[en] We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year non-recurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88)%, respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers. (author)

[en] According to several guidelines, it is acceptable to spare a bone scan in the patients who are newly diagnosed with low-risk prostate cancer. Our aim is to clarify a suitable group whereby a bone scan could be spared at the initial staging of prostate cancer. Consecutive 857 patients who were newly diagnosed from 2004 through 2009 and received bone scans using technetium 99m methylene diphosphonate at the initial staging were enrolled. The proportion of positive bone metastases by age distribution, prostate-specific antigen level at diagnosis, Gleason score and clinical T stage were evaluated. Univariate and multivariate logistic regression analyses were performed to identify the predictors of positive bone metastases. Of all 857 patients, 40 patients (4.7%) showed bone metastases. Patients with higher age, prostate-specific antigen level, clinical stage and Gleason score showed significantly higher rate of bone metastases (P<0.001). In univariate logistic regression analyses, age, prostate-specific antigen level, clinical stage and Gleason score were independent predictors of bone metastasis. The multivariate analysis showed that both the prostate-specific antigen level >50 ng/ml and the Gleason score ≥4+3 were independent predictors of bone metastases. The incidences of bone metastases in patients with a prostate-specific antigen level of ≤20 ng/ml and Gleason score of ≤6 were reasonably low. Collectively, a bone scan is not necessary as a routine examination for these patients at their initial staging of prostate cancer. (author)

[en] The objective of this study was to clarify the clinical factors including diagnostic imaging findings that may correlate with the histopathological malignancy in primary retroperitoneal tumors. The clinical backgrounds and imaging findings of 22 benign and 24 malignant primary retroperitoneal tumors were retrospectively investigated, and the prognosis of patients with malignant retroperitoneal tumors was assessed. There were significant correlations between the presence of symptoms and malignancy (P<0.01), as well as between the irregularity of tumor margins and malignancy (P<0.01). On dynamic magnetic resonance imaging (MRI), 90% of malignant tumors showed early enhancement either with quick or slow washout, while 75% of benign tumors showed delayed and no enhancement (P<0.002). All malignant and benign paraganglioma showed the same early enhancement with quick washout. Malignant lymphoma showed various enhancement patterns. The 2-year and 5-year cause-specific survival rates of the patients with malignant retroperitoneal tumors were 68.0% and 43.2%, respectively. All malignant lymphoma patients were mainly treated with chemotherapy after being diagnosed histologically. Malignant paraganglioma patients who could not meet complete resection needed chemotherapy for promising survival. The symptoms, the irregularity of the margins, and the specific enhancement pattern on the dynamic MRI may be important predictive factors of the primary malignant retroperitoneal tumors. Histological diagnosis was needed for malignant definition of paraganglioma because both benign and malignant paraganglioma showed similar clinical and imaging findings. Preoperative biopsy should be considered for selection of the appropriate treatment particularly in patients that are likely to have malignant lymphoma that could not be diagnosed definitively by the clinical and imaging findings. (author)

[en] We assessed the variations in stage, prostate specific antigen at diagnosis, Gleason score, risk classification and primary therapy in Japanese prostate cancer patients, and compared with those of the United States (US) patients. Between 2004 and 2006, the distribution of primary therapy and clinical characteristics of 2303 newly diagnosed patients at Nara Medical University and its 23 affiliated hospitals were assessed to compare with those of the Cancer of the Prostate Strategic Urological Research Endeavor data and to clarify the differences in data between the USA and Japan. The proportions of clinical T stage of 3-4, prostate specific antigen at diagnosis >20 ng/ml, Gleason score of 8-10 and high-risk group were greater in our study than those of the Cancer of the Prostate Strategic Urological Research Endeavor data (T3-4, 26.2 vs. 3.5-11.8%; prostate-specific antigen, 34.1 vs. 8.1-27.0%; Gleason score, 29.3 vs. 9.7-12.1%). Regarding the primary treatments, 51% of patients received primary androgen deprivation therapy, 30% underwent radical prostatectomy, 14% received radiation therapy and 2% had watchful waiting in our study, while the corresponding figures in the Cancer of the Prostate Strategic Urological Research Endeavor data were: radical prostatectomy, 44%; radiation therapy, 23%; primary androgen deprivation therapy 20% and watchful waiting 10%. The Japanese prostate cancer patients still have higher prostate-specific antigen at diagnosis, higher Gleason score and higher clinical stage than the US patients. The trends of primary therapy for prostate cancer were different from those in the USA. The higher rate of primary androgen deprivation therapy is characteristic for the Japanese patients. (author)

