Cost-effectiveness of immune checkpoint inhibitors in treating metastatic urothelial cancer.

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients. Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab). The patients were divided into three different groups: receiving chemotherapy alone, receiving a combination of first-line ICI and chemotherapy (ICI combination therapy), and receiving chemotherapy as the first-line treatment followed by second-line ICI therapy (Subsequent ICI therapy). The primary endpoint was cost per life day, while lifetime medical costs and overall survival were also evaluated. Results: The 74 enrolled patients had a median age of 67.0 years, with 62.2% being male. Of these patients, 23 had received chemotherapy only, while the remaining patients had received combined therapy with ICI in either first-line or as subsequent agents (37 patients had ever received atezolizumab, 18 pembrolizumab, 1 Durvalumab, 1 Nivolumab, and 1 Avelumab separately.). Fifty-five patients (74.3%, 55/74) received cisplatin amongst all the patients who underwent chemotherapy. Median overall survival was 27.5 months (95% CI, 5.2-49.9) in the first-line ICI combination therapy group, and 8.9 months (95% CI, 7.1-10.8) in the chemotherapy only. Median overall survival for the subsequent ICI therapy group was not reached. The median lifetime cost after metastatic UC diagnosis was USD 31,221. The subsequent ICI therapy group had significantly higher costs when compared with the ICI combination therapy group (155.8 USD per day, [IQR 99.0 to 220.5] v 97.8 USD per day, [IQR 60.8 to 159.19], p = 0.026). Higher insurance reimbursement expenses for the subsequent ICI therapy group were observed when compared with the ICI combination therapy group. Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy.

Outcome benefits of upfront cytoreductive nephrectomy for patients with metastatic renal cell carcinoma: An analysis of the TriNetX database.

BACKGROUND: The role of upfront cytoreductive nephrectomy remains debatable in the present era of tyrosine kinase inhibitors and immune checkpoint inhibitors. Here, we aimed to evaluate the outcomes of metastatic renal cell carcinoma patients treated with upfront CN and modern systemic therapies. METHODS: Using the TriNetX network database, we identified patients, in the period from 2008 to 2022, who were diagnosed with metastatic renal cell carcinoma, receiving first-line systemic therapies with tyrosine kinase inhibitors or immune checkpoint inhibitors. Their overall survivals were evaluated using the Kaplan-Meier method as well as multivariable regressions. RESULTS: We identified 11,094 patients with metastatic renal cell carcinoma. Of them, 2,914 (43%) patients in the tyrosine kinase inhibitor cohort (n = 6,779), and 1,884 (43.7%) in the immune checkpoint inhibitors cohort (n = 4315) underwent upfront cytoreductive nephrectomy. Those receiving upfront cytoreductive nephrectomy showed survival advantages with either tyrosine kinase inhibitor (Hazard ratio 0.722, 95% Confidence interval 0.67-0.73, p<0.001) or immune checkpoint inhibitors (Hazard ratio 65.1, 95% Confidence interval 0.59-0.71, p<0.001). In multivariable analysis, upfront cytoreductive nephrectomy was a factor for improved OS in both cohorts: tyrosine kinase inhibitors (Hazard ratio 0.623, 95% Confidence interval 0.56-0.694, p<0.001) and immune checkpoint inhibitors cohort (Hazard ratio 0.688, 95% Confidence interval 0.607-0.779, p<0.001). CONCLUSIONS: Upfront cytoreductive nephrectomy was associated with an improved overall survival for patients with metastatic renal cell carcinoma receiving either first-line tyrosine kinase inhibitors or immune checkpoint inhibitors. Our results support a clinical role of upfront cytoreductive nephrectomy in the modern era.

Malfunction endostapler trapped on renal vein - Nightmare scenario for surgeon.

The utilization of endostapler devices has become standard practice for renal vein ligation during laparoscopic nephroureterectomy. While exceptionally rare, malfunctions can occur in these devices. In the video, we present a malfunctioning endostapler that became trapped on the renal vein. Fortunately, this catastrophic event was successfully managed without conversion to open surgery or massive blood loss and was recorded on video. We propose a structured management flow chart for addressing GIA malfunction, aiming to assist surgeons in navigating through this potentially life-threatening situation.

The impact of squamous cell transformation on the prognosis of patients treated with radical nephroureterectomy.

BACKGROUND: Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy. METHODS: We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses. RESULTS: The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS. CONCLUSIONS: SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE). MATERIALS AND METHODS: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test. RESULTS: Based on our research, ureter tumor, female, smoking history, age (< 70 years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR. CONCLUSION: Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients.

Nephroscope-assisted single trocar peritoneal dialysis catheter insertion improves catheter survival compared with laparoscopic technique: Ten-year experience of a single-center.

BACKGROUND: An ideal technique for peritoneal dialysis (PD) catheter insertion should provide a long-term functioning catheter until permanent renal replacement therapy becomes available. We developed a technique using the nephroscope-assisted single-trocar approach in 2011. In this study, we report the outcomes, learning curve analysis and cost-effectiveness analysisof the nephroscopic approach compared with the traditional laparoscopic approach. METHOD: Between January 2005 and December 2020, we retrospectively reviewed 511 patients who received PD catheter insertions using the laparoscopic or nephroscopic approach. We compared the baseline characteristics of the patients, surgical outcomes, and complications of the two groups. We further analyzed the nephroscopic group to determine the cost-effectiveness analysis, learning curve and the complication frequency between the learning and mastery periods of the nephroscopic approach. RESULTS: A total of 208 patients underwent laparoscopic PD catheter insertion, whereas 303 patients received nephroscopic surgery. The median catheter survival in the nephroscopic group is significantly longer (43.1 vs. 60.5 months, p = 0.019). The incidence of peritonitis (29.3% vs.20.8%, p = 0.035) and exit site infection (12.5% vs. 6.6%, p = 0.019) were significantly lower in the nephroscopic group. The cost-effectiveness analysis showed a medical expense reduction of 16000 USD annually by using the nephroscopic technique. There was no difference in the frequency of surgical complications between the learning and mastery phases when examining the learning curve analysis for the nephroscopic technique. CONCLUSIONS: Compared with the traditional laparoscopic approach, the nephroscopic technique effectively prolonged catheter survival and reduces health care cost by reducing infectious complications. The low complication rate during the learning phase of surgery makes the procedure safe for patients and surgeons.

The impacts of MACC1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

Urothelial cell carcinoma (UCC) is a common malignancy of the urinary tract in Taiwan. Metastasis-Associated in Colon Cancer 1 (MACC1), a newly identified oncogene and regulator of the HGF/Met signaling pathway, has been shown to play a critical role in the development and progression of several types of cancer. Our study aims to investigate the impact of MACC1 gene polymorphisms on the clinicopathological features of patients with UCC. In this study, we included a total of 719 patients with UCC and 719 healthy controls. The genotyping of five MACC1 gene polymorphisms (rs1990172, rs975263, rs3095007, rs4721888, and rs3735615) was performed using real-time PCR with TaqMan assays. Our findings indicate that urothelial cancer patients with MACC1 rs3095007 A allele had a decreased risk of >T2 stage [Odds ratio (OR)=0.619, 95% CI=0.394-0.971, p=0.036] and lymph node invasion (OR=0.448, 95% CI=0.201-0.998, p=0.044). Additionally, these individuals were associated with longer relapse-free survival (p=0.007) and overall survival (p=0.028). In conclusion, our findings demonstrate that urothelial cancer patients with MACC1 (rs3095007) CA and AA genotypes have a lower risk of advanced T stage and lymph node metastasis. Additionally, these genotypes were associated with longer relapse-free survival and overall survival, highlighting the potential of these biomarkers as predictors of UCC prognosis.

Real world treatment sequences and outcomes for metastatic renal cell carcinoma.

OBJECTIVES: The treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting. MATERIALS AND METHODS: We enrolled patients with metastatic renal cell carcinomawho received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinibbetween January2009 and May 2023 on the database of TriNetX network. Overall survival, time on treatment and time to next treatment were evaluated using Kaplan-Meiermethod. RESULTS: Totally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median time on treatment was 2.5 months for the tyrosine kinase inhibitor monotherapy cohort, 5.4 months for the ipilimumab plus nivolumab cohort, and 8.3 months for the pembrolizumab plus axitinib cohort. Median time to next treatment was 16.6 months for both the tyrosine kinase inhibitor monotherapy and ipilimumab plus nivolumab cohorts, and 22.1 months for the pembrolizumab plus axitinib cohort. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7monthsfor the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (log-rank p = 0.0168) in overall survival, but not the case in the ipilimumab plus nivolumab cohort. CONCLUSION: There was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts, while patients in the ipilimumab plus nivolumab cohort had more distant metastases and comorbidities.

