Survival outcomes of radium-223 therapy for metastatic castration-resistant prostate cancer following national health insurance reimbursement in Taiwan.

BACKGROUND: Radium-223 dichloride (Ra-223) prolongs overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases. However, there is considerable variation in outcomes among individuals. We aimed to evaluate the prognostic determinants associated with patient survival following National Health Insurance (NHI) reimbursement for Ra-223 therapy in Taiwan. METHODS: Patients with mCRPC who underwent Ra-223 treatment at Taipei Veterans General Hospital were retrospectively enrolled. Each intravenous Ra-223 dose was administered at 55 kBq/kg at four-week intervals. Clinical outcomes were obtained from medical records; potential prognostic factors for survival were assessed. Kaplan-Meier analysis was used to generate cumulative survival curves; between-group differences were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05. RESULTS: Seventy-six patients underwent Ra-223 therapy; 62 patients received NHI reimbursement and the remainder self-paid. Fifty patients (65.8%) completed six cycles of treatment; 26 (34.2%) received 1‒5 cycles. Mortality occurred in 47 patients. Factors significantly associated with survival included ≦ five bone metastases (p = 0.0018), baseline prostate-specific antigen (PSA) ≦ 36 ng/mL (p = 0.0004), baseline alkaline phosphate (ALP) < 115 U/L (p = 0.0007), and baseline hemoglobin (Hb) > 12 g/dL (p = 0.0029). Patients who completed six cycles of treatment achieved significantly higher OS compared to those who did not (p < 0.0001). There has been a 4.4-fold increase in the number of patients since reimbursement began; there was no significant difference in OS between patients who received NHI reimbursement and those who self-paid. CONCLUSION: Administration of Ra-223 demonstrates considerable potential to extend the survival of patients with mCRPC. Survival outcomes may be influenced by various prognostic factors. However, no significant difference in OS was observed subsequent to reimbursement of Ra-223 therapy for mCRPC through the NHI system in Taiwan.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Is Robotic Superior to Laparoscopic Approach for Radical Nephroureterectomy with Bladder Cuff Excision in Treating Upper Urinary Tract Urothelial Carcinoma?

Background: Laparoscopic nephroureterectomy (LNU) has become popular in treating upper urinary tract urothelial carcinoma (UTUC) and an emerging trend was observed in robotic approaches. Therefore, we compared robot-assisted radical nephroureterectomy (RANU) and LNU for the treatment of UTUC. Materials and Methods: This observational and retrospective case-series study included UTUC patients who underwent LNU or RANU. A pure laparoscopic approach was adopted in the LNU treatment group, and bladder cuff excision (BCE) was performed mostly with the open approach. Either the da Vinci Si or Xi surgical system was used for RANU. Extravesical BCE was performed, and bladder defects were closed intracorporeally. Perioperative and oncologic outcomes were compared between the LNU and RANU groups. Results: A total of 231 patients who underwent RANU (n = 87) or LNU (n = 144) were included. No significant differences were noted between the groups in terms of demographics, tumor characteristics, operative time, catheter time, or complications. Compared with LNU, RANU had a lower intraoperative blood loss (30 vs. 150 mL, p < 0.001) and shorter postoperative hospital stay (8 vs. 9 days, p = 0.009). The 5-year overall survival, cancer-specific survival, and bladder recurrence-free survival were comparable between the groups. Conclusion: Compared with LNU, RANU had similar perioperative and oncologic outcomes but was superior in terms of intraoperative blood loss and postoperative length of hospital stay. However, considering the potential biases owing to the heterogeneity of our cases, the interpretation of the results must be very cautious.

Management of metastatic renal cell carcinoma following prior vascular endothelial growth factor-targeted therapy: A real-world retrospective study from Taiwan.

BACKGROUND: There are limited real-world data to guide the sequencing of targeted therapies in patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to characterize real-world treatment patterns (primarily second line [2L]) after prior vascular endothelial growth factor (VEGF) targeted therapy in an unselected mRCC population from Taiwan between 2013 and 2017. Treatment-related adverse events (TRAEs) and their management were also evaluated (NCT03633579). METHODS: This retrospective cohort study included patients who had received prior VEGF-targeted therapy and were treated at the National Taiwan University Hospital or the Taipei Veterans General Hospital between June 2013 and December 2017. Outcomes were characterized using descriptive statistics. RESULTS: Overall, 27 patients were included: 22 (81.5%) male; mean standard deviation (SD) age, 63.1 (11.1) years; 18 (66.7%) initiated targeted therapy during the year immediately following mRCC diagnosis. All patients received sunitinib as their first-line (1L) targeted therapy, with a median (range) treatment duration of 10 (1.8-65.8) months. The most common reason for discontinuing 1L sunitinib was disease progression (88.9% of patients). Everolimus was the most common 2L targeted therapy, in 23 patients (85.2%); 4 patients (14.8%) received 2L axitinib. Median (range) duration of 2L therapy was 4.0 (0.1-30.5) months for everolimus and 4.2 (0.5-9.2) months for axitinib. Ten TRAEs were reported among seven patients receiving 2L everolimus: hypertension (n = 5), hand-foot syndrome (n = 2), hyperglycemia (n = 1), renal failure (n = 1), and interstitial pneumonitis (n = 1). The majority (80%) of TRAEs were managed in the outpatient setting. No TRAEs were reported in the axitinib group. CONCLUSION: Real-world management of patients with mRCC in Taiwan broadly aligned with clinical guidelines and national reimbursement policy at the time of the study. These findings may be a useful reference for assessing the implications of evolving mRCC management approaches in Taiwan.