[en] This study evaluated the clinical utility of the highest bone scan index (BSI), among other BSIs, for each bone metastatic site in patients with bone metastatic castration–resistant prostate cancer (bmCRPC). Thirty patients, diagnosed with bmCRPC by bone scintigraphy, were included. Total BSI, the number of hot spots, and regional BSI on each hot spot from bone scintigraphy at diagnosis with bmCRPC were evaluated by VSBONE BSI®. Highest regional BSI was defined as the highest value among regional BSIs on each hot spot in each patient. Related factors to overall survival and skeletal-related events (SREs) were evaluated using the Cox proportional-hazards model. The median follow-up time from diagnosis with bmCRPC was 29.0 months. During this time, 24 patients died, of which 22 patients died from prostate cancer. On univariate analysis, alkaline phosphatase (ALP) [Hazard ratio (HR): 5.96, 95% confidence interval (CI): 2.05–17.3] and highest regional BSI (HR: 2.01, 95% CI: 1.17–7.05) had significant correlation with overall survival. On multivariate analysis, ALP (HR: 4.79, 95% CI: 1.61–14.2) had significant correlation with overall survival. SREs were found in eight patients. Only the highest regional BSI (HR: 9.99, 95% CI: 2.46–40.6) significantly correlated with SREs on univariate analysis. Highest regional BSI may provide important information regarding prognosis and SREs in patients with bmCRPC

[en] The objective of this study was to assess our initial experience in the treatment of localized prostate cancer using low-dose-rate brachytherapy (LDR-brachytherapy) with iodine-125. One-hundred consecutive patients received LDR-brachytherapy between July 2004 and October 2006. Seventy-six patients were treated with seed implantation alone, whereas 24 patients were treated with a combination of brachytherapy and external beam radiotherapy. The minimal percentage of the dose received by 90% of the prostate gland (%D90), the percentage prostate volume receiving 100% of the prescribed minimal peripheral dose (V100), and the operation time were compared among every 10 consecutive patients. The means of %D90 and V100 were 109.6% and 93.4%, respectively. When compared with the first 10 patients, both D90 and V100 showed significant improvement in the following 10 consecutive patients. Similarly, the mean operation time decreased significantly according to the accumulated number of patients. Our initial experience with the first 100 cases suggests that LDR-brachytherapy needs accumulation of many more patients to obtain high-quality post-implant dosimetric outcomes. (author)

[en] Staging for prostate cancer often includes computed tomography (CT) and bone scan in Japan. We examined the criteria of avoiding unnecessary CT and bone scan for the prostate cancer patients at Matsusaka Chuo General Hospital. Two hundred and eleven patients were newly diagnosed at our institution between 1998 September and 2004 April. We reviewed data from 208 patients who had a staging CT and bone scan. The data was analysed using Gleason score, clinical T-stage and serum prostatic specific antigen (PSA) level. CT detected lymphadenopathy in 19 patients (9.1%), Bone scan detected bone metastasis in 31 patients (14.9%). However there was no lymphadenopathy detected by CT in the patients with 20 ng/ml or less. In the analysis using PSA and Gleason score, there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and Gleason sum 7 or less. In the analysis using PSA and clinical local stage there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and localized lesion (cT1-2). In a new prostate cancer patient CT and bone scan can be avoidable by PSA level of 20 ng/ml or less and cT1-2 or less and Gleason sum 7 or less. (author)

[en] 

Background

We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT).

Methods

In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests.

Results

Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2–64.8%) sensitivity and 72.4% (68.3–76.8%). Urine cytology had 4.5% (0.0–10.7%) sensitivity and 99.8% (99.3–100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up.

Conclusions

The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.

[en] Highlights: • Syndecan-1 is highly expressed in androgen independent prostate cancer cells, PC3. • Syndecan-1 regulates the expression of miR-126 and -149 in prostate cancer cells. • MiR-126 and 149 control cell growth via p21 induction and senescence mechanism. • MiR-126 and 149 promote cell proliferation by suppressing SOX2, NANOG, and Oct4. - Abstract: MicroRNAs (miRNAs) are short (19–24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3′-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by miR-126 and miR-149 is essential for syndecan-1-mediated development of androgen-refractory prostate cancer

[en] To compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)). A total of 218 patients with a median follow-up of 42.5 months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out. Of all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity. The boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity