Schlafen 11 further sensitizes BRCA-deficient cells to PARP inhibitors through single-strand DNA gap accumulation behind replication forks.

The preferential response to PARP inhibitors (PARPis) in BRCA-deficient and Schlafen 11 (SLFN11)-expressing ovarian cancers has been documented, yet the underlying molecular mechanisms remain unclear. As the accumulation of single-strand DNA (ssDNA) gaps behind replication forks is key for the lethality effect of PARPis, we investigated the combined effects of SLFN11 expression and BRCA deficiency on PARPi sensitivity and ssDNA gap formation in human cancer cells. PARPis increased chromatin-bound RPA2 and ssDNA gaps in SLFN11-expressing cells and even more in cells with BRCA1 or BRCA2 deficiency. SLFN11 was co-localized with chromatin-bound RPA2 under PARPis treatment, with enhanced recruitment in BRCA2-deficient cells. Notably, the chromatin-bound SLFN11 under PARPis did not block replication, contrary to its function under replication stress. SLFN11 recruitment was attenuated by the inactivation of MRE11. Hence, under PARPi treatment, MRE11 expression and BRCA deficiency lead to ssDNA gaps behind replication forks, where SLFN11 binds and increases their accumulation. As ovarian cancer patients who responded (progression-free survival >2 years) to olaparib maintenance therapy had a significantly higher SLFN11-positivity than short-responders (<6 months), our findings provide a mechanistic understanding of the favorable responses to PARPis in SLFN11-expressing and BRCA-deficient tumors. It highlight the clinical implications of SLFN11.

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

Real-world treatment trends for patients with advanced prostate cancer and renal cell carcinoma and their cost-a survey in Japan.

BACKGROUND: Advanced (Stage IV) prostate and renal cancer have poor prognosis, and several therapies have been developed, but many are very costly. This study investigated drug regimens used in patients with untreated Stage IV prostate cancer and renal cell carcinoma and calculated the monthly cost of each. METHODS: We surveyed first-line drugs administered to patients with untreated Stage IV prostate cancer and renal cancer at Japan Clinical Oncology Group affiliated centers from April 2022 to March 2023. Drug costs were calculated according to drug prices in September 2023. Individual drug costs were calculated or converted to 28-day costs. RESULTS: A total of 700 patients with untreated Stage IV prostate cancer were surveyed. Androgen deprivation therapy + androgen receptor signaling inhibitor was the most common regimen (56%). The cost of androgen deprivation therapy + androgen receptor signaling inhibitor was 10.6-30.8-fold compared with conventional treatments. A total of 137 patients with Stage IV renal cancer were surveyed. Among them, 91% of patients received immune-oncology drug-based regimen. All patients received treatments with a monthly cost of ≥500 000 Japanese yen, and 80.4% of patients received treatments with a monthly cost of ≥1 million Japanese yen, of combination treatments. The cost of immune-oncology drug-based regimen was 1.2-3.1-fold that of TKI alone. CONCLUSION: To the best of our knowledge, this is the first report of a survey of first-line drug therapy in untreated Stage IV prostate cancer and renal cell carcinoma stratified by age and treatment costs. Our results show that most Japanese patients received state-of-the-art, effective treatments with high financial burden.

Oxidative stress in peroxisomes induced by androgen receptor inhibition through peroxisome proliferator-activated receptor promotes enzalutamide resistance in prostate cancer.

Androgen receptor (AR)-targeting therapy induces oxidative stress in prostate cancer. However, the mechanism of oxidative stress induction by AR-targeting therapy remains unclear. This study investigated the mechanism of oxidative stress induction by AR-targeting therapy, with the aim to develop novel therapeutics targeting oxidative stress induced by AR-targeting therapy. Intracellular reactive oxygen species (ROS) was examined by fluorescence microscopy and flow cytometry analysis. The effects of silencing gene expression and small molecule inhibitors on gene expression and cytotoxic effects were examined by quantitative real-time PCR and cell proliferation assay. ROS induced by androgen depletion co-localized with peroxisomes in prostate cancer cells. Among peroxisome-related genes, PPARA was commonly induced by AR inhibition and involved in ROS production via PKC signaling. Inhibition of PPARα by specific siRNA and a small molecule inhibitor suppressed cell proliferation and increased cellular sensitivity to the antiandrogen enzalutamide in prostate cancer cells. This study revealed a novel pathway by which AR inhibition induced intracellular ROS mainly in peroxisomes through PPARα activation in prostate cancer. This pathway is a promising target for the development of novel therapeutics for prostate cancer in combination with AR-targeting therapy such as antiandrogen enzalutamide.

