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1.
Cureus ; 16(4): e58558, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38770464

ABSTRACT

Premature chromatid separation (PCS)/mosaic variegated aneuploidy (MVA) syndrome is a rare chromosome instability syndrome. This syndrome is inherited in an autosomal recessive pattern. Although heterozygous carriers of a monoallelic mutation reportedly have a normal phenotype, PCS-positive cells are found at a higher rate in such carriers than in the general population. We herein report a case in which a PCS carrier was incidentally diagnosed during investigation of male infertility. A diagnosis of nonobstructive azoospermia was made, and chromosome analysis revealed the PCS trait in 81 of 200 cells (40.5%), indicating that the patient was a PCS carrier. PCS carriers are not uncommon, and if both members of a couple are carriers, there would be a 25% likelihood of the child presenting with PCS syndrome. Therefore, a clinical psychological approach that includes genetic counseling should be considered before proceeding to microsurgical testicular sperm extraction.

2.
Medicina (Kaunas) ; 60(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38674197

ABSTRACT

Background and Objectives: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone density and increased bone fractures as side effects of ADT have emerged. The prevalence of osteoporosis in Japanese men was 4.6%. The purpose of this study was to evaluate the effect of osteoporosis treatment in prostate cancer patients who underwent ADT in Japan. Materials and Methods: The subjects were 33 male patients who had undergone ADT for prostate cancer, who were noted to have decreased bone density. Mean age was 76.2 ± 7.7 years (64-87). Medications included vitamin D in one case, bisphosphonates (BP) in 27 cases, and denosumab in five cases. The evaluation method examined the rate of change in bone mineral density (BMD) before osteoporosis treatment and 1 year after. For comparison, a group without osteoporosis treatment intervention (n = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. Results: The percentage changes in BMD before and 1 year after treatment were as follows: lumbar spine, 7.1 ± 5.8% in the treatment group versus -3.9 ± 4.1% in the no treatment group; femoral neck, 5.5 ± 6.2% in the treatment group versus -0.9 ± 3.9% in the no treatment group; total femur, 6.6 ± 6.4% in the treatment group versus the no treatment group which was -1.7 ± 3.2%. In all cases, there was a clear significant difference (p < 0.01). The percent change in TBS was further calculated in the same manner. There was no significant difference between the two groups: +1.7 ± 3.8% in the treated group versus +0.3 ± 4.1% in the untreated group. Conclusions: Osteoporosis treatment in Japanese patients with prostate cancer on ADT therapy was found to significantly increase BMD compared to the untreated group. BP and denosumab were found to be very effective in increasing BMD.


Subject(s)
Androgen Antagonists , Bone Density Conservation Agents , Bone Density , Denosumab , Osteoporosis , Prostatic Neoplasms , Humans , Male , Osteoporosis/drug therapy , Aged , Japan/epidemiology , Androgen Antagonists/adverse effects , Androgen Antagonists/therapeutic use , Prostatic Neoplasms/drug therapy , Bone Density/drug effects , Aged, 80 and over , Middle Aged , Denosumab/therapeutic use , Denosumab/adverse effects , Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Diphosphonates/adverse effects , Vitamin D/therapeutic use
4.
Int Cancer Conf J ; 13(2): 103-107, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38524643

ABSTRACT

Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its therapeutic strategy remains unestablished. Here, we report a case of bladder SCC in which multidisciplinary treatment has resulted in relatively long-term survival. A 68-year-old man presented with gross hematuria. A cystoscopy revealed an invasive bladder tumor. A transurethral resection of bladder tumor (TURBT) was performed, and the pathological diagnosis was SCC. After systemic chemotherapy using etoposide and carboplatin and subsequent TURBT, a radical cystectomy and ileal conduit were performed. Three months postoperatively, the patient had a recurrence in the para-aortic lymph node. Systemic combination chemotherapy with carboplatin plus irinotecan (CBDCA + CPT-11) was administered, followed by amrubicin and an immune checkpoint inhibitor. In addition to this treatment, radiation therapy for the metastatic region led to the reduction of pain and shrinkage of the metastatic lesion. The patient survived for 2 years after the initial diagnosis. Our report indicates that multidisciplinary treatment can be effective for SCC of the bladder, and a therapeutic strategy including the identification of novel biomarkers should be established.

5.
Can Urol Assoc J ; 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38319607

ABSTRACT

INTRODUCTION: We aimed to clarify the therapeutic outcome of combination therapy using immune-checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs) for metastatic non-clear-cell renal cell carcinoma (nccRCC). METHODS: We have been retrospectively investigating the therapeutic efficacy and prognosis in 36 patients with metastatic nccRCC undergoing combination therapy using two ICIs, ipilimumab plus nivolumab (ICI-ICI), and ICI plus TKI (ICI-TKI), at Kobe University and affiliated institutions since 2018. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse event (AE) were compared. RESULTS: The first-line regimens was ICI-ICI regimens in 26 cases and ICI-TKI regimens in 10 cases. The ORRs in the ICI-ICI and ICI-TKI groups were 34.6 and 30.0%, respectively (p=0.9433). The 50% PFS for the ICI-TKI group was 9.7 months, significantly longer than that for the ICI-ICI group (4.6 months, p=0.0499), and there was no significant difference in OS between them (p=0.3984). There was no significant difference in the occurrence rate of AE for below grade 2 (p=0.8535) nor above grade 3 (p=0.3786) between the ICI-ICI and ICITKI groups. CONCLUSIONS: From our analysis of real-world data, a better outcome of PFS was expected in the ICI-TKI group compared with that in the ICI-ICI group, while there was no significant difference in OS or ORR.

6.
Int J Urol ; 31(5): 552-559, 2024 May.
Article in English | MEDLINE | ID: mdl-38303567

ABSTRACT

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.


Subject(s)
Carcinoma, Transitional Cell , Humans , Male , Female , Aged , Japan/epidemiology , Middle Aged , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/mortality , Aged, 80 and over , Immune Checkpoint Inhibitors/therapeutic use , Treatment Outcome , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/mortality , Retrospective Studies , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology , Urologic Neoplasms/mortality , Disease Progression , Practice Patterns, Physicians'/statistics & numerical data
7.
IJU Case Rep ; 7(1): 30-33, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38173447

ABSTRACT

Introduction: Leiomyosarcoma of the inferior vena cava is associated with poor prognosis. Complete resection is the only curative treatment. We present a patient with this disease in whom cine magnetic resonance imaging was valuable in selecting the surgical strategy and mitigating invasiveness. Case presentation: A 68-year-old woman presented with right-sided abdominal pain. Computed tomography revealed an 86 mm tumor in the right retroperitoneal space that extended into the inferior vena cava and reached superiorly to the right atrium. Percutaneous needle biopsy confirmed leiomyosarcoma. Cine magnetic resonance imaging demonstrated no adhesions between the tumor and the upper segment of inferior vena cava wall, nor with the right atrial wall, indicating resectability. Radical tumor resection was successfully performed without requiring thoracotomy. Conclusion: Cine magnetic resonance imaging appears to be useful in inferior vena cava leiomyosarcoma for evaluating adhesions between the tumor and vessel wall.

8.
IJU Case Rep ; 7(1): 60-63, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38173458

ABSTRACT

Introduction: Renal cell carcinoma with an inferior vena cava tumor thrombus is a challenging disease that requires a multimodal treatment approach. Pembrolizumab plus lenvatinib has displayed promising efficacy in metastatic renal cell carcinoma. Case presentation: A 61-year-old man was diagnosed with metastatic renal cell carcinoma and a tumor thrombus adhering to the inferior vena cava wall by cine magnetic resonance imaging. After 6 months of pembrolizumab and lenvatinib therapy, tumor shrinkage was detected, excluding the advanced portion of the inferior vena cava thrombus, and nephrectomy and thrombectomy were performed. Adhesion of the tumor thrombus to the inferior vena cava wall was observed during surgery. Resection produced a remarkable pathological complete response with no viable cells in the resected specimens, including the thrombus site. Conclusion: This case highlights the potential of pembrolizumab plus lenvatinib for treating advanced renal cell carcinoma with an inferior vena cava thrombus and the utility of cine magnetic resonance imaging for evaluating thrombus adhesion to the inferior vena cava.

9.
IJU Case Rep ; 6(6): 357-361, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37928291

ABSTRACT

Introduction: The performance of robot-assisted laparoscopic pyeloplasty has recently been increasing in frequency. However, patients with duplicated renal pelvises and ureters can present challenges. Case presentation: A 71-year-old woman presented with flank pain and was diagnosed with ureteropelvic junction obstruction with an incomplete duplicated collecting system. Preoperative imaging did not reveal the details of the stenosis. Therefore, three reconstructive procedures were prepared: The Anderson-Hynes procedure, end-to-side pyeloureterostomy, and upper pole ureter to lower pole pyeloplasty with the Anderson-Hynes procedure for the lower pole. These procedures were determined by the length of the intact ureter and the presence of crossed vessels. During the surgery, the crossing vein was severed, allowing successful reconstruction with Anderson-Hynes anastomosis. Conclusion: Preoperative evaluation and preparation of multiple surgical techniques are crucial in robot-assisted laparoscopic pyeloplasty for incomplete duplicated collecting systems.

10.
Clin Case Rep ; 11(11): e8128, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37953896

ABSTRACT

Key Clinical Message: Renal cell carcinoma as a secondary malignant neoplasm is relatively rare; however, the possibility of secondary renal cell carcinoma following chemoradiotherapy for childhood nephroblastoma should be considered. Abstract: The occurrence of secondary renal cell carcinoma (RCC) following chemoradiotherapy for nephroblastoma is relatively rare, especially in microphthalmia transcription factor family translocation renal cell carcinoma. A 13-year-old Japanese male was referred to our department for treatment of a right kidney mass. The patient had undergone open left nephrectomy and adjuvant chemotherapy for nephroblastoma, 12 years before. Diagnostic imaging revealed a tumor in the right kidney and a lesion suspected to be metastasis in the left eighth rib. Chromophobe RCC or translocation RCC was suspected from the imaging pattern. TNM classification was cT1aN0M1, and the clinical stage was IV. Partial nephrectomy by robot-assisted surgery for the right renal tumor and resection of the left eighth rib were performed. Pathologically, the renal tumor was diagnosed as translocation RCC, and the rib lesion demonstrated no evidence of malignancy. We are currently undergoing imaging follow-up and the patient has been recurrence-free for 15 months. In this study, we present a rare case of secondary translocation RCC after successful treatment of nephroblastoma.

11.
Oncol Lett ; 26(5): 470, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37809051

ABSTRACT

The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first-line regimens included the ICI-ICI and ICI-TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 10.5 and 8.2 months (P=0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI-TKI group was significantly higher than that in the ICI-ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real-world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI-TKI in patients without upfront CN.

12.
Prostate ; 83(13): 1270-1278, 2023 09.
Article in English | MEDLINE | ID: mdl-37316357

ABSTRACT

BACKGROUND: The objective of this study was to evaluate the background and treatment course of patients with metastatic prostate cancer (PC), with a particular focus on radiographic progression in the absence of prostate-specific antigen (PSA) progression. METHODS: The study population consisted of 229 patients with metastatic hormone-sensitive PC (HSPC), who received prostate biopsy and androgen deprivation therapy at Kobe University Hospital between January 2008 and June 2022. Clinical characteristics were retrospectively evaluated using medical records. PSA progression-free status was defined as ≤1.05 times greater than that from 3 months before. Multivariate analyses were performed using the Cox proportional hazards regression model to identify parameters associated with time to progression on imaging without PSA elevation. RESULTS: A total of 227 patients with metastatic HSPC without neuroendocrine PC were identified. The median follow-up period was 38.0 months, with a median overall survival of 94.9 months. Six patients exhibited disease progression on imaging without PSA elevation during HSPC treatment, three during first-line castration-resistant PC (CRPC) treatment, and two during late-line CRPC treatment. The rate of disease progression without PSA elevation at 3 years after treatment initiation was 7.4%. Multivariate analysis revealed that organ metastases and upfront treatment with docetaxel or androgen receptor axis-targeted therapy were independent prognostic factors for imaging progression without PSA elevation. CONCLUSIONS: Disease progression on imaging without PSA elevation occurred not only during HSPC treatment and first-line CRPC treatment, but also during late-line CRPC treatment. Patients with visceral metastases or those treated with upfront androgen receptor axis-targeted or docetaxel may be more prone to such progression.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Docetaxel/therapeutic use , Prostate-Specific Antigen/therapeutic use , Receptors, Androgen , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Prostatic Neoplasms, Castration-Resistant/drug therapy , Androgen Antagonists/therapeutic use , Retrospective Studies , Disease Progression , Treatment Outcome
13.
Int J Urol ; 30(9): 779-786, 2023 09.
Article in English | MEDLINE | ID: mdl-37317886

ABSTRACT

OBJECTIVES: We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS: This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS: Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS: RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Urologic Neoplasms , Humans , Aged , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/pathology , Urologic Neoplasms/pathology , Retrospective Studies , Prognosis
14.
Sci Rep ; 13(1): 9994, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37340017

ABSTRACT

Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60-70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.


Subject(s)
Cancer Vaccines , Carcinoma, Renal Cell , Kidney Neoplasms , Mouth Neoplasms , Animals , Mice , Carcinoma, Renal Cell/therapy , Bifidobacterium , Nivolumab , Mouth Neoplasms/therapy , Disease Models, Animal , Kidney Neoplasms/therapy , Immunotherapy
16.
Int J Urol ; 30(9): 746-752, 2023 09.
Article in English | MEDLINE | ID: mdl-37130778

ABSTRACT

OBJECTIVES: The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC. METHODS: Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. RESULTS: Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN. CONCLUSIONS: Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/surgery , Nivolumab/adverse effects , Ipilimumab/adverse effects , Kidney Neoplasms/drug therapy , Kidney Neoplasms/surgery , Cytoreduction Surgical Procedures/adverse effects , Cytoreduction Surgical Procedures/methods , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Nephrectomy/methods
17.
Urol Int ; 107(3): 321-326, 2023.
Article in English | MEDLINE | ID: mdl-36731453

ABSTRACT

Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.


Subject(s)
Carcinoma, Renal Cell , Kidney Failure, Chronic , Kidney Neoplasms , Male , Humans , Aged , Axitinib/therapeutic use , Axitinib/adverse effects , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Retrospective Studies , Renal Dialysis , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy
18.
Jpn J Clin Oncol ; 53(6): 522-529, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36828781

ABSTRACT

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.


Subject(s)
Lung Neoplasms , Prostatic Neoplasms , Small Cell Lung Carcinoma , Male , Humans , Cisplatin/therapeutic use , Etoposide/therapeutic use , Carboplatin , Lung Neoplasms/pathology , Retrospective Studies , Small Cell Lung Carcinoma/pathology , Treatment Outcome , Prostatic Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
19.
Anticancer Res ; 43(2): 841-847, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36697079

ABSTRACT

BACKGROUND/AIM: Increasing availability of effective treatment options for metastatic renal cell carcinoma (mRCC) has highlighted the importance of identifying predictors of treatment response. Although PD-L1 expression in renal cancer has been reported as a predictor of treatment response and prognosis, its assessment by immunohistochemistry is invasive and difficult to perform repeatedly. Soluble PD-L1 (sPD-L1) has recently been proposed as a predictive biomarker for several tumour types. Therefore, we evaluated sPD-L1 levels in patients with mRCC treated with nivolumab and investigated its association with treatment response. PATIENTS AND METHODS: We performed a prospective single-arm study in patients with mRCC treated with nivolumab as second line or later therapy. We measured serum sPD-L1 before and during treatment, classified patients based on baseline values (sPDL1 ≥0.23 ng/ml vs. <0.23 ng/ml) and compared outcomes between the two groups. RESULTS: A total of 43 patients with mRCC were included in this study, with 17 (39.5%) classified as low sPD-L1 and 26 (60.5%) as high sPD-L1. The International Metastatic RCC Database Consortium risk score was significantly poorer in the high sPD-L1 group. The objective response rate was significantly higher (41.2% vs. 7.7%) and overall survival significantly longer (p=0.0323) in the low group compared to the high group. There were no significant differences in progression-free survival between the two groups. CONCLUSION: Our study findings indicate that sPD-L1 might be a predictor of treatment response to nivolumab in patients with mRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Nivolumab/therapeutic use , Carcinoma, Renal Cell/drug therapy , Prognosis , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , B7-H1 Antigen , Prospective Studies
20.
Investig Clin Urol ; 63(4): 415-424, 2022 07.
Article in English | MEDLINE | ID: mdl-35796138

ABSTRACT

PURPOSE: Two methods are used to identify sarcopenia by calculating skeletal muscle area on computed tomography: the skeletal muscle index (SMI) and the psoas muscle index (PMI). Programmed death (PD)-1 inhibitors are helpful in treating metastatic renal cell carcinoma (mRCC). However, there remains insufficient information regarding a clear and easy-to-use biomarker for predicting the response to PD-1 inhibitors in patients with mRCC. Therefore, we investigated the influence of sarcopenia on clinical outcomes in patients with mRCC undergoing treatment with nivolumab. MATERIALS AND METHODS: This study evaluated 96 patients with RCC who received nivolumab. The SMI and PMI were calculated for each patient and normalized for stature by use of the following formulas: SMI (cm²/m²)=([skeletal muscle cross-sectional area at the level of L3]/[height]²) and PMI (cm²/m²) = ([left-right sum of the psoas muscle areas at the level of L3]/[height]²). The relationship of the clinical variables with progression-free survival and overall survival (OS) was examined using a Cox proportional hazards model. RESULTS: According to the SMI-based definition of sarcopenia, 74.0% of patients had sarcopenia. However, according to the PMI-based definition of sarcopenia, only 34.3% of patients were diagnosed with sarcopenia. Multivariate analysis identified sarcopenia based on PMI (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.04-7.26; p<0.001) and International Metastatic RCC Database Consortium poor risk status (HR, 1.90; 95% CI, 1.03-3.50; p=0.041) as significant and independent prognostic factors of OS. CONCLUSIONS: PMI-based sarcopenia is a significant prognostic factor for OS in patients with RCC who receive nivolumab therapy.


Subject(s)
Antineoplastic Agents, Immunological , Carcinoma, Renal Cell , Kidney Neoplasms , Nivolumab , Sarcopenia , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Prognosis , Psoas Muscles/diagnostic imaging , Psoas Muscles/pathology , Retrospective Studies , Sarcopenia/complications , Sarcopenia/diagnostic imaging
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