Prognostic Factors of Extramammary Paget's Disease: A Retrospective Study at a Medical Center in Taiwan.

BACKGROUND/AIM: Extramammary Paget's disease (EMPD) is a rare, slow growing intra-epidermal malignant neoplasm that arises in areas rich in apocrine glands. Several common sites of occurrence have been reported, including the vulva, perianal region, perineum, and scrotum. Most relevant studies rely on small data bases. Our objective was to evaluate prognostic factors of EMPD patients at a single medical center. PATIENTS AND METHODS: We retrospectively analyzed 19 patients (8 males, 11 females) diagnosed with genital EMPD who were treated at the Taichung Veterans General Hospital between 2006/04 and 2022/08. Collected information included tumor location, margin condition in the case of surgical resection, recurrence rate, recurrence management, accompanied gastrointestinal malignancy, treatment details and survival data. RESULTS: Among 19 cases, 4 with initial margin being positive, and 3 received second surgery (one refused surgery and another expired within a year). Tumor recurrence was found in 7 cases, with 6 of them later receiving second surgery, and the remaining one received radiation therapy. Median DFS was 7.57 years. During the 15-year follow-up, 2 patients expired. Overall survival rate was 87.5%. Among all factors we had analyzed, only those accompanied with GI tract malignancy had significantly worse survival rate (p=0.018). Frozen sections taken at surgical margin during surgery significantly reduced cancer recurrence rate (p=0.45). Permanent pathology margins appeared to affect the recurrence rate, but that was not significant when comparing with intraoperative frozen sections. CONCLUSION: Local wide excision with skin flap reconstruction remains the major treatment option for genital EMPD. Following the standard-of-care procedure, the overall patient outcome was excellent. Among factors potentially associated with recurrence rate, intraoperative frozen biopsy was the most significant one. Performing intraoperative frozen biopsy is essential for recurrence-free rate elevation.

Influence of Surgical Complications on Outcomes in Kidney Transplantation Patients.

BACKGROUND/AIM: With the increasing use of marginal donors, it is important to identify factors for outcomes in kidney transplantation. The aim of the present study was to evaluate the influence of surgical complications for graft survival after kidney transplantation and identify risk factors for surgical complications. PATIENTS AND METHODS: We performed a retrospective cohort study by chart review of patients who underwent kidney transplantation at the Taichung Veterans General Hospital in the period from 2007 to 2018. RESULTS: Of the 433 patients who underwent kidney transplantation, 57 experienced surgical complications with an occurrence rate of 13.2%. The most common complications were vascular complications (n=31; 7.2%), followed by urologic (n=9; 2%) and wound (n=9; 2%) complications. From univariate analyses, risk factors for surgical complications were cold ischemia time, blood loss, operation time, number of vascular anastomoses and year of operation. From univariate and multivariate analyses, operation time was associated to surgical complications. Patients with surgical complications experienced worse both one-year and five-year death-censored graft and patient survival. CONCLUSION: Surgical complications were associated with higher risk of death-censored graft failure and mortality. Cold ischemia time, blood loss, operation time, number of vascular anastomoses and year of operation were risk factors for surgical complications. Efforts should aim to minimize surgical complications to improve both graft and patient survival.

Prostate­specific antigen density and preoperative MRI findings as predictors of biochemical recurrence in high­risk and very high­risk prostate cancer.

Patients with high-risk prostate cancer after prostatectomy have a particularly high chance of being diagnosed with biochemical recurrence (BCR). Patients with BCR have a greater risk of disease progression and mortality. The present retrospective observational study aimed to clarify the risk factors for the BCR of prostate cancer after radical prostatectomy in patients with high-risk and very high-risk prostate cancer. Patients diagnosed with prostate cancer who received radical prostatectomy in a single center from January 2009 to June 2020 were included in the study. Data from medical records were reviewed and the patients were followed up for ≥6 years. The primary outcome was BCR within 1 year after surgery. A total of 307 patients were included, with 187 in the high-risk group and 120 in the very high-risk group as classified by the National Comprehensive Cancer Network (NCCN) guidelines. Patients in the very high-risk group had a lower BCR-free survival rate compared with those in the high-risk group, with a high risk of BCR even if their PSA levels were initially undetectable after prostatectomy, and a high risk of postoperatively detectable PSA. In patients with undetectable PSA after prostatectomy, BCR was associated with the initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1). Postoperatively detectable PSA was associated with pathologic stage (T3bN0M0 and any N1) In conclusion, preoperative MRI imaging stage and PSA density are predictors for short-term BCR after prostatectomy. NCCN-defined high-risk patients with a high initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1) had a higher risk of BCR when compared with other patients with undetectable PSA, while those with pathologic stage (T3bN0M0 or any N1) displayed a higher risk of postoperatively detectable PSA. These findings may help urologists to identify patients for whom active therapeutic protocols are necessary.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.

