Comparison of Quality of Life and Injection Site Reactions After Switching from Degarelix 80 mg to 480 mg in Advanced Prostate Cancer: A Prospective Trial.

BACKGROUND/AIM: Degarelix has been widely used for prostate cancer; however, injection site reactions (ISRs) can be a clinical issue. We assessed differences in ISR intensity and patient quality of life (QOL) between degarelix 80 mg and 480 mg, a three-month formulation launched in 2020 in Japan. PATIENTS AND METHODS: We prospectively analyzed 25 patients with advanced prostate cancer. ISR intensity and patient QOL were evaluated before and after switching from degarelix 80 mg to 480 mg. A visual analogue scale (VAS) and faces rating scale (FRS) were applied to assess the ISRs. We applied a rating format from the M. D. Anderson Symptom Inventory (MDASI) to assess patient QOL. RESULTS: For degarelix 80 mg and a first dose of 480 mg, the incidence rate of ISRs was 84% and 92%, respectively (p=0.083). ISR pain on the third day after injection scored by VAS was 2.7±2.8 and 5.2±2.7, respectively (p<0.001). Other ISR findings such as redness, induration, swelling, warmth, and itching were significantly worse for degarelix 480 mg than for 80 mg. In the category of patient QOL, interference with activities of daily living such as general activity was significantly worse after degarelix 480 mg (p=0.003). However, 80% of patients were able to continue degarelix 480 mg during the nine months of follow-up. CONCLUSION: Degarelix 480 mg seems to exacerbate pain and other ISR findings, and to reduce patient QOL, compared with degarelix 80 mg. Optimal management of ISRs is essential to maintain patient QOL when using degarelix 480 mg.

Feasibility of Novel Technique of Flexible Cystoscopic En Bloc Snare Resection of Bladder Tumor: f-ESRBT.

Background: En bloc resection of bladder tumors (ERBT) has been used as a treatment option to improve pathologic diagnostic accuracy in non-muscle invasive bladder cancer. We report on the feasibility of a novel ERBT technique using an electrosurgical snare with flexible cystoscope: flexible cystoscopic En bloc Snare Resection of Bladder Tumor (f-ESRBT). Methods: We used the electrosurgical snare to resect a superficial bladder tumor after injection of 50% glucose in the submucosa at the tumor base. We collected each resected tumor with a basket catheter and coagulated the resected area with a coagulation electrode. A flexible cystoscope was used for all procedures. Results/Discussion: We performed 10 operations. Mean tumor size was 10.2 ± 7.3 mm and mean surgery time was 13.8 ± 6.8 minutes. All procedures were performed without complications. Results showed f-ESRBT to be simple and minimally invasive and to enable accurate pathologic diagnoses. Conclusion: f-ESRBT is a feasible treatment option for small and non-muscle invasive bladder cancer.

Percutaneous cryoablation versus partial nephrectomy for cT1b renal tumors: An inverse probability weight analysis.

PURPOSE: To investigate differential clinical outcomes in patients treated with partial nephrectomy (PN) vs. percutaneous cryoablation (PCA) for cT1b renal tumors. MATERIALS AND METHODS: We retrospectively analyzed the records of 119 patients who had undergone PN (n = 90) or PCA (n = 29) for cT1b renal tumors. Inverse probability weighting (IPW) was used for balancing patient demographics, including renal function and tumor complexity. Perioperative complications, renal function preservation rates, and oncological outcomes such as local recurrence-free, metastasis-free, cancer-specific, and overall survival were compared using IPW-adjusted restricted mean survival times (RMSTs). RESULTS: PCA was more likely to be selected for octogenarians (odds ratio: 11.4, 95% confidence interval [CI]: 3.33-45.1). During the median follow-up of 43 months in the PCA group and 36.5 months in the PN group, unablated local residue or local recurrence was noted in 6 patients in the PCA group and local recurrence was noted in 4 patients in the PN groups. Of the 6 patients in the PCA group, 4 underwent salvage PCA, and local control had been achieved at the last visit. In the IPW-adjusted population, PCA had significantly worse local recurrence-free survival compared with PN (IPW-adjusted RMST difference: -22.7 months, 95% CI: -45.3 to -0.4, P = 0.046). IPW-adjusted RMST for metastasis-free survival (P = 0.23), cancer-specific survival (P = 0.77), and overall survival (P = 0.11) did not differ between PCA and PN. In addition, PN was not a predictor for local control failure at the last visit (odds ratio: 0.30, 95%CI: 0.05-1.29). There were no statistically significant differences between PN and PCA in renal function preservation or overall/severe complication rates. CONCLUSIONS: In patients with cT1b renal tumor, although the local recurrence rate is higher for PCA than for PN, PCA provides comparable distant oncologic outcomes. PCA can be an alternative treatment option for elderly, comorbid patients, even those with cT1b renal tumors.

Laparoscopic partial nephrectomy for the horseshoe kidney with indocyanine green fluorescence guidance under the modified supine position.

Introduction: Owing to the complexity of their blood supply, renal tumors in horseshoe kidneys are sometimes technically challenging to resect through laparoscopic procedures. Case presentation: A 75-year-old man presented with a 3-cm lower-pole mass in the right moiety of the horseshoe kidney. Indocyanine green administration allowed for the identification of the tumor's feeding artery, which was selectively clamped to perform laparoscopic partial nephrectomy. During the procedure, the patient was positioned in the modified supine position (30° semi-lateral position), which enabled us to approach the branch of the left renal artery. Postoperative pathologic examination of the resected mass confirmed the diagnosis of pT1a clear cell renal cell carcinoma with negative surgical margins. Conclusion: Our novel laparoscopic approach with indocyanine green fluorescence in the modified supine position facilitates the identification of and access to the tumor's feeding artery. This technique is advantageous for laparoscopic partial nephrectomy in patients with horseshoe kidney.

Does castration status affect docetaxel-related adverse events? :Identification of risk factors for docetaxel-related adverse events in metastatic prostate cancer.

BACKGROUND: Docetaxel-related adverse events (AEs) such as neutropenia and febrile neutropenia (FN) can be life-threatening. A previous in vivo study raised the hypothesis that the castration status affects the rate of hematologic AEs. We aimed to investigate the impact of castration status on the incidence of docetaxel-related AE in metastatic prostate cancer (mPCa) patients. METHODS: We retrospectively analyzed the records of 265 mPCa patients treated with docetaxel, comprising 92 patients with metastatic hormone-sensitive prostate cancer (mHSPC) and 173 patients with metastatic castration-resistant prostate cancer (mCRPC) between January 2015 and December 2021. Common terminology Criteria for Adverse Events (CTCAE) was applied to evaluate AEs. We analyzed the differential incidences between mHSPC and mCRPC, and risk factors of hematologic and nonhematologic AEs using a logistic regression model. RESULTS: The rate of patients who received primary prophylaxis against neutropenia was higher in those with the mHSPC compared with those with the mCRPC (7.5% vs. 33%, p < 0.001). Among the patients without primary prophylaxis, incidence rates of severe neutropenia (CTCAE ≥ Grade3) and FN were 89% and 16% in patients with mCRPC compared to 81% and 18% in those with mHSPC. Logistic regression analysis revealed that age ≥ 75 years and failure to provide primary prophylaxis were independent risk factors of severe neutropenia (odds ratio [OR]: 2.39, 95% confidential interval [CI]: 1.10-5.18 and OR: 15.8, 95% CI: 7.23-34.6, respectively). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≧ 1 was an independent risk factor of FN (OR: 2.26, 95% CI: 1.13-4.54). Castration status (mHSPC vs. mCRPC) was not associated with the risks of severe neutropenia and FN. CONCLUSIONS: Castration status did not affect the risk of severe neutropenia or FN in mPCa patients treated with docetaxel regardless of the disease state. Failure to provide primary prophylaxis and advanced patient age are independent risk factors of severe neutropenia; while patients with poor PS are more likely to develop FN. These findings may help guide the clinical decision-making for proper candidate selection of docetaxel treatment.

