Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry.

BACKGROUND: To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). PATIENTS AND METHODS: We queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression were fitted to elucidate predictors of outcomes. RESULTS: Total 3902 patients (high CRP n = 1266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, P < .001), ccRCC (HR 2.69, P < .001), chRCC (HR 3.99, P < .001), pRCC (HR 1.76, P = .009) and vhRCC (HR 2.97, P =.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, P < .001), chRCC (HR 6.16, P = .003) and pRCC (HR 2.29, P = .011), while in vhRCC was not (P = .27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, P = .013), while in chRCC (P = .33), pRCC (P = .34) and vhRCC (P = .52) was not. On multivariable logistic regression CRP was a predictor of pRCC (OR 1.003, P = .002), while decreasing CRP was associated with benign tumors (OR 0.994, P = .048). CONCLUSION: Elevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non-vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.

[A Case of Advanced Gastric Cancer Treated with Conversion Surgery followed by Nivolumab Combination Chemotherapy].

The use of nivolumab as first-line therapy for unresectable advanced gastric cancer has now become a standard practice, and its efficacy has been established. This is the first report of a patient with advanced gastric cancer who underwent conversion surgery after first-line nivolumab combination chemotherapy. The patient was a 58-year-old woman. Her medical history included hypertension and dyslipidemia. She had advanced gastric cancer with extensive lymph node metastasis in the left supraclavicular fossa and around the abdominal aorta. After confirming the HER2-negative status and the PD-L1 CPS score to be ≥5, nivolumab was administered in combination with chemotherapy. After the treatment, she underwent a total gastrectomy with D2 dissection, combined splenectomy and pancreatic tail resection for adhesions, and para-aortic lymph node sampling as a conversion surgery. There was no obvious cancerous remnant in the resected specimen, and the pathological response was Grade 3. The patient was alive and recurrence-free at 4 months postoperatively.

Stepwise algorithm using computed tomography and magnetic resonance imaging for differential diagnosis of fat-poor angiomyolipoma in small renal masses: A prospective validation study.

OBJECTIVES: To validate the diagnostic accuracy of a stepwise algorithm to differentiate fat-poor angiomyolipoma (fp-AML) from renal cancer in small renal masses (SRMs). METHODS: We prospectively enrolled 223 patients with solid renal masses <4 cm and no visible fat on unenhanced computed tomography (CT). Patients were assessed using an algorithm that utilized the dynamic CT and MRI findings in a stepwise manner. The diagnostic accuracy of the algorithm was evaluated in patients whose histology was confirmed through surgery or biopsy. The clinical course of the patients was further analyzed. RESULTS: The algorithm classified 151 (68%)/42 (19%)/30 (13%) patients into low/intermediate/high AML probability groups, respectively. Pathological diagnosis was made for 183 patients, including 10 (5.5%) with fp-AML. Of these, 135 (74%)/36 (20%)/12 (6.6%) were classified into the low/intermediate/high AML probability groups, and each group included 1 (0.7%)/3 (8.3%)/6 (50%) fp-AMLs, respectively, leading to the area under the curve for predicting AML of 0.889. Surgery was commonly opted in the low and intermediate AML probability groups (84% and 64%, respectively) for initial management, while surveillance was selected in the high AML probability group (63%). During the 56-month follow-up, 36 (82%) of 44 patients initially surveyed, including 13 of 18 (72%), 6 of 7 (86%), and 17 of 19 (89%) in the low/intermediate/high AML probability groups, respectively, continued surveillance without any progression. CONCLUSIONS: This study confirmed the high diagnostic accuracy for differentiating fp-AMLs. These findings may help in the management of patients with SRMs.

Efficacy and safety of naldemedine for opioid-induced constipation in older patients with cancer: a retrospective study.

BACKGROUND: Opioids are pain relievers that are often associated with opioid-induced constipation (OIC) that worsens with age. We performed a multicenter, retrospective analysis on the efficacy and safety of naldemedine, an opioid receptor antagonist, in treating OIC in patients with cancer (age >75 years). METHODS: The electronic medical records of cancer patients who received naldemedine at 10 Japanese institutions between 7 June 2017 and August 31, 2019, were retrieved. Patients aged ≥75 years who were treated with naldemedine for the first time and hospitalized for at least 7 days before and after initiating naldemedine therapy were included in this analysis. RESULTS: Sixty patients were observed for at least 7 days before and after starting naldemedine. The response rate was 68.3%, and the frequency of bowel movements increased significantly after naldemedine administration in the overall population ( P  < 0.0001) and among those who defecated <3 times/week before naldemedine administration ( P  < 0.0001). Diarrhea was the most frequent adverse event in all grades, observed in 45% of patients, of which 92.6% were Grade 1 or 2. Grade 4 or higher adverse events, including death, were not observed. CONCLUSION: Naldemedine exhibits significant efficacy and safety in OIC treatment in older patients with cancer.

Utility of positive core number on MRI-ultrasound fusion targeted biopsy in combination with PI-RADS scores for predicting unexpected extracapsular extension of clinically localized prostate cancer.

OBJECTIVES: To evaluate the utility of magnetic resonance imaging (MRI) and MRI-ultrasound fusion targeted biopsy (TB) for predicting unexpected extracapsular extension (ECE) in clinically localized prostate cancer (CLPC). METHODS: This study enrolled 89 prostate cancer patients with one or more lesions showing a Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 but without morphological abnormality in the prostatic capsule on pre-biopsy MRI. All patients underwent TB and systematic biopsy followed by radical prostatectomy (RP). Each lesion was examined by 3-core TB, taking cores from each third of the lesion. The preoperative variables predictive of ECE were explored by referring to RP specimens in the lesion-based analysis. RESULTS: Overall, 186 lesions, including 81 (43.5%), 73 (39.2%), and 32 (17.2%) with PI-RADS 3, 4, and 5, respectively, were analyzed. One hundred and twenty-two lesions (65.6%) were diagnosed as cancer on TB, and ECE was identified in 33 (17.7%) on the RP specimens. The positive TB core number was ≤2 in 129 lesions (69.4%) and three in 57 lesions (30.6%). On the multivariate analysis, PI-RADS ≥4 (p = 0.049, odds ratio [OR] = 2.39) and three positive cores on TB (p = 0.005, OR = 3.07) were independent predictors of ECE. Lesions with PI-RADS ≥4 and a positive TB core number of 3 had a significantly higher rate of ECE than those with PI-RADS 3 and a positive TB core number ≤2 (37.5% vs. 7.8%, p < 0.001). CONCLUSIONS: Positive TB core number in combination with PI-RADS scores is helpful to predict unexpected ECE in CLPC.

Unraveling the BMI paradox in different renal cortical tumors: insights from the INMARC registry.

OBJECTIVE: To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). METHODS: We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. RESULTS: A total of 3,880 patients with a median follow-up of 31 (IQR 9-64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I-III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). CONCLUSION: Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes.

Prognostic outcomes in patients with metastatic renal cell carcinoma receiving second-line treatment with tyrosine kinase inhibitor following first-line immune-oncology combination therapy.

OBJECTIVES: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy. METHODS: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO-TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. RESULTS: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non-CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. CONCLUSIONS: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies.

Neoadjuvant Chemoradiotherapy Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer: Analysis of Efficacy and Safety in 119 Patients.

INTRODUCTION: Cisplatin-based systemic chemotherapy is recommended as neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) before radical cystectomy (RC). However, clinical challenges include the possibility of primary chemoresistance and limited feasibility in patients with renal impairment. This study investigated the efficacy and safety profiles of neoadjuvant chemoradiotherapy (NCRT) followed by RC. MATERIALS AND METHODS: We retrospectively analyzed 119 patients with nonmetastatic MIBC, who were pathologically diagnosed with urothelial carcinoma and underwent NCRT before RC. The pathological response to NCRT was evaluated using RC specimens. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were compared according to pathological responses to NCRT. RESULTS: Of the 119 patients, 111 (93%) underwent RC; ypT0 and downstaging to ≤ypT1 were observed in 42 (38%) and 76 (68%) patients, respectively. In the multivariable analysis, smaller tumor size was independently associated with ypT0. During a median follow-up of 5.2 years, 28 (25%) patients developed recurrence and 22 (20%) died of bladder cancer after RC. The 5-year RFS and CSS rates were 75% and 80%, respectively. The 5-year RFS rates in patients with ypT0, ypTa/is/1, and ≥ypT2 were 87%, 87%, and 46%, respectively. Similarly, patients with ypT0 and ypTa/is/1 had more favorable CSS (90% and 87% at 5 years, respectively) than those with ≥ypT2 (60%, P = .001). None of the patients experienced ≥grade 4 adverse events related to NCRT or ≥grade 4 complications of RC. CONCLUSIONS: This study demonstrated sufficient efficacy and safety profile of NCRT followed by RC. Chemoradiotherapy may be a helpful alternative for neoadjuvant treatment before RC.

Incidence and predictors of intraoperative hypotension during transurethral bladder tumor resection with oral 5-aminolevulinic acid.

OBJECTIVES: To analyze the incidence and risk factors of intraoperative hypotension related to photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) with oral 5-aminolevulinic acid (5-ALA). METHODS: We retrospectively analyzed 487 patients with bladder tumors who underwent PDD-TURBT (n = 184) or conventional TURBT (conv-TURBT) (n = 303) between 2018 and 2021. Intraoperative hypotension was defined as hypotension requiring vasopressors during TURBT, and its incidence was compared between the two groups. Potential risk factors of intraoperative hypotension, including preoperative change in mean arterial pressure (MAP), were further investigated in patients receiving PDD-TURBT. RESULTS: The median age was 72 years, 392 patients (81%) were male, and 203 (42%) had hypertension. TURBT was performed under general and spinal anesthesia in 76 (16%) and 411 (84%) patients, respectively. The incidence of intraoperative hypotension was significantly higher in PDD-TURBT compared to conv-TURBT (43% vs. 17%, respectively). The median change in MAP until the induction of anesthesia was +6.5 mmHg (range: -29.0 to +46.3) in the PDD-TURBT group and +14.7 mmHg (range: -35.3 to +67.7) in the conv-TURBT group, showing a significantly smaller increase in the PDD-TURBT group (p < 0.001). In the multivariable analysis for PDD-TURBT patients, advanced age, general anesthesia, and lower MAP change (<+6.5 mmHg) until anesthesia induction were significantly associated with intraoperative hypotension (p = 0.0104, <0.001, and <0.001, respectively). CONCLUSIONS: Intraoperative hypotension occurred more frequently in patients who underwent PDD-TURBT than in those who underwent conv-TURBT. Using oral 5-ALA decreases preoperative blood pressure elevation and may be responsible for intraoperative hypotension.

Longitudinal deterioration in lower urinary tract symptoms after artificial urinary sphincter implantation in patients with a history of pelvic radiation therapy.

OBJECTIVES: To evaluate longitudinal changes in lower urinary tract symptoms (LUTS) after artificial urinary sphincter (AUS) implantation in patients undergoing radiation therapy (RT) in comparison to those in non-irradiated patients. METHODS: This retrospective study included 20 and 51 patients with and without a history of pelvic RT (RT and non-RT group, respectively) who were treated with primary AUS implantation for post-radical prostatectomy incontinence between 2010 and 2020. Longitudinal changes in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the International Prostate Symptom Score (IPSS), and the Overactive Bladder Symptom Score (OABSS) were calculated with a linear mixed model. RESULTS: In the RT and non-RT group, 18 (90%) and 48 (94%) patients achieved social continence, defined as daily pad use ≤1 at 1 month after activation of AUS, respectively (p = .555). During the mean follow-up of 38 months, ICIQ-SF, IPSS, and OABSS significantly improved after AUS implantation in both the RT and non-RT groups. In the RT group, ICIQ-SF, IPSS, and OABSS subsequently deteriorated with a slope of 0.62/year (p = .010), 0.55/year (p = .025), and 0.30/year (p = .007), respectively. In the non-RT group, no significant longitudinal changes in subsequent IPSS and OABSS were observed, although ICIQ-SF significantly deteriorated (0.43/year, p = .006). Comparing between the groups, the slopes of IPSS and OABSS were significantly greater in the RT group than in the non-RT group (p < .001, and .015, respectively). CONCLUSIONS: Longitudinal deterioration in LUTS that improved immediately after AUS implantation was observed in patients with a history of pelvic RT, but not in patients without a history of pelvic RT.

Incidence, risk factors, and significance of 20% decrease from new baseline estimated glomerular filtration rate after radical and partial nephrectomy within 2 years.

OBJECTIVES: To evaluate the incidence and risk factors of a 20% decrease from new baseline (NB)-estimated glomerular filtration rate (eGFR) within 2 years after radical nephrectomy (RN) and partial nephrectomy (PN) and to examine the difference in the incidence of end-stage renal disease (ESRD) with or without the 20% decrease. METHODS: This retrospective study included 238 patients undergoing RN and 369 undergoing PN for cT1a-cT3a renal cancer. The incidence of a 20% decrease from NB-eGFR within 2 years after RN/PN was examined and its potential risk factors including surgery type were assessed by multivariate logistic regression analysis. The development of ESRD was analyzed as an endpoint and its incidence was compared according to the presence or absence of the 20% decrease from NB-eGFR within 2 years. RESULTS: Overall, the 20% decrease from NB-eGFR within 2 years was observed in 37 patients (6.1%), including 10 (4.2%) and 27 (7.3%) after RN and PN, respectively (p = 0.117). Diabetes mellitus, proteinuria, and perioperative complications were shown to be independent risk factors for the 20% decrease from NB-eGFR, while surgery type was not. During the median follow-up of 65 months, the ESRD-free survival rate at 6 years was 75.5% and 99.6% in patients with and without the 20% decrease from NB-eGFR, respectively (p < 0.001), while no significant difference was observed between patients undergoing RN and PN (98.1% and 98.7%, p = 0.561). CONCLUSIONS: Because the incidence of ESRD after the 20% decrease from NB-eGFR within 2 years was as high as 24.5% at 6 years, these patients should be followed with utmost care.

Efficacy and safety of second-line cabozantinib after immuno-oncology combination therapy for advanced renal cell carcinoma: Japanese multicenter retrospective study.

Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice.

Preservation of Erectile and Ejaculatory Functions After Tetramodal Bladder-Sparing Therapy Incorporating Consolidative Partial Cystectomy Against Muscle Invasive Bladder Cancer.

OBJECTIVE: To cross-sectionally assess erectile and ejaculatory functions after tetramodal bladder-sparing therapy consisting of transurethral resection, chemoradiotherapy, and consolidative partial cystectomy in patients with muscle invasive bladder cancer. MATERIALS AND METHODS: Among 72 enrolled male patients who underwent tetramodal bladder-sparing therapy from 2006 to 2019, 42 who visited the outpatient clinic from February to October 2020 received questionnaires. Erectile function, ejaculatory function, and quality of life were assessed using the International Index of Erectile Function short form, the Male Sexual Health Questionnaire Ejaculatory Dysfunction short form, and the Functional Assessment of Cancer Therapy. RESULTS: Among the 42 patients, 9 were excluded because of incomplete responses and 33 were eligible for analyses. The median (range) age at survey and the time from treatment completion to responding to the questionnaires was 70 (50-87) years and 4.2 (0.4-14.0) years, respectively. The median International Index of Erectile Function short form-5 score was 11 (5-25), and 3 (9.1%) and 9 (27.3%) patients had no and mild erectile dysfunction, respectively. The Male Sexual Health Questionnaire Ejaculatory Dysfunction short form results showed that 23 (69.7%) patients responded that they could ejaculate. Patients with higher Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores had better erectile function and quality of life than those with lower Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores. CONCLUSION: Preservation of erectile and ejaculatory functions was demonstrated in muscle invasive bladder cancer patients treated with tetramodal bladder-sparing therapy. In addition to lower urinary tract function, preservation of male sexual function, especially ejaculatory function, in bladder-sparing therapy can be an advantage over radical cystectomy.

Deep-learning prostate cancer detection and segmentation on biparametric versus multiparametric magnetic resonance imaging: Added value of dynamic contrast-enhanced imaging.

OBJECTIVES: To develop diagnostic algorithms of multisequence prostate magnetic resonance imaging for cancer detection and segmentation using deep learning and explore values of dynamic contrast-enhanced imaging in multiparametric imaging, compared with biparametric imaging. METHODS: We collected 3227 multiparametric imaging sets from 332 patients, including 218 cancer patients (291 biopsy-proven foci) and 114 noncancer patients. Diagnostic algorithms of T2-weighted, T2-weighted plus dynamic contrast-enhanced, biparametric, and multiparametric imaging were built using 2578 sets, and their performance for clinically significant cancer was evaluated using 649 sets. RESULTS: Biparametric and multiparametric imaging had following region-based performance: sensitivity of 71.9% and 74.8% (p = 0.394) and positive predictive value of 61.3% and 74.8% (p = 0.013), respectively. In side-specific analyses of cancer images, the specificity was 72.6% and 89.5% (p < 0.001) and the negative predictive value was 78.9% and 83.5% (p = 0.364), respectively. False-negative cancer on multiparametric imaging was smaller (p = 0.002) and more dominant with grade group ≤2 (p = 0.028) than true positive foci. In the peripheral zone, false-positive regions on biparametric imaging turned out to be true negative on multiparametric imaging more frequently compared with the transition zone (78.3% vs. 47.2%, p = 0.018). In contrast, T2-weighted plus dynamic contrast-enhanced imaging had lower specificity than T2-weighted imaging (41.1% vs. 51.6%, p = 0.042). CONCLUSIONS: When using deep learning, multiparametric imaging provides superior performance to biparametric imaging in the specificity and positive predictive value, especially in the peripheral zone. Dynamic contrast-enhanced imaging helps reduce overdiagnosis in multiparametric imaging.

A case of repeat oligoprogressive castration-resistant prostate cancer treated with pulmonary metastasectomy.

Introduction: Several retrospective studies have demonstrated the efficacy of progressive site-directed therapy for oligoprogressive castration-resistant prostate cancer. However, eligible patients for progressive site-directed therapy in these studies were limited to oligoprogressive castration-resistant prostate cancer with bone or lymph node metastases without visceral metastases, and little is known about the efficacy of progressive site-directed therapy for oligoprogressive castration-resistant prostate cancer with visceral metastases. Case presentation: We report a case with castration-resistant prostate cancer previously treated with enzalutamide and docetaxel, in which only a solitary lung metastasis was identified throughout the course of treatment. The patient underwent thoracoscopic pulmonary metastasectomy with a diagnosis of repeat oligoprogressive castration-resistant prostate cancer. Only androgen deprivation therapy was continued and his prostate-specific antigen levels remained undetectable for 9 months after surgery. Conclusion: Our case suggests that progressive site-directed therapy may be effective for carefully selected repeat OP-CRPC with a lung metastasis.

Surgical outcomes of robot-assisted radical cystectomy in octogenarian or older patients: A Japanese nationwide study.

OBJECTIVE: To evaluate the surgical outcomes of robot-assisted radical cystectomy (RARC) in octogenarian or older patients based on a Japanese nationwide database. METHODS: The diagnosis procedure combination database was used to extract the data on radical cystectomy cases. Surgical outcomes of RARC in octogenarian or older patients (older group) were initially compared to those of patients younger than 80 years (younger group). Then, the surgical outcomes of RARC in the older group were compared to those of open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) in the same age group. RESULTS: Between 2018 and 2021, 478 RARC cases in the older group and 2257 RARC cases in the younger group were identified. In the older group, ileal conduit, neobladder, and other urinary diversions were carried out in 352 (73.6%), 22 (4.6%), and 104 (21.8%) patients, respectively. In the older group, when compared with the younger group, the complication rate (24.9%), blood transfusion rate (41.4%), and in-hospital mortality (1.4%) were equivalent, while significantly shorter anesthesia time and longer length of stay were observed in the older group (521.0 ± 140.4 min vs. 595.1 ± 141.71 min, p < 0.01, and 32.9 ± 16.8 days vs. 30.6 ± 17.8 days, p = 0.01, respectively). In the comparison of the surgical outcomes of older patients receiving RARC to those receiving ORC (n = 746) and LRC (n = 375), the RARC group had the lowest complication rate and the shortest length of stay, while the shortest anesthesia time was noted in the ORC group. CONCLUSION: The feasibility of RARC for octogenarian or older patients was demonstrated by the nationwide database study.

Comprehensive investigation of clinicopathological and immunological features to determine prognostic impact in metastatic renal cell carcinoma: The JEWEL study.

OBJECTIVES: Current prognostic models for metastatic renal cell carcinoma (mRCC) are likely inaccurate due to recent treatment advances and improved survival outcomes. The JEWEL study used a data set from patients who received tyrosine kinase inhibitors (TKIs) to explore the prognostic impact of the tumor immune environment in the absence of immune checkpoint inhibitor intervention. METHODS: The primary analysis population comprised 569 of the 770 Japanese patients enrolled in the ARCHERY study who received first-line TKIs. Multivariable Cox proportional hazard models were used to identify factors associated with the primary (overall survival [OS]) and secondary outcomes (treatment duration) using 34 candidate explanatory variables. RESULTS: Median OS was 34.1 months (95% CI, 30.4-37.6) in the primary analysis population. A considerable negative prognostic impact (descriptive p ≤ 0.0005) on OS was seen with lactate dehydrogenase (LDH) >1.5 × upper limit of normal (adjusted HR [aHR], 3.30; 95% CI, 2.19-4.98), Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (aHR, 2.14; 95% CI, 1.56-2.94), World Health Organization (WHO)/International Society of Urological Pathology (ISUP) Grade 4 (aHR, 1.89; 95% CI, 1.43-2.51), C-reactive protein (CRP) level ≥0.3 (aHR, 1.78; 95% CI, 1.40-2.26), and age ≥75 years (aHR, 1.65; 95% CI, 1.24-2.18) in the multivariable analysis. PD-L1 and immunophenotype affected OS in univariable analyses but were not selected in the multivariable model as explanatory variables. CONCLUSIONS: JEWEL identified sex, age, ECOG PS, liver and bone metastases, CRP levels, WHO/ISUP grade, LDH, and albumin levels as key prognostic factors for OS after first-line TKI therapy for mRCC.

Prognostic impact of the radiological infiltrative feature of primary renal tumor in metastatic renal cell carcinoma.

OBJECTIVES: Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic RCC Database Consortium (IMDC) risk model. METHODS: We retrospectively analyzed 91 patients with previously untreated mRCC. Dynamic computed tomography of the primary renal tumor was reviewed to assess r-IF, defined as a focally/extensively ill-defined tumor interface with normal renal parenchyma. RESULTS: The median age was 67 years, and 69 patients (76%) were men. Prior nephrectomy was performed in 47 patients (52%). The median size of the primary renal tumor was 6.7 cm, and 50 patients (55%) presented with cT3-4 stage. Overall, 25 (28%)/52 (57%)/14 (15%) patients were classified into IMDC favorable/intermediate/poor-risk groups, respectively. An image review identified r-IFs in the primary renal tumor in 40 patients (44%). The incidences of r-IFs were 28%/46%/64% in IMDC favorable/intermediate/poor-risk groups, respectively. During a median follow-up of 2.6 years, 31 patients (34%) died of RCC. On multivariable analysis, r-IF and IMDC intermediate-poor risks were independently associated with poor cancer-specific survival (CSS). Two-year CSS were 64%/87% in patients with/without r-IF, respectively. C-index was improved from 0.73 to 0.81 by adding r-IF to the IMDC risk factors. CONCLUSIONS: R-IF of the primary renal tumor was an independent risk factor for poor CSS in patients with mRCC, which may improve the prognostic accuracy when combined with the IMDC risk model.

Efficacy and safety of naldemedine treatment for opioid-induced constipation in gastrointestinal cancer: a retrospective analysis.

BACKGROUND: Gastrointestinal cancers are one of the most common cancer cases worldwide. Cancer treatment is multidisciplinary, which includes opioid pain management. Opioid analgesics cause opioid-induced constipation (OIC) with the onset of effect. Naldemedine, a peripheral opioid receptor antagonist, is an OIC-modifying agent, but no focused efficacy and safety analysis has been conducted for its use in gastrointestinal cancers. METHODS: We retrospectively evaluated patients with gastrointestinal cancer treated with naldemedine at ten institutions in Japan from June 2017 to August 2019. Patients with gastrointestinal cancer who initiated treatment with opioids during hospitalization and were treated with naldemedine for the first time were included in the study. The gastrointestinal cancer types included were esophageal, gastric, small bowel, and colorectal cancers. We assessed the defecation frequency before and after the initiation of naldemedine use. Responders were defined as patients who defecated three or more times/week, with an increase from the baseline of one or more bowel movements/week over seven days after starting naldemedine. RESULTS: Thirty-three patients were observed for one week before and after starting naldemedine. Twenty-one patients had an increase in defecation frequency of at least three times per week or at least once per week above the baseline. The response rate was 63.6% [95% confidence interval (CI): 46.6-77.9%]. The median number of bowel movements for a week before and after the initiation of naldemedine treatment was 3 (range, 0-13) and 7 (range, 1-39), respectively, in the overall population (n=33), with a significant increase in defecation frequency following naldemedine administration (Wilcoxon signed rank test, P<0.005). Diarrhea was the predominant gastrointestinal symptom, with 13 (39.4%) patients experiencing grade 1 and none experiencing grade 3 or grade 4 adverse events. The frequency of other grade 1 adverse events was low abdominal pain in two patients, nausea in two patients, and anorexia in one patient, without any grade 2-4 adverse events. CONCLUSIONS: The results of the study suggest that naldemedine is effective and safe in clinical practice for gastrointestinal cancer treatment.