Metastasectomy Improves Overall Survival in Metastatic Renal Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND/AIM: The use of complete metastasectomy for treating metastatic renal cell carcinoma (mRCC) has been shown to improve survival outcomes in the era of tyrosine kinase inhibitors (TKIs). However, its effectiveness in combination with immune checkpoint inhibitors (ICIs) remains unclear. Therefore, the objective of the study was to elucidate the impact of metastasectomy in patients with mRCC who received both TKIs or ICIs. PATIENTS AND METHODS: A total of 157 patients diagnosed with metastatic renal cell carcinoma (mRCC) between 2006 and 2018 in Taichung Veterans General Hospital were included in the study. Patients were divided into two groups: the non-metastasectomy group (n=89) and the metastasectomy group (n=68). Kaplan-Meier analyses and Cox proportional hazards models were employed to evaluate the impact of metastasectomy and other risk factors on overall survival (OS). RESULTS: Among patients who underwent metastasectomy, 62 patients (91.18%) underwent metastasectomy for more than 50% of their metastatic sites, and 42 patients (61.76%) received complete metastasectomy. The median overall survival was 55.75 months in the metastasectomy group, which was significantly longer than the 15.14 months observed in the non-metastasectomy group (p<0.001). Multivariate regression analysis revealed that metastasectomy had a significant impact on overall survival [hazard ratio (HR)=0.42, 95% confidence interval (CI)=0.26-0.67, p<0.001]. Additionally, performance status and lactate dehydrogenase were identified as independent predictors for overall survival. CONCLUSION: Combination of metastasectomy with systemic therapy was shown to improve overall survival in patients with mRCC. Therefore, this modality may be considered as a viable option for patients who are fit for surgical intervention and are undergoing treatment with either TKIs or ICIs.

Risk analysis of subsequent therapies after first-line chemotherapy in advanced testicular cancer patients.

BACKGROUND: Testicular cancer is the most common solid cancer diagnosed among young men. Despite good response to chemotherapy and a high survival rate, subsequent salvage therapies may still be required for some patients in advanced stages. The predictive and prognostic markers are crucial unmet needs. METHODS: We retrospectively analyzed advanced testicular cancer patients who had received first-line chemotherapy between January 2002 and December 2020. The associations between baseline characteristics and clinical outcomes were evaluated. RESULTS: Of the 68 included patients, the median age was 29 years. Among them, 40 patients received only first-line chemotherapy while the remaining 28 received subsequent chemotherapy or surgeries. Data reveal that 82.5% (33/40) of the patients in the chemotherapy-only group were recorded as a good prognostic risk using the International Germ Cell Cancer Collaborative Group classification when compared with 35.7% (10/28) in the second-line therapy group. In the chemotherapy-only group, 53.8% of patients were presented with lymph node metastasis compared with 78.6% in the second-line therapy group ( p = 0.068). Fifteen percent of patients (6/40) were recorded as S stage 2-3 in the chemotherapy-only group, whereas 85.2% (23/28) were recorded as such in the second-line therapy group ( p < 0.001). The 5-year overall survival estimation was 92.9% in the chemotherapy-only group and 77.3% in the second-line therapy group. Univariate analysis for overall survival revealed that those patients at the S 2-3 stage and those receiving second-line therapies showed a trend of having an increased death risk (hazard ratio [HR] = 8.26, 95% confidence interval (CI), 0.99-68.67, p = 0.051; HR = 7.76, 95% CI, 0.93-64.99, p = 0.059, respectively). The S 2-3 stage was also independently associated with the risk of subsequent therapy (HR = 33.13; 95% CI, 2.55-430.64, p = 0.007). CONCLUSION: Our real-world data show the predictive role of serum tumor marker stage 2-3 to be associated with any subsequent therapies after first-line chemotherapy. This can facilitate clinical decision making during the testicular cancer treatment process.

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

Objectives: To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC). Patients and methods: This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage. Results: 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p< 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p<0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34). Conclusion: Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.

Complete Cycles of Radium-223 Improve Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer: A Retrospective Study.

BACKGROUND/AIM: The aim of this study was to investigate whether complete cycles of Radium-223 (Ra-223) improved survival in patients with metastatic castration resistant prostate cancer (mCRPC). PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with Ra-223 at Taichung Veterans General hospital. Patient and disease characteristics, laboratory results, number of bone metastases, mCRPC treatment sequence, Ra-223 treatment cycles and survival outcomes were collected. Overall survival and progression-free survival (PFS) were analyzed with Kaplan-Meier analysis. Uni- and multivariate analysis was used to identify clinical-radiologic factors that influence outcomes. RESULTS: From October 2016 to December 2020, 42 patients with mCRPC were enrolled. Twenty-three patients received <4 cycles of Ra-223 for mCRPC and 19 patients received 5-6 cycles. The median PSA progression free survival was 2.07 months in the <4 cycles group, compared to 3.93 months in the 5-6 cycles group (log rank p=0.006). The median overall survival was 3.93 months in the <4 cycles group, compared to 28.5 months in the 5-6 cycles group (log rank p<0.001). In the multivariate model, the course number of Ra-223 and pre-treatment alkaline phosphatase (ALP) levels were independent risk factors for overall survival. CONCLUSION: Patients who complete 5-6 cycles of Ra-223 had significantly better overall survival than those who didn't. Patients with a lower pre-treatment ALP were more likely to benefit from Ra-223 treatment.

Geriatric nutritional risk index as a prognostic marker for patients with upper tract urothelial carcinoma receiving radical nephroureterectomy.

To investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with upper tract urothelial cell carcinoma (UTUC) receiving radical nephroureterectomy (RNU). Between January 2001 and December 2015, we enrolled 488 patients with UTUC underwent RNU in Taichung Veterans General Hospital. GNRI before radical surgery was calculated based on serum albumin level and body mass index. The malnutritional status was defined as GNRI < 92.0. Using Kaplan-Meier analyses and Cox proportional hazards models to analyze the risk factors on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). 386 patients were categorized as normal nutritional status (GNRI ≥ 92) and 102 patients as malnutritional status (GNRI < 92). We used the receiver operating characteristic (ROC) curve for determined the association between GNRI and OS, with area under the curve (AUC) being 0.69. The 5-year survival rate of DFS, CSS and OS were 48.6%, 80.5% and 80.5% in the normal nutritional group and 28.0%, 53.2% and 40% in the malnutritional group. Using the multivariate analysis, malnutritional status was found as an independent risk factor for OS (hazard ratio [HR] = 3.94, 95% confidence interval [CI] 2.70-5.74), together with age (HR = 1.04, 95% CI 1.02-1.06), surgical margin positive (HR = 1.78, 95% CI 1.13-2.82), pathological T3 (HR = 2.54, 95% CI 1.53-4.21), pathological T4 (HR = 6.75, 95% CI 3.17-14.37) and lymphovascular invasion (HR = 1.81, 95% CI 1.16-2.81). We also found GNRI index as independent risk factor in DFS (HR = 1.90, 95% CI 1.42-2.54) and CSS (HR = 5.42, 95% CI 3.24-9.06). Preoperative malnutritional status with low GNRI is an independent marker in predicting DFS, CSS and OS in UTUC patients underwent RNU.

Conventional androgen deprivation therapy is associated with an increased risk of fracture in advanced prostate cancer, a nationwide population-based study.

PURPOSE: Androgen deprivation therapy (ADT) is the standard of care in advanced prostate cancer. We conducted a Taiwan National Health Insurance Research Database (NHIRD) study to evaluate the association between ADT and fracture risk in patient with prostate cancer in Taiwan. METHODS: Between 2001 and 2008, data from the Taiwan NHIRD was collected. We separated newly diagnosed prostate cancer patients into four groups: the injection of gonadotropin-releasing hormone agonists and antagonists group, the orchiectomy group, the oral antiandorgens group and the radical prostatectomy only group. A non-cancer matched control group was also assigned for comparison. T tests, chi-squared tests, multivariate Cox proportional hazard regression were performed. A subsequent fracture event was defined according to the appropriate diagnosis codes (ICD9-CM 800-829) with hospitalization. Patients with fracture before their diagnosis with prostate cancer were excluded. RESULTS: Overall, 22517 newly diagnosed patients with prostate cancer were enrolled in the study. After exclusion criteria were applied, 13321 patients were separated into the injection group (5020 subjects), the orchiectomy group (1193 subjects), the oral group (6059 subjects) and the radical prostatectomy only group (1049 subjects). The mean age of the overall study population was 74.4 years. Multi-variant analysis disclosed a significantly increased risk of fracture in the injection group, the orchiectomy group, and the oral group (hazard ratio [HR] = 1.55, 95%, confidence interval [CI] 1.36 to 1.76, p<0.001, HR = 1.95, 95%, CI 1.61 to 2.37, p<0.001, HR = 1.37, 95%, CI 1.22 to 1.53, p<0.001, respectively). In contrast, a significantly decreased fracture risk was noted in the radical prostatectomy only group (HR = 0.51, 95%, CI 0.35 to 0.74, p = 0.001). Patients receiving osteoporosis medication had a significantly decreased fracture risk (HR = 0.26, 95%, CI 0.19-0.37, p<0.001). CONCLUSIONS: ADT is associated with an increased risk of fracture. For patients receiving long-term prostate cancer castration therapy, doctors should always keep this complication in mind and arrange proper monitoring and provide timely osteoporosis medication.