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although prostate cancer is a very common form of malignancy in men, the clinical significance of androgen deprivation therapy (ADT) with abiraterone acetate versus the nonsteroidal antiandrogen bicalutamide has not yet been verified in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). The present study was designed to initiate this verification in real-world Japanese clinical practice. METHODS: We retrospectively analyzed the records of 312 patients with high-risk mHSPC based on LATITUDE criteria and had received ADT with bicalutamide (n = 212) or abiraterone acetate (n = 100) between September 2015 and December 2020. Bicalutamide was given at 80 mg daily and abiraterone was given at 1000 mg daily as four 250-mg tablets plus prednisolone (5-10 mg daily). Overall survival (OS), cancer-specific survival (CSS), and time to castration-resistant prostate cancer (CRPC) were compared. The prognostic factor for time to CRPC was analyzed by Cox proportional hazard model. RESULTS: Patients in the bicalutamide group were older, and more of them had poor performance status (≧2), than in the abiraterone group. Impaired liver function was noted in 2% of the bicalutamide group and 16% of the abiraterone group (p < 0.001). Median follow-up was 22.5 months for bicalutamide and 17 months for abiraterone (p < 0.001). Two-year OS and CSS for bicalutamide versus abiraterone was 77.8% versus 79.5% (p = 0.793) and 81.1% versus 82.5% (p = 0.698), respectively. Median time to CRPC was significantly longer in the abiraterone group than in the bicalutamide group (NA vs. 13 months, p < 0.001). In multivariate analysis, Gleason score ≧9, high alkaline phosphatase, high lactate dehydrogenase, liver metastasis, and bicalutamide were independent prognostic risk factors for time to CRPC. Abiraterone prolonged the time to CRPC in patients with each of these prognostic factors. CONCLUSIONS: Despite limitations regarding the time-dependent bias, ADT with abiraterone acetate significantly prolonged the time to CRPC compared to bicalutamide in patients with high-risk mHSPC. However, further study with longer follow-up is needed.

The prognostic value of the preoperative lung immune prognostic index in patients with urothelial bladder cancer undergoing radical cystectomy.

BACKGROUND: The lung immune prognostic index (LIPI) predicts the prognosis of patients with advanced non-small-cell lung cancer and is a prognostic biomarker for renal cell carcinoma and melanoma; however, no study has evaluated its potential as a preoperative biomarker for patients with bladder cancer (BC). We investigated the LIPI as a preoperative prognostic biomarker in patients undergoing radical cystectomy. METHODS: We retrospectively analyzed the clinical records of 105 patients with BC who underwent radical cystectomy from January 2013 to June 2019. The LIPI was evaluated based on the preoperatively derived neutrophil-lymphocyte ratio and the lactate dehydrogenase levels. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and decision curve analysis (DCA) were performed to assess the disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. RESULTS: The patients were classified into the good, intermediate, and poor LIPI groups [71 (67.6%), 28 (26.7%), and 6 (5.7%) patients, respectively]. IPTW-adjusted Kaplan-Meier curve analyses showed that patients with intermediate to poor LIPI had worse DFS, CSS, and OS rates than those with good LIPI. The LIPI combined with pT3/4 and lymph node metastasis could better assess the prognosis of DFS at 24 months postoperatively by DCA. CONCLUSION: The preoperative LIPI can predict the prognosis of patients with BC undergoing radical cystectomy and has a better predictive ability when combined with pT3/4 and lymph node metastasis.

Clinical Significance of Horizontal and Vertical Margin of En Bloc Resection for Nonmuscle Invasive Bladder Cancer.

PURPOSE: The primary advantage of en bloc resection of bladder tumors is to provide better diagnostic accuracy. However, the clinical significance of horizontal and vertical margin has not been demonstrated. We evaluated the clinical importance of surgical margins in patients who underwent en bloc resection of bladder tumors. MATERIALS AND METHODS: We retrospectively analyzed the records of 140 consecutive patients who underwent en bloc resection of bladder tumors for nonmuscle invasive bladder cancer. We analyzed perioperative and oncological outcome, and compared patient demographics and recurrence-free survival for horizontal findings. The relationship between surgical margin and second transurethral resection outcome in pT1 bladder cancer was also analyzed. RESULTS: Mean tumor diameter was 17.2±9.8 mm. Pathological stages were 93 cases in pTa and 47 cases in pT1. Diagnostic rates for the horizontal and vertical margins were 63% and 99%, respectively. The rates of sessile, carcinoma in situ, high grade, and pT1 tumors were significantly higher in the horizontal margin positive group (41) than in the negative group (47). There was no significant difference in 2-year recurrence-free survival based on horizontal margin findings (negative: 72.4%, positive: 75.4%, p=0.87). A second transurethral resection was performed in 31 of the 47 pT1 patients; pT1 residue was seen only in vertical margin positive cases, and 5 pTa/pTis residues at the transurethral resection scar were seen in 15 horizontal margin positive patients. CONCLUSIONS: Horizontal margin positive findings were not associated with recurrence-free survival, but careful assessment is warranted regarding residue at the original site. A second transurethral resection should be considered in patients with horizontal and vertical margin positive pT1 bladder cancer.

Vertical Lamina Propria Invasion Diagnosed by En Bloc Transurethral Resection is a Significant Predictor of Progression for pT1 Bladder Cancer.

PURPOSE: T1 bladder cancer is characterized by high recurrence and aggressive progression. Muscularis mucosae invasion may be a prognostic factor for progression, but the limitations of conventional transurethral resection of bladder tumors make diagnosis difficult. We correlated degree of invasion with oncologic outcome and evaluated the utility of pathological diagnosis following en bloc resection of bladder tumors. MATERIALS AND METHODS: We retrospectively analyzed the records of 123 consecutive patients diagnosed with pT1 bladder cancer between November 2013 and December 2018. Transurethral resection was conducted in 91 patients, and en bloc resection in 32 patients. All specimens were analyzed for invasion depth and pT1 substaging (T1a/b: invasion above or into/beyond muscularis mucosae, pT1m/e: microinvasive or extensively invasive). Primary end points were prognostic values of pT1 substaging and invasion depth. The secondary end point was the pathological diagnostic utility of en bloc resection. RESULTS: Median followup was 23 months. Three-year progression-free survival rate differed significantly depending on muscularis mucosae invasion (pT1a: 97.3%, pT1b: 72.8%; p=0.003) and invasion depth from basal membrane (<2 mm: 90.6%, ≥2 mm: 77.9%; p=0.03). Multivariate analysis showed that sessile tumor and invasion depth from basal membrane ≥2 mm were independent prognostic factors for progression. Diagnostic rates for pT1a/b and invasion depth were 77.6% and 85.9%, respectively, with transurethral resection, but 100% and 100% with en bloc resection (p=0.01 and p=0.03). CONCLUSIONS: Vertical lamina propria invasion is predictive of progression in T1 bladder cancer, underlining the importance of accurately diagnosing the degree of vertical lamina propria invasion with en bloc resection.

Supine extraperitoneal laparoscopic nephroureterectomy without patient repositioning.

OBJECTIVE: To describe a novel technique allowing laparoscopic nephroureterectomy with bladder cuff excision and lymphadenectomy, in a complete supine position, without patient repositioning. METHODS: Between January 2016 and October 2018, 20 consecutive patients with upper urinary tract urothelial carcinoma underwent supine extraperitoneal laparoscopic nephroureterectomy. The patients were placed in the complete supine position. A 4-cm pararectal skin incision was made and the extraperitoneal space was developed. We used a unique port placement that permits complete access for nephroureterectomy, bladder cuff excision and concomitant lymphadenectomy. Operative parameters and pathological data were analyzed. RESULTS: The median age was 70 years (range 49-88 years), the mean operative time was 234 min (range 175-293 min) and the mean estimated blood loss was 67 mL (range 50-200 mL). There were no intraoperative complications, and no patients required transfusion or open conversion. The median number of removed lymph nodes was 10; only one patient had node metastasis. The total operative time and time for nephroureterectomy were significantly longer in the first 10 patients (first group) than in the second 10 patients (second group). Times required for bladder cuff excision and lymphadenectomy did not differ between the two groups. CONCLUSIONS: Our novel technique, which enables completion of the entire procedure of nephrouretectomy with bladder cuff excision and lymphadenectomy in the supine position without patient repositioning, is safe and minimizes operative time while maintaining oncological efficacy. We believe this approach might become a standard option for patients with upper urinary tract urothelial carcinoma.

Feasibility and accuracy of pathological diagnosis in en-bloc transurethral resection specimens versus conventional transurethral resection specimens of bladder tumour: evaluation with pT1 substaging by 10 pathologists.

AIMS: En-bloc transurethral resection (TUR) of bladder tumour (ERBT) is designed to provide more accurate pathological diagnosis of specimens than conventional TUR of bladder tumour (cTURBT). Some studies have reported that T1 bladder cancer substage could be a prognostic factor in assessing tumour progression, but such substaging has not been widely adopted because of problems with pathological diagnosis using cTURBT specimens. The aim of this study was to evaluate the possible advantages of en-bloc TUR specimens in T1 substaging following assessment by a panel of 10 pathologists. METHODS AND RESULTS: We assessed the substages in 123 patients (cTURBT, n = 91; ERBT, n = 32) who were diagnosed with pT1 bladder cancer. We randomly selected 10 ERBT specimens and 10 cTURBT specimens with cancer invasion areas equivalent to those of their corresponding ERBT specimens. Ten pathologists performed pT1 substaging for pT1a/b/c and pT1m/e in 20 patients (cTURBT, n = 10; ERBT, n = 10). We evaluated diagnostic times and rates of diagnostic concordance among these pathologists, comparing cTURBT and ERBT. The median diagnostic times per slide were 87.7 s [interquartile range (IQR) 71.9-109.2 s) for cTURBT and 54.7 s (IQR 46.0-59.6 s) for ERBT (P = 0.009). The rate of diagnostic concordance was significantly better for ERBT specimens. For pT1a/b/c, the median concordance rates were 50% for cTURBT and 80% for ERBT (P = 0.02); for pT1m/e, the median concordance rates were 70% for cTURBT and 90% for ERBT (P = 0.05). For pT1a/b/c, the average κ-values between the pathologist and the standard diagnosis were 0.04 for cTURBT and 0.47 for ERBT. CONCLUSIONS: The use of ERBT specimens shortened the diagnostic time and minimised interobserver variability for T1 substaging compared with the use of cTURBT specimens.

[A case of percutaneous BCG perfusion therapy for CIS of upper urinary tract CIS after radical cystectomy with ileal neobladder].

We report a case of percutaneous bacillus Calmette-Guérin (BCG) perfusion therapy for carcinoma in situ (CIS) of upper urinary tract after radical cystectomy with ileal neobladder. A 42-year-old man underwent radical cystectomy and ileal neobladder diversion due to the recurrence of CIS in prostatic urethra after transurethral resection of bladder tumor 3 times and 2 courses of intravesical BCG therapy. Final pathological findings showed the presence of CIS in the right distal ureteral margin. After the radical cystectomy, our diagnosis was CIS in the right residual ureter, because of positive urine cytology and negative radiographic findings in the upper urinary tract. We performed the percutaneous BCG perfusion therapy for CIS of the right upper urinary tract after the construction of the percutaneous nephrostomy by intentionally inducing hydronephrosis. No recurrence was found after 3 years of BCG perfusion therapy.