Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line. METHODS: A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first. RESULTS: Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002). CONCLUSION: Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.

Hyperprogressive disease in advanced cancer patients treated with nivolumab: a case series study.

The aim of this retrospective study was to detail the main clinicopathological characteristics of advanced cancer patients exhibiting hyperprogressive disease (HPD) during immune checkpoint inhibitor (ICI) nivolumab as second- or third-line treatment. A cohort of patients starting second or third-line nivolumab for advanced cancer from 2016 to 2018 was identified from our institution IRB approved and prospectively collected registry. HPD was defined as at least two-fold increase in the tumor growth rate (TGR) during immunotherapy compared to TGR during the preimmunotherapy period. Overall, 47 patients were eligible for this analysis. HPD was observed in three patients (6%) with metastatic lung adenocarcinoma, metastatic urothelial transitional carcinoma, and metastatic hepatocellular carcinoma, respectively. These three patients showed a rapid clinical deterioration and survived less than 3.5 months from immunotherapy onset. