Outcomes and prognostic factors in patients with synchronous and metachronous oligometastatic urothelial carcinoma with visceral metastases.

OBJECTIVES: To evaluate the clinical characteristics of oligometastatic disease (OMD) in metastatic urothelial carcinoma (mUC) with visceral metastases when classified into synchronous and metachronous metastases. METHODS: Of 957 cases of de novo mUC treated between 2008 and 2023, 374 with visceral metastases were analyzed. Cases were classified into OMD with up to three metastatic lesions and polymetastatic disease (PMD), and into synchronous and metachronous metastases. The clinical characteristics and overall survival (OS) for each group were analyzed. RESULTS: Overall, 196 (52.4%) had synchronous metastasis and 178 (47.6%) had metachronous metastasis. Median OS for synchronous metastases was significantly shorter than for metachronous metastases (12.1 months vs. 15.3 months, p = 0.011). Among the synchronous metastases, 48 (24.5%) were OMD and 148 (75.6%) were PMD. There was no significant difference in OS between the OMDs and PMDs (median 14.9 months vs. 11.7 months, p = 0.32), and only decreased albumin level was identified as a significant predictor of poor OS. Among the metachronous metastases, 64 (36.0%) were OMD and 114 (64.0%) were PMD. There was no significant difference in OS between the OMD and PMD (median 21.2 months vs. 15.0 months, p = 0.35), and no significant predictors of poor OS were identified. CONCLUSIONS: For mUC with visceral metastases, the timing of metastasis appearance was associated with prognosis, with synchronous metastases being a poorer prognostic factor compared to metachronous metastases. There was no prognostic difference between OMD and PMD with visceral metastases when classified into synchronous or metachronous metastases.

Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001). CONCLUSION: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Surgical outcomes and predictive value for major complications of robot-assisted radical cystectomy of real-world data in a single institution in Japan.

OBJECTIVE: The objective of the study was to describe the surgical outcome of robot-assisted radical cystectomy and predictive factors for major complications in real-world clinical practice at a single institution in Japan. METHODS: We retrospectively analyzed 208 consecutive patients undergoing robot-assisted radical cystectomy at our institution between 2019 and 2023. Patient and disease characteristics, intraoperative details, and perioperative outcomes were reviewed. Postoperative complications were defined as minor complications (Clavien-Dindo grades 1-2) or major complications (grades 3-5). Predictors of complications were examined using multivariable logistic analysis. RESULTS: Overall, 147 men and 61 women, median age 70 years (interquartile range, 62-77), were included in this study. Median operative time and estimated blood loss were 8.4 h and 185 mL, respectively; 11 patients (5%) received intraoperative blood transfusions. For urinary diversions, ileal conduit, neobladder, and cutaneous ureterostomy were performed in 153 (74%), 49 (24%), and 6 (3%) patients, respectively. Urinary diversions were primarily performed with extracorporeal urinary diversion. In total, 140 complications occurred in 111 patients (53%) within 30 days. Of these patients, 31 major complications occurred in 28 patients, and one perioperative death (0.5%) with a postoperative cardiovascular event. Multivariable analysis showed only prolonged operative time (odds ratio: 4.34, 95% confidence interval: 1.82-10.35, p < 0.01) was the independent risk factor for major complications. CONCLUSIONS: This study reports surgical outcomes at our single institution. Prolonged operative time was a significant prognostic factor for major complications. As far as we know, this study reports the largest number of robot-assisted radical cystectomy cases at a single center in Japan.

A case of neoadjuvant chemotherapy-resistant muscle-invasive bladder cancer that markedly responded to pembrolizumab before conversion radical cystectomy.

Introduction: Recently, perioperative use of immune checkpoint inhibitors has improved the prognosis of muscle-invasive bladder cancer. It is unclear whether radical cystectomy or systemic pembrolizumab is the optimal next treatment in patients with muscle-invasive bladder cancer and progressive disease in the pelvic lymph node following neoadjuvant chemotherapy (NAC). Case presentation: A 62-year-old woman with cT3N0M0 bladder cancer and high programmed death-ligand 1 expression developed solitary obturator lymph node metastasis following 5 cycles of neoadjuvant chemotherapy. Six subsequent cycles of pembrolizumab shrank the lymph node significantly, and conversion radical cystectomy was planned. Pathologically, only carcinoma in situ around the scar of transurethral resection of bladder tumor remained in the primary tumor, and the accumulation of foamy macrophages and fibrosis without viable tumor cells was observed in the dissected lymph node. Eighteen months passed without a recurrence following radical cystectomy. Conclusion: Pembrolizumab administration before radical cystectomy achieved a good response in a patient with obturator lymph node metastasis following neoadjuvant chemotherapy.

Prognostic Significance of Immune-related Adverse Events in Metastatic Renal Cell Carcinoma Patients Treated With Immune-checkpoint-inhibitors.

BACKGROUND/AIM: Immune-related adverse events (irAEs) develop in a subset of patients with metastatic renal cell carcinoma (mRCC) treated with immune-checkpoint-inhibitors (ICIs). Evidence regarding the prognostic impact of irAEs remains limited in these patients. PATIENTS AND METHODS: Ninety-one consecutive patients with mRCC treated with ICIs were retrospectively analyzed. Overall survival (OS) rates were estimated using the Kaplan-Meier method. In multivariate analysis, predictors of OS were analyzed using the Cox-proportional-hazards-model. RESULTS: Twenty-nine patients were treated with the combination of nivolumab plus ipilimumab. According to International Metastatic RCC Database Consortium risk classification, 27/47/17 patients were classified into favorable/intermediate/poor risk categories. The 1, 3, and 5-year OS-rates were 89, 70, and 57%, respectively. A total of 67 irAEs occurred in 44 patients (48%), including 15 patients with grade 3-4. OS was significantly longer in patients with irAEs (p=0.01). In multivariate analysis, Karnofsky performance status, prior nephrectomy, and irAEs were independent significant predictors of OS. CONCLUSION: In our study, irAEs were significantly associated with OS in mRCC patients treated with ICIs.

A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL).

BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.

Geriatric Nutritional Risk Index as a Predictor of Prognosis in Metastatic Renal Cell Carcinoma Treated with Nivolumab.

BACKGROUND: The Geriatric Nutritional Risk Index (GNRI) has been reported as a screening tool to assess the nutrition-related risk with mortality in older patients and those with the various diseases. However, the prognostic value of GNRI in metastatic renal cell carcinoma (mRCC) patients receiving nivolumab therapy remains unclear. METHODS: Fifty-six consecutive patients with mRCC receiving nivolumab between September 2013 and August 2020 at our institution were retrospectively analyzed. The survival outcomes and prognostic factors associated with overall survival (OS) were statistically analyzed. RESULTS: Thirteen and forty-three patients were classified with low (GNRI < 92) and high (GNRI ≥ 92) GNRI, respectively. Patients with low GNRI demonstrated significantly shorter OS (P = 0.0002) than those with high GNRI. In multivariate analysis, GNRI at the time of nivolumab (P = 0.008) was extracted as the predictor for OS in addition to Karnofsky performance status (KPS) (P = 0.016). Integration of the GNRI into the International Metastatic Renal Cell Cancer Database Consortium (IMDC) risk classification improved the c-index from 0.761 to 0.833 (combination of GNRI with IMDC risk classification) and to 0.778 (substitution of GNRI with KPS in IMDC risk classification). CONCLUSIONS: GNRI was a significant prognostic biomarker in mRCC patients receiving nivolumab.

Renal function outcome after selective bladder-preserving tetramodality therapy consisting of maximal transurethral resection, induction chemoradiotherapy and consolidative partial cystectomy in comparison with radical cystectomy for patients with muscle-invasive bladder cancer: a two-centre retrospective study.

OBJECTIVE: To compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC). METHODS: This study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed. RESULTS: The number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of -0.7 and -1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC. CONCLUSIONS: RF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.

Tumor shrinkage patterns of nivolumab monotherapy in metastatic renal cell carcinoma.

OBJECTIVES: To investigate the tumor shrinkage patterns of patients with metastatic renal cell carcinoma treated with nivolumab monotherapy. METHODS: Forty-four consecutive patients with metastatic renal cell carcinoma treated with nivolumab monotherapy (81 metastatic and four primary lesions) between September 2013 and December 2020 were retrospectively analyzed. The tumor shrinkage rate of individual visceral and lymph node metastatic lesions and the primary site lesions treated with nivolumab monotherapy, as well as the association between overall survival and pretreatment tumor size, were statistically assessed. RESULTS: Pretreatment tumor size for the total and individual target lesions, which included kidneys, lungs, pancreas, and lymph nodes, were not correlated with tumor shrinkage rate. The tumor shrinkage rate was found to have no significant association with pretreatment tumor size between any organ. In addition, there is no significant difference in tumor shrinkage rate between larger (>median value) and smaller (

Improvement of Medical Treatment in Japanese Patients With Metastatic Renal Cell Carcinoma.

Background/Aim: To evaluate the relationship between treatment period and overall survival (OS) and to identify clinical factors associated with OS in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Two hundred thirteen consecutive patients with mRCC receiving systemic therapy between 2008 and 2020 were divided into two groups: those starting first-line therapy in 2008-2015 (n=133) and those in 2016-2020 (n=80). Clinical factors associated with OS were retrospectively and statistically analyzed. Results: Median OS and one-, three- and five-year OS rates were not reached and 88.7%, 64.9%, and 64.9% in patients treated in 2016-2020; 31.4 months and 78.5%, 42.8% and 34.2% in 2008-2015 (p=0.0013). Multivariate analysis identified the period in which first-line therapy was started as the strongest predictor for OS (p=0.0002). Conclusion: OS was significantly better in mRCC patients treated in 2016-2020 than in 2008-2015. Treatment period was the strongest predictor for OS.

Early Serum and Hematological Responses to Pembrolizumab Therapy as Predictors of Survival in Metastatic Urothelial Cancer.

BACKGROUND: In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses. PATIENTS AND METHODS: Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival. RESULTS: The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR>3, LDH>upper limit of normal (ULN), and CRP>0.5 mg/dl after 3 weeks of pembrolizumab treatment (p<0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p<0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell's C-indices for NLR >3, LDH >ULN, CRP >0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37). CONCLUSION: Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.

Clinical Outcome and Prognostic Variables of Second-line Therapy for Patients With Castration-resistant Prostate Cancer After Failure of First-line Androgen Receptor Axis-targeted Therapy.

BACKGROUND: Despite the rapid introduction of androgen receptor-targeted agents (ARTA) into clinical practice for castration-resistant prostate cancer (CRPC), the optimal treatment strategy after first-line ARTA remains unclear. The object of this study was to clarify clinical outcomes of second-line therapy for CRPC after first-line ARTA. PATIENTS AND METHODS: The medical records of 130 consecutive patients with CRPC with disease progression during first-line ARTA and who started second-line therapy at our Institution between 2014 and 2020 were analyzed. RESULTS: A total of 130 patients with CRPC were identified. Ninety patients underwent ARTA-ARTA treatment, and 40 patients underwent ARTA-docetaxel treatment. The median observation period after second-line ARTA or docetaxel administration was 14.2 months. The prostate-specific antigen response rates overall, and after second-line ARTA, and docetaxel were 26.8%, 24.7%, and 31.6%, respectively. The median progression-free survival (PFS) and 1- and 2-year PFS rates of second-line therapy were 7.9 months and 34.6% and 15.4%, respectively. The median overall survival (OS) and 1- and 2-year OS rates were 27.4 months and 81.8%, and 54.9%, respectively. Multivariate analyses for OS disclosed that a C-reactive protein over the upper limit of normal and time from first-line ARTA to progression under 12 months were associated with shorter OS. Prostate-specific antigen response, PFS and OS of second-line therapy were not significantly different between second-line ARTA and docetaxel. CONCLUSION: There was no significant difference in OS between ARTA-ARTA and ARTA-docetaxel groups in the present study, suggesting that second-line ARTA might be the preferred treatment after initial failure of ARTA.

Robotic-assisted laparoscopic surgery for synchronous primary rectal and prostate cancer: Initial case series.

Few studies have reported the simultaneous resection of synchronous rectal and prostate cancers. Here, we report five patients undergoing simultaneous robotic-assisted laparoscopic surgery (RALS) for synchronous rectal and prostate cancer. Rectal cancer operative procedures were high anterior (n =1), intersphincteric (n =2), or abdominoperineal (n =2) resection, followed by radical prostatectomy with vesico-urethral anastomosis. There were no conversions to open surgery, with R0 resection achieved for all rectal cancer cases. The median operative time was 629 (range, 431-764) minutes, and the median estimated blood loss was 100 (range, 20-345) mL. There was one case of colorectal anastomotic leakage requiring covering ileostomy, and two cases of vesico-urethral anastomotic leakage requiring Foley catheter reinsertion. Ileostomies were finally closed in all patients. Pad-free or safety-pad usage for post-surgical urinary incontinence at 6 and 12 months was 3/5 and 5/5, respectively. Simultaneous RALS for synchronous rectal and prostate cancer may offer a safe and feasible approach in selected patients.

Predictive ability of prebiopsy magnetic resonance imaging and biopsy for side-specific negative lymph node metastasis at radical prostatectomy.

BACKGROUND: Prostate cancer localization is reportedly associated with the laterality of lymph node metastasis. Thus, it may be feasible to predict side-specific lymph node metastasis (LNM) at radical prostatectomy (RP). To investigate whether multiparametric magnetic resonance imaging and biopsy findings can predict side-specific negative LNM and to explore the feasibility of unilateral lymph node dissection (LND) at RP. METHODS: A total of 500 patients who were diagnosed with prostate cancer with prebiopsy multiparametric magnetic resonance imaging of the prostate and subsequent prostate biopsy and who underwent RP and extended LND without neoadjuvant treatment were enrolled. Multiparametric magnetic resonance imaging, biopsy findings, and LNM were assessed for each side. The negative predictive value (NPV) of multiparametric magnetic resonance imaging or biopsy or both for ipsilateral LNM was examined. RESULTS: LNM was found in 9.2% (46/500) and 15.6% (28/180) of patients in the overall and high-risk cohorts, respectively. Magnetic resonance imaging and biopsy findings were negative in 408 and 262 sides, respectively, in the overall cohort and 144 and 100 sides, respectively, in the high-risk cohort. The NPVs of magnetic resonance imaging, biopsy, and both for ipsilateral LNM were 98.3%, 98.5%, and 99.1%, respectively, in the overall cohort, and 95.8%, 97.1%, and 97.6%, respectively, in the high-risk cohort. CONCLUSIONS: Unilateral LND may be indicated based on side-specific LNM risk as assessed by prebiopsy multiparametric magnetic resonance imaging and biopsy.

Improving Accuracy, Reliability, and Efficiency of the RENAL Nephrometry Score With 3D Reconstructed Virtual Imaging.

OBJECTIVE: To clarify the diagnostic performance of the three-dimensional reconstructed virtual image (3D-RVI) in evaluating RENAL nephrometry score (RENAL-NS). METHODS: This study included 130 patients who underwent preoperative contrast-enhanced computed tomography followed by partial nephrectomy for renal tumors suggestive of renal cell carcinoma. RENAL-NS was calculated prior to the surgery, and tumor resection was performed referring to the score. We retrospectively reviewed preoperative contrast-enhanced computed tomography images. We calculated the inter-observer variability of RENAL-NS using 3D-RVI vs two-dimensional (2D) imaging and compared the ability of RENAL-NS using 3D-RVI vs 2D imaging to predict the risk of opening of the urinary collecting system. We also compared the two modalities for the time required to evaluate RENAL-NS. RESULTS: RENAL-NS evaluated using 3D-RVI showed a higher inter-observer agreement compared to 2D-imaging (rs = 0.85 vs rs = 0.65). The "nearness to sinus" score was more strongly associated with the opening of the urinary collecting system when evaluated using 3D-RVI than 2D-imaging (AUC = 0.71 vs AUC = 0.57, P = .016). RENAL-NS using 2D-imaging required a significantly longer time compared to 3D-RVI (P = .036). CONCLUSION: Using 3D-RVI improves the accuracy, reliability and efficiency of RENAL-NS evaluation in preoperative assessment and can play an important role in preoperative assessment and intraoperative navigation.

The utility of diffusion-weighted whole-body imaging with background body signal suppression in detecting metastatic lesion of germ cell carcinoma.

INTRODUCTION: Although the utility of diffusion-weighted whole-body imaging with background body signal suppression for assessing lymph node involvement or distant metastasis is renowned in many cancers, only few studies have revealed its utility for germ cell carcinoma. Some metastatic lesions of germ cell carcinomas are difficult to detect by conventional imaging. CASE PRESENTATION: We report a case of a 70-year-old man with relapsed retroperitoneal germ cell tumor. Although his human chorionic gonadotropin levels increased, conventional imaging analysis showed no evidence of recurrence. Diffusion-weighted whole-body imaging with background body signal suppression was performed to search the metastatic lesion and detected metastatic sacral lesions. The patient responded well to local radiotherapy added to the steroid pulse and salvage chemotherapy and achieved long-term recurrence-free survival. CONCLUSION: Diffusion-weighted whole-body imaging with background body signal suppression has the potential to detect metastatic lesions not usually detected by conventional imaging methods.

External validation of the Briganti 2019 nomogram to identify candidates for extended pelvic lymph node dissection among patients with high-risk clinically localized prostate cancer.

BACKGROUND: We aimed to establish an external validation of the Briganti 2019 nomogram in a Japanese cohort to preoperatively evaluate the probability of lymph node invasion in patients with high-risk, clinically localized prostate cancer. METHODS: The cohort consisted of 278 patients with prostate cancer diagnosed using magnetic resonance imaging-targeted biopsy who underwent radical prostatectomy and extended pelvic lymph node dissection from 2012 to 2020. Patients were rated using the Briganti 2019 nomogram, which evaluates the probability of lymph node invasion. We used the area under curve of the receiver operating characteristic analysis to quantify the accuracy of the nomogram. RESULTS: Nineteen (6.8%) patients had lymph node invasion. The median number of lymph nodes removed was 18. The area under the curve for the Briganti 2019 was 0.71. When the cutoff was set at 7%, 84 (30.2%) patients with extended pelvic lymph node dissection could be omitted, and only 1 (1.2%) patient with lymph node invasion would be missed. Sensitivity, specificity, and negative predictive values at the 7% cutoff were 94.7, 32.0, and 98.8%, respectively. CONCLUSION: This external validation showed that the Briganti 2019 nomogram was accurate, although there may still be scope for individual adjustments.

Japanese single-institution analysis of mitotane for patients with adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. While mitotane is the only agent approved for ACC, clinical data are scarce, especially in the Asian population. We reviewed 10 patients with ACC who received mitotane as a single agent or in combination with other agents in our institution. Patient characteristics, clinical outcomes, and toxicities were analyzed. Mitotane was administered to 2 patients as an adjuvant therapy and to 8 patients for systemic control. In the latter 8 patients, 1 patient had locally advanced disease and 1 had metastatic disease at the time of initial diagnosis, whereas the other 6 patients experienced metastatic relapse at mitotane initiation. The administered regimen was mitotane alone in 7 patients, and mitotane plus cytotoxic chemotherapy in 3 patients. The initial daily mitotane dose was 3.0 g in 2 patients, 1.5 g in 7 patients, and 1.0 g in 1 patient. The median duration of treatment was 3.7 (range, 0.7-22.1) months. In 8 systemic cases, the median overall survival from chemotherapy initiation was 7.2 months, and only 1 patient survived over 1 year. The median interval from mitotane termination to death in systemic cases was 2.8 months, and the cause was progressive disease in 4 patients and toxicity (hallucination, mycobacteriosis, or liver injury) in 3 patients. As a second-line regimen, 2 systemic cases and 1 adjuvant case were enrolled in clinical trials. Our analysis exhibited extremely poor prognosis under mitotane-based regimens, and further treatment strategies are warranted to improve outcomes.