. The Rome III criteria for evaluation of defecation, Overactive Bladder Symptom Score (OABSS) for evaluation of urinary symptoms, and clinical features were investigated in 145 female patients. Latent FC and moderate to severe overactive bladder (OAB) were defined on the basis of positivity for two or more of the Rome III criteria and an OABSS ≥ 6 with OABSS Q3 ≥ 2, respectively. In 60 latent FC patients, the OABSS was higher (5.0 versus 3.2, p = 0.001), and concurrent moderate to severe OAB symptoms and OAB with urinary incontinence were more frequent than those in 85 nonlatent FC patients (33.3 versus 10.6%, p = 0.001, and 31.7 versus 7.1%, p < 0.001). Multivariate analysis demonstrated that moderate to severe OAB symptoms were a significant associated factor of latent FC (odds ratio (OR) = 4.125, p = 0.005), while latent FC was the only associated factor of moderate to severe OAB and OAB with urinary incontinence (OR = 4.227, p = 0.005 and OR = 4.753, p = 0.004). In conclusion, moderate to severe OAB symptoms are correlated with FC. Moreover, FC is related to moderate to severe OAB symptoms and to OAB with urinary incontinence.

[Assessment criteria of lower urinary tract symptom severity for general practitioners].

OBJECTIVES: We conducted a preliminary study to examine the validity of assessment criteria of lower urinary tract symptoms (LUTS) severity for general practitioners (GPs). MATERIALS AND METHODS: This study included 194 patients with LUTS, who visited the urology clinics in three hospitals. In 177 who completed International Prostate Symptom Score (I-PSS), International Consultation on Incontinence Questionnaire : Short-Form (ICIQ-SF), frequency-volume chart, uroflowmetry and post-void residual urine measurement, three overall grades (mild, moderate and severe) of LUTS were determined using the newly-developed assessment criteria for GPs. The relationship between diagnoses and treatments by the urologists, and overall LUTS grades were examined. RESULTS: All of the 70 patients with "severe" grade and 68 (94%) of 72 with "moderate" grade were diagnosed as having urination problems. Sixty-eight (97%) with "severe" grade and 64 (89%) with "moderate" grade were treated with fluid restriction, behavioral therapy, and/or drug therapy. Of 35 with "mild" grade, 17 (49%) were diagnosed as having normal urination. In this grade, eight patients (23%) were treated with fluid restriction and 15 (43%) with drug therapy. CONCLUSIONS: This preliminary study revealed that our criteria of LUTS severity for GPs were useful to determine whether the elderly patients should be treated or not. It is necessary to examine the validity of the criteria in a model in which GPs participate.