Risk Analysis of Prostate Cancer Development Following Five-alpha Reductase Inhibitor Treatment for Benign Prostate Hyperplasia.

BACKGROUND/AIM: The clinical hazard of prostate cancer development after five-alpha reductase inhibitors (5ARI) treatment among benign prostate hyperplasia (BPH) patients is still controversial. The aim of this study was to evaluate the epidemiological features of BPH patients treated in a single institute to identify risk factors associated with prostate cancer development. PATIENTS AND METHODS: We retrospectively analyzed patients who were diagnosed with BPH and received alpha blockers (AB) only or 5ARI between January 2007 and December 2012 and followed up until death or December 2020. The primary study outcome was prostate cancer and high-grade prostate cancer. RESULTS: Of the 5,122 included patients, 14.9% (762/5,122) received 5ARI during their BPH treatment. The median age, initial prostate specific antigen (PSA) levels and the PSA change were significantly higher in the 5ARI group compared to those of the AB group. The prostate cancer diagnosis rate was higher in the 5ARI group, and the percentage of high-grade prostate cancer was not different between the two groups. In total, 1,715 (33.5%) patients were recorded dead, and the median follow-up period was longer in the 5ARI group. In Cox regression analysis, only age and initial PSA levels were significantly associated with prostate cancer. Late PSA was the only independent factor associated with high-grade prostate cancer development. CONCLUSION: Our real-world data revealed that age, initial PSA, and late PSA levels were associated with prostate cancer and high-grade prostate cancer diagnosis among BPH patients. Furthermore, 5ARI use had no effect on prostate cancer patient survival. However, PSA assessment during follow-up is still required in our institutional practice to avoid delayed diagnosis.

The prognostic impact of lymph node dissection for clinically node-negative upper urinary tract urothelial carcinoma in patients who are treated with radical nephroureterectomy.

BACKGROUND: To evaluate the prognostic impact of lymph node dissection (LND) in patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision (BCE) for clinically node-negative (cN0) upper urinary tract urothelial carcinoma (UTUC). METHODS: We retrospectively enrolled 520 patients with cN0 UTUC in a single tertiary referral center from 2000 to 2015. The patients were divided into three groups: patients with and without pathologically proved lymph node metastasis (pN1-3 and pN0, respectively) and patients without LND (pNx). We analyzed associations between overall survival (OS)/ disease-free survival (DFS)/ cancer-specific survival (CSS) and clinical characteristics. RESULTS: The patients were divided into three groups (pN1-3, pN0 and pNx with 20, 303, and 197 patients, respectively). OS/DFS/CSS in the pN1-3 group were significantly worse (all p<0.001) compared with the pN0 group. However, there were no significant differences between the pNx and pN0 groups. In the multivariate analyses, CSS was only affected by age [(hazard ratio (HR) = 1.03, p = 0.008]), positive surgical margin (HR = 3.38, p<0.001) and pathological T3-4 stages (HR = 4.07, p<0.001). In the subgroup analyses for patients with LND, locally advanced disease (pT3 and pT4) had significantly more metastases [T3-4: 13.91% (16/115) vs. T0-2: 1.92% (4/208), p<0.001]. CONCLUSIONS: In the pN0 group, LND for cN0 UTUC did not show therapeutic benefits in terms of DFS, CSS, and OS. However, LND with RNU allowed optimal tumor staging, through patients still had a poor prognosis. Clinically occult LN metastases were found in 6.2% of our patients.