Importance of 3ß-hydroxysteroid dehydrogenases and their clinical use in prostate cancer.

Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3ß-hydroxysteroid dehydrogenases (3ßHSDs) play critical roles in extragonadal androgen synthesis, especially 3ßHSD1. Increased expression of 3ßHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3ßHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3ßHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3ßHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3ßHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.

Immature stroma and high infiltration of CD15+ cells are predictive markers of poor prognosis in different subsets of patients with pancreatic cancer.

Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along with their association with histological findings remains unclear, especially in patients receiving preoperative chemotherapy. We aimed to explore the therapeutic strategies for patients with PDAC with poor prognosis after receiving chemotherapy based on histological and immunological microenvironmental classifications. We investigated the correlation between the prognosis and histological immune microenvironmental factors of patients who initially underwent surgery (n = 100) and were receiving gemcitabine plus nab-paclitaxel (GEM + nabPTX) as preoperative chemotherapy (n = 103). Immune profiles were generated based on immune cell infiltration into the tumor, and their correlation with patient outcomes and histological features was analyzed. Tumor-infiltrating neutrophils (TINs) were identified as independent poor prognostic factors using multivariate analysis in both surgery-first and preoperative chemotherapy groups. The patients were further classified into four groups based on immune cell infiltration into the tumor. Patients with high CD15 infiltration into the tumor and immature stroma at the cancer margins showed the worst prognosis in the preoperative chemotherapy group. The analysis of mRNA expression and immunohistochemical features revealed that CXCR2, the receptor for CXCL8, was correlated with disease-free and overall survival. We inferred that patients with immature stroma at the margins and high infiltration of CD15+ neutrophils within the tumor showed the worst prognosis and they could particularly benefit from treatment with inhibitors targeting CXCR2 or CXCL8.

Prognostic value of preoperative geriatric nutritional risk index in intrahepatic cholangiocarcinoma after hepatectomy: a single­center retrospective cohort study.

AIM: Patients with malignant tumors are prone to develop nutritional disorders. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for assessing the nutritional status. This study was performed to evaluate whether the preoperative GNRI can serve as a prognostic factor in patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative surgery. METHODS: This study included 123 consecutive patients with ICC who were treated with curative surgery. Kaplan-Meier analysis was performed to calculate the recurrence-free survival (RFS) and overall survival (OS), and Cox regression analysis was used to evaluate prognostic factors. RESULTS: Of the 123 patients, 82 were male and 41 were female. The median age of the patients was 70 years, and the median follow-up period was 37.0 months (interquartile range, 16.2-71.7 months). The patients were classified by the median GNRI into a low GNRI group (GNRI < 105) and high GNRI group (GNRI ≥ 105). The patients in the low GNRI group had a significantly poorer prognosis in terms of RFS and OS than the patients in the high GNRI group (RFS, p = 0.0201; OS, p < 0.0001). Lymph node metastasis [hazard ratio (HR), 4.66; 95% confidence interval (CI), 2.46-8.85], postoperative complications (HR, 2.38; 95% CI, 1.32-4.31), and a low GNRI (HR, 2.53; 95% CI, 1.42-4.50) were independent poor prognostic factors for OS. CONCLUSION: The GNRI may be a useful prognostic indicator in patients with ICC undergoing curative hepatectomy.

Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy to the prostate.

PURPOSE: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. METHODS: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. RESULTS: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135-226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. CONCLUSIONS: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is a standard approach for management of locally advanced esophageal squamous cell carcinoma (ESCC). Patients who do not respond well to NAC have a poor prognosis. Despite extensive research, the mechanisms of chemoresistance in ESCC remain largely unknown. Here, we established paired tumor organoids-designated as PreNAC-O and PostNAC-O-from one ESCC patient before and after NAC, respectively. Although the two organoids did not exhibit significant differences in proliferation, morphology or drug sensitivity in vitro, the tumorigenicity of PostNAC-O in vivo was significantly higher than that of PreNAC-O. Xenografts from PreNAC-O tended to exhibit keratinization, while those from PostNAC-O displayed conspicuous necrotic areas. The tumorigenicity of PostNAC-O xenografts during the chemotherapy was comparable to that of PreNAC-O without treatment. Furthermore, the gene expression profiles of the xenografts suggested that expression of genes involved in the EMT and/or hypoxia response might be related to the tumorigenicity of PostNAC-O. Our data suggested that the tumorigenicity of residual cancer had been enhanced, outweighing the effects of chemotherapy, rather than being attributable to intrinsic chemoresistance. Further studies are required to clarify the extent to which residual cancers share a common mechanism similar to that revealed here.

Long-term Recurrence Rates of Low-risk Non-muscle-invasive Bladder Cancer-How Long Is Cystoscopic Surveillance Necessary?

BACKGROUND: While low-risk non-muscle-invasive bladder cancer (LR-NMIBC) has a low propensity to progress, the risk of recurrence remains high (50% within 4 yr). Guidelines recommend cystoscopic surveillance after resection, but the necessary duration of follow-up is debated. OBJECTIVE: To determine the risk of recurrence beyond 5 yr after diagnosis in patients with LR-NMIBC, and to identify risk factors of recurrence. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective observational study, patients who received their first transurethral bladder tumor resection before 2016 for LR-NMIBC were included. Low risk was defined as a primary, solitary, low grade, Ta bladder tumor measuring <3 cm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was determination of the recurrence rates at 1, 2, and 5 yr. The secondary endpoints included overall recurrence-free survival (RFS) and high-risk RFS. A univariate analysis and multivariable logistic regression were performed to assess the risk factors for recurrence over the study period. RESULTS AND LIMITATIONS: The median age of the 577 patients was 70.9 yr, and 126 (21.8%) patients were female. The median follow-up was 69.6 (interquartile range: 58.4) mo, and recurrence was observed in 236 (40.9%) patients. The 1-, 2-, and 5-yr RFS rates were 81.6% (95% confidence interval 78.4-84.9), 72.4% (68.7-76.3), and 59.2% (55-63.8), respectively. Recurrence after 5 yr was observed in 13.1% (28/213). High-risk recurrence, defined as the first recurrence of a high-grade and/or ≥T1 tumor, occurred in 6.2% (36/579) overall and 2.8% (6/213) after 5 yr. The lack of a single postoperative dose of chemotherapy and tumor size >2 cm were prognostic factors of recurrence. CONCLUSIONS: The risk of recurrence in patients with LR-NMIBC decreases progressively after the 1st year and remains low beyond 5 yr. Discontinuation of endoscopic surveillance after 5 yr in patients with LR-NMIBC can be discussed. Treatment with postoperative chemotherapy and tumor size <2 cm may be relevant variables to identify patients who will benefit from cystoscopic follow-up as short as 12 mo. PATIENT SUMMARY: In this study, we observed that 13% of patients who did not have a recurrence during the first 5 yr following the diagnosis of low-risk non-muscle-invasive bladder cancer will recur after this time point. Discontinuation of cystoscopic surveillance can be discussed after 5 yr in these patients.

Obstructive Shock Due to a Crushed Left Atrium and Pulmonary Vein by Pulmonary Artery Intimal Sarcoma Successfully Treated with Pulmonary Vein Stenting.

A 46-year-old patient who had undergone right pneumonectomy for pulmonary artery intimal sarcoma presented with hypoxemia. The recurrent sarcoma in the mediastinum revealed external compression to the left pulmonary veins (PVs), leading to obstructive shock and cardiac arrest. Venous artery extracorporeal membrane oxygenation (VA-ECMO) was initiated; however, withdrawal was difficult, and the patient's survival seemed hopeless. However, the patient's condition improved with stenting for the compressed PV; therefore, VA-ECMO was discontinued, and he was discharged on foot. This is the first case report of obstructive shock due to critical PV stenosis caused by compression of a malignant tumor that responded to PV stenting.

Patient vulnerability is associated with poor prognosis following upfront hepatectomy for colorectal liver metastasis.

BACKGROUND: With the rapid aging of populations worldwide, the number of vulnerable patients with liver metastasis from colorectal cancer has increased. This study aimed to examine the association between vulnerability and clinical outcomes in patients with colorectal liver metastasis (CRLM). METHODS: Consecutive 101 patients undergoing upfront hepatectomy for CRLM between 2004 and 2020 were included. The preoperative vulnerability was assessed using the Clinical Frailty Scale (CFS) score ranging from one (very fit) to nine (terminally ill), and frailty was defined as a CFS score of ≥ 4. A multivariable Cox proportional hazard regression model was utilized to investigate associations of frailty with disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Of the 101 patients, 12 (12%) had frailty. Associations between frailty and surgical outcomes, namely, the incidence of 90-day mortality and postoperative complications, were not statistically significant (P > 0.05). In the multivariable analyses, after adjusting for clinical risk scores calculated using six factors (timing of liver metastasis, primary tumor lymph node status, number of liver tumors, size of the largest tumor, extrahepatic metastatic disease, and carbohydrate antigen 19-9 level) to predict recurrence following hepatectomy for CRLM, preoperative frailty was found to be an independent risk factor for DFS (hazard ratio [HR]:2.37, 95% confidence interval [CI] 1.06-4.72, P = 0.036), OS (HR:4.17, 95% CI 1.43-10.89, P = 0.011), and CSS (HR:3.49, 95% CI 1.09-9.60, P = 0.036). CONCLUSION: Preoperative frailty was associated with worse DFS, OS, and CSS after upfront hepatectomy for CRLM. Assessment and improvement of patient vulnerability may provide a favorable prognosis for patients with CRLM.

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab.

INTRODUCTION: Recently, many agents and combinations for metastatic and advanced renal cell carcinoma have been approved. This study aims to highlight the comprehensive differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) and ipilimumab (IPI) plus NIVO based on a real-world big dataset. MATERIAL AND METHODS: We downloaded AE datasets of IPI + NIVO and CAB + NIVO from the Food and Drug Administration Adverse Event Reporting System database. We used the Medical Dictionary for Regulatory Activities to treat each AE as a preferred term and grouped it into the System Organ Class (SOC). We performed logistic regression analyses to compare IPI + NIVO and CAB + NIVO. RESULTS: The incidence rates of 7 types of toxicities were higher for CAB + NIVO than for IPI + NIVO. On the other hand, the incidence rates of 3 types of toxicities were higher for IPI + NIVO than for CAB + NIVO. Serious AEs were higher in patients receiving IPI + NIVO. CONCLUSION: Our findings suggest that both combination therapies presented a disproportionate distribution of toxicities in several SOC. These findings may help clinicians select suitable therapy for the individual and improve the safety profile in patients with advanced renal cell carcinoma receiving NIVO + IPI and NIVO + CAB in a real-world setting.

Comprehensive genomic profiling testing in Japanese castration-resistant prostate cancer patients: results of a single-center retrospective cohort study.

OBJECTIVE: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. METHODS: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. RESULTS: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041). CONCLUSIONS: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option.

Utilization of an Automated Latex Agglutination Turbidity Assay for Assessing Gastric Mucosal Alteration during Helicobacter pylori Infection.

Background/Aims: : A latex agglutination turbidity (LA) assay to test for serum antibodies has been approved in Japan and Korea for mass screening of Helicobacter pylori infection. In this study, we evaluated the LA assay for diagnosing H. pylori infection and predicting gastric mucosal changes in a Mongolian population. Methods: : In total, 484 individuals were classified into H. pylori-positive (n=356) and H. pylori-negative (n=128) groups, as determined by histology and H. pylori culture. Results: : The best cutoff, sensitivity, and specificity values for the LA assay were 18.35 U/mL, 74.2%, and 65.6%, respectively. The LA values in the atrophic gastritis group were statistically higher than those in the other groups (healthy, chronic gastritis, intestinal metaplasia, and gastric cancer, p<0.0001). The cutoff value to distinguish the atrophic gastritis group from the other four groups was 32.0 U/mL, and its area under the curve was 0.673, which was the highest among the E-plate, pepsinogen (PG) I, PG II, and PG I/II ratio tests in our data. The odds ratios for atrophic gastritis determined by the LA assay and PG I test in multiple logistic regression were 2.5 and 1.9, respectively, which were significantly higher than for the other tests. Conclusions: : The LA assay can determine the risk of atrophic gastritis, which in turn is a considerable risk factor for gastric cancer. We propose using this assay in combination with the PG I/II ratio to avoid missing gastric cancer patients who have a low LA value (less than 32.0 U/mL).

Perioperative disabilities in activities of daily living are associated with worse prognosis after hepatectomy for colorectal liver metastasis.

BACKGROUND: The number of vulnerable patients with colorectal liver metastasis (CRLM) has increased. This study aimed to clarify the relationship between perioperative activities of daily living (ADL) and clinical outcomes after hepatectomy for CRLM. METHODS: Consecutive patients undergoing resection of CRLM from 2004 to 2020 were included. Pre- or postoperative ADL was evaluated according to Barthel index (BI) scores, which range from 0 to 100. Higher scores represent greater level of independence in ADL. Pre- or postoperative BI scores of ≤85 were defined as perioperative disabilities in ADL. Multivariable Cox proportional hazard regression models were utilised to estimate adjusted hazard ratios (HRs) and confidence interval (CI). RESULTS: A total of 218 patients were included, 16 (7.3%) revealed preoperative BI scores of ≤85, and 32 (15%) revealed postoperative BI scores of ≤85. In multivariate analyses, the perioperative disabilities in ADL were independently associated with shorter overall survival (HR, 1.96; 95% CI, 1.10-3.31; P = 0.023) and cancer-specific survival (HR, 2.31; 95% CI, 1.29-3.92; P = 0.006). CONCLUSION: Perioperative disabilities in ADL were associated with poor prognosis following hepatectomy for CRLM. Improving preoperative vulnerability and preventing functional decline after surgery may provide a favourable prognosis for patients with CRLM.

Validation of schedules for optimal prostate-specific antigen monitoring after radical prostatectomy.

BACKGROUND: Early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is crucial for early treatment and improving survival outcomes. The optimal prostate-specific antigen (PSA) monitoring remains unclear, and several models have been proposed. We aimed to externally validate four models for optimal PSA monitoring after RP and propose modifications to improve them. METHODS: We reviewed the clinicopathological data of 896 patients who underwent robot-assisted RP between 2009 and 2022. We examined all PSA values and estimated the PSA value for four monitoring schedules at each time point in the virtual follow-up. We defined the ideal PSA for BCR detection between 0.2 and 0.4 ng/mL. RESULTS: During the median follow-up of 21.4 months, 128 (14.3%) patients presented BCR. The original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model detected BCR in 14 (10.9%), three (2.3%), 12 (9.4%), and 11 (8.6%) patients with PSA >0.4 ng/mL. Most patients experienced BCR detected with PSA >0.4 ng/mL during the first year postoperative. The modification of interval within 6 months postoperative avoided BCR detection with PSA >0.4 ng/mL within the first year postoperative in 8/9 (88.9%), 1/2 (50.0%), 5/6 (83.3%), and 4/4 (100%) for the original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model, respectively. CONCLUSION: We validated four models for PSA monitoring after RP to detect BCR and suggested modifications to avoid detections out of the desired range of PSA. These modifications could help to establish an optimal PSA monitoring schedule after RP.

Current status and future perspective of immunotherapy for renal cell carcinoma.

In the last decade, the standard treatment for advanced renal cell carcinoma (RCC) has evolved, mainly driven by the development and approval of immune checkpoint inhibitors (ICIs). Currently, ICI monotherapy and ICI-based combinations with tyrosine kinase inhibitors and targeted therapies against mammalian target of rapamycin or vascular endothelial growth factor have become new standard treatments for first-line and subsequent-line therapies. ICIs play an important role as an adjuvant postoperative therapy, and this field is the subject of active research. Furthermore, ongoing randomized controlled trials are investigating the clinical value of more intense treatments by combining multiple effective treatments for RCC. Additionally, novel biomarkers for prognosis have been investigated. This study reviews the current evidence on immunotherapy as a treatment for RCC patients, randomized controlled trials, and ongoing studies including RCC patients and recent findings, and discusses future perspectives.