Fractionated deep-inspiration breath-hold ZTE Compared with Free-breathing four-dimensional ZTE for detecting pulmonary nodules in oncological patients underwent PET/MRI.

The zero echo time (ZTE) technique has improved the detection of lung nodules in PET/MRI but respiratory motion remains a challenge in lung scan. We investigated the feasibility and performance of fractionated deep-inspiration breath-hold (FDIBH) three-dimensional (3D) ZTE FDG PET/MRI for assessing lung nodules in patients with proved malignancy. Sixty patients who had undergone ZTE FDG PET/MRI and chest CT within a three-day interval were retrospectively included. Lung nodules less than 2 mm were excluded for analysis. Two physicians checked the adequacy of FDIBH ZTE and compared the lung nodule detection rates of FDIBH 3D ZTE and free-breathing (FB) four-dimensional (4D) ZTE, with chest CT as the reference standard. FDIBH resolved the effect of respiratory motion in 49 patients. The mean number and size of the pulmonary nodules identified in CT were 15 ± 31.3 per patient and 5.9 ± 4.6 mm in diameter. The overall nodule detection rate was 71% for FDIBH 3D ZTE and 70% for FB 4D ZTE (p = 0.73). FDIBH 3D ZTE significantly outperformed FB 4DZTE in detecting lung base nodules (72% and 68%; p = 0.03), especially for detecting those less than 6 mm (61% and 55%; p = 0.03). High inter-rater reliability for FDIBH 3D ZTE and FB 4D ZTE (k = 0.9 and 0.92) was noted. In conclusion, the capability of FDIBH 3D ZTE in respiratory motion resolution was limited with a technical failure rate of 18%. However, it could provide full expansion of the lung in a shorter scan time which enabled better detection of nodules (< 6 mm) in basal lungs, compared to FB 4D ZTE.

The Prostate Health Index aids multi-parametric MRI in diagnosing significant prostate cancer.

To evaluate the performance of the Prostate Health Index (PHI) in magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion prostate biopsy for the detection of clinically significant prostate cancer (csPCa). We prospectively enrolled 164 patients with at least one Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) ≥ 3 lesions who underwent MRI-TRUS fusion prostate biopsy. Of the PSA-derived biomarkers, the PHI had the best performance in predicting csPCa (AUC 0.792, CI 0.707-0.877) in patients with PI-RADS 4/5 lesions. Furthermore, the predictive power of PHI was even higher in the patients with PI-RADS 3 lesions (AUC 0.884, CI 0.792-0.976). To minimize missing csPCa, we used a PHI cutoff of 27 and 7.4% of patients with PI-RADS 4/5 lesions could have avoided a biopsy. At this level, 2.0% of cases with csPCa would have been missed, with sensitivity and NPV rates of 98.0% and 87.5%, respectively. However, the subgroup of PI-RADS 3 was too small to define the optimal PHI cutoff. PHI was the best PSA-derived biomarker to predict csPCa in MRI-TRUS fusion prostate biopsies in men with PI-RADS ≥ 3 lesions, especially for the patients with PI-RADS 3 lesions who gained the most value.

Prostate health index density predicts aggressive pathological outcomes after radical prostatectomy in Taiwanese patients.

BACKGROUND: There are models to predict pathological outcomes based on established clinical and prostate-specific antigen (PSA)-derived parameters; however, they are not satisfactory. p2PSA and its derived biomarkers have shown promise for the diagnosis and prognosis of prostate cancer (PCa). The aim of this study was to investigate whether p2PSA-derived biomarkers can assist in the prediction of aggressive pathological outcomes after radical prostatectomy (RP). METHODS: We prospectively enrolled patients who were diagnosed with PCa and treated with RP between February 2017 and December 2018. Preoperative blood samples were analyzed for tPSA, free PSA (fPSA), percentage of fPSA (%fPSA), [-2]proPSA (p2PSA), and percentage of p2PSA (%p2PSA). Prostate health index (PHI) was calculated as (p2PSA/fPSA) × âˆštPSA. Prostate volume was determined by transrectal ultrasound using the ellipsoid formula, and PHI density was calculated as PHI/prostate volume. The areas under the receiver operating characteristic curve were estimated for various PSA/p2PSA derivatives. Aggressive pathological outcomes measured after RP were defined as pathological T3 or a Gleason score (GS) >6 as determined in RP specimens. RESULTS: One hundred and forty-four patients were included for analysis. Postoperative GS was >6 in 86.1% of the patients, and pT stage was T3a or more in 54.2%. Among all PSA- and p2PSA-derived biomarkers, PHI density was the best biomarker to predict aggressive pathological outcomes after RP. The odds ratio of having an aggressive pathological outcome of RP was 8.796 (p = 0.001). In multivariate analysis, adding %fPSA to base model did not improve the accuracy (area under curve), but adding PHI and PHI density to base model improved the accuracy by 2% and 16%, respectively, in predicting pT3 stage or GS ≥ 7. The risk of pT3 stage or GS ≥ 7 was 20.8% for PHI density <1.125, and 64.6% for PHI density >1.125 (sensitivity: 74.6% and specificity: 88.9%). CONCLUSION: PHI density may further aid in predicting aggressive pathological outcomes after RP. This biomarker may be useful in preoperative counseling and may have potential in decision making when choosing between definitive treatment and active surveillance of newly diagnosed PCa.

Prostate Health Index outperforms other PSA derivatives in predicting a positive biopsy in men with tPSA <10 ng/mL: Largest prospective cohort in Taiwan.

BACKGROUND: Few prospective studies have focused on the performance of the Prostate Health Index (PHI) in Asian populations. Therefore, we aimed to evaluate the performance of the PHI in predicting prostate cancer (PCa) compared with standard prostate-specific antigen (PSA) tests. METHODS: We prospectively enrolled patients with suspected PCa with a total PSA (tPSA) level 4 to 10 ng/mL or tPSA <4 ng/mL and a suspicious digital rectal examination between February 2017 and September 2018. All of the patients underwent a 12-core transrectal ultrasound-guided prostate biopsy. Prebiopsy blood samples were analyzed for tPSA, free PSA (fPSA), percentage of fPSA (%fPSA), [-2]proPSA (p2PSA), and percentage of p2PSA (%p2PSA). The PHI was calculated as (p2PSA/fPSA) × âˆštPSA. The areas under the receiver operating characteristic curve (AUCs) were estimated for the PSA derivatives in addition to their specificities at a prespecified sensitivity of 90%. RESULTS: Of the 307 enrolled patients, 95 (30.9%) had PCa on biopsy. Excluding fPSA, all of the PSA derivatives were significantly different between the positive and negative biopsy groups. Of the various derivatives, the PHI (AUC: 0.783) showed the best performance in predicting the results of the initial biopsy compared with tPSA (AUC: 0.611). At a sensitivity of 90%, the PHI had the best specificity of 46.7% compared with 23.2% for tPSA. Using a PHI cutoff value of 35.15 for biopsy, 108 (35.2%) patients could have avoided undergoing a biopsy. To detect Gleason score ≥ 7 disease at 90% sensitivity, the threshold for PHI was 36.96 with a specificity of 52.1%. CONCLUSION: PHI was the best biomarker among the PSA derivatives in predicting PCa at biopsy in men with tPSA < 10 ng/mL. The risk of a Gleason score ≥ 7 increased with increasing PHI.

Transrectal ultrasound-guided prostate biopsy in Taiwan: A nationwide database study.

BACKGROUND: For patients with an elevated prostate specific antigen (PSA) level or a suspected lesion detected by digital rectal examination, transrectal ultrasound-guided (TRUS) prostate biopsy is the standard procedure for prostate cancer diagnoses. In Taiwan, TRUS prostate biopsy has not been well-studied on a nationwide scale. This article aimed to study TRUS prostate biopsy in Taiwan and its related complications, according to the claims generated through the National Health Insurance (NHI) program. METHODS: We applied for access to claims from the NHI Research Database of Taiwan of all patients who visited the urology clinic during the period of 2006 to 2010. In the 5-year urology profile, we obtained all records, which included admission and ambulatory clinical records. The definition of TRUS biopsy included codes for ultrasound-guided procedure and for prostate puncture; other codes involving complications such as postbiopsy voiding difficulty, significant bleeding, or infection requiring treatment were also included. Risk factors included age, diagnosis of prostate cancer, hospitalization or nonhospitalization, and the Charlson Comorbidity Index (CCI; with a value of 0, 1, 2 or ≥ 3). Descriptive and comparative analyses were also performed. RESULTS: In the 5-year urology profile, 12,968 TRUS biopsies performed of which 6885 were in-patient procedures and 6083 were ambulatory clinic procedures. After the procedures, 1266 (9.76%) biopsies were associated with voiding difficulty; 148 (1.14%) biopsies, with significant bleeding; and 855 (6.59%) biopsies, with infection that required treatment. The prostate cancer diagnosis rate was 36.02%. The overall biopsy-related mortality rate within 30 days was 0.25%, and the postbiopsy sepsis-related mortality rate was 0.13%. Age, diagnosis of cancer, hospitalization, and CCI value ≥ 1 were all significant factors in univariate analysis and multivariate analysis for postbiopsy voiding difficulty and severe infection. A diagnosis of cancer and a CCI value ≥ 2 were significant factors for significant bleeding after biopsy. Patients diagnosed as having prostate cancer had fewer bleeding complications after biopsy. CONCLUSION: The most frequent complication was postbiopsy voiding difficulty, followed by infection that required treatment and significant bleeding. The sepsis-related mortality rate was 0.13%. Significant risk factors for postbiopsy complications included age, diagnosis of prostate cancer, hospitalization, and the CCI value.

Robot-assisted laparoscopic excision of a retroperitoneal paracaval tumor.

During the past few years, robotic surgical systems have been rapidly developed. The progress and advantages of these systems include three-dimensional vision and enhanced ergonomics. These advantages have helped a new generation of minimally invasive surgery to evolve. The da Vinci Surgical System seems to greatly resolve problems (e.g., wide exposure and retraction of peritoneal organs) that are confronted by traditional laparoscopic surgeries for retroperitoneal tumors that are near great vessels. There have been few reported cases concerning laparoscopic excision of retroperitoneal tumors situated between the inferior vena cava, the right renal vessel, and the kidney. We report the use of a robotic surgical system for this type of treatment. A 54-year-old female patient had a hypoechoic lesion near the inferior vena cava and superior to the right renal vessels. It was incidentally found by ultrasound during a health check-up examination. The computed tomography (CT) scan revealed a heterogeneous contrast-enhanced retroperitoneal mass approximately 4.4 cm medial to the right kidney with the inferior vena cava slightly deviated to the left. Robot-assisted laparoscopic excision of the retroperitoneal tumor was performed on October 15, 2010 with an operation time of 135 minutes and an estimated blood loss of less than 30 mL. The J-Vac drainage tube was removed on postoperative Day 3, and the patient was discharged in a stable condition the following day. The pathology of the tumor was retroperitoneal schwannoma. A re-evaluation was arranged postoperatively for the 15-month ambulatory visit. No local recurrence or distal metastasis was present.

The role of hormones on semen parameters in patients with idiopathic or varicocele-related oligoasthenoteratozoospermia (OAT) syndrome.

BACKGROUND: Oligoasthenoteratozoospermia (OAT) syndrome is the most frequently seen phenotype in male infertility. Spermatogenesis relies closely on hormone regulation. The aim of this study was to assess the correlation between hormone profile and semen parameters in infertile men with idiopathic or varicocele-related OAT syndrome. We tried to illustrate the correlative factors for better semen parameters in these patients. METHODS: A total of 96 patients with idiopathic or varicocele-related OAT were included for assessment. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), prolactin (PRL), and the combinative ratios of these hormones, such as T/E2, T/FSH, T/LH, T/(FSH × LH), PRL × T/FSH, PRL × T/LH, PRL × T/(FSH × LH), were compared individually with sperm parameters. The parameters included sperm concentration, total sperm count (TC), percent motile sperm count, percent normal sperm count, total motile sperm count (TMC), total normal sperm count (TNC), and total motile normal sperm count (TMNC). RESULTS: T correlated well with percent normal sperm count (p = 0.031). PRL positively correlated with sperm concentration (p = 0.019), TMC (p < 0.001), TNC (p = 0.003), and TMNC (p < 0.001). In hormonal combinative ratios, T/FSH, T/LH, T/(FSH × LH), PRL × T/FSH, PRL × T/LH, and PRL × T/(FSH × LH) all showed significant correlations to concentration and count-related parameters including TC, TMC, TNC, and TMNC. CONCLUSION: For patients with OAT syndrome, T, PRL, T/FSH, T/LH, T/(FSH × LH), PRL × T/FSH, PRL × T/LH, and PRL × T/(FSH × LH) may be used as predictive markers for better semen quality. This investigation could be a catalyst for future studies on the extent to which manipulating the hormonal combinative ratios can affect the quality of spermatogenesis in infertile males with OAT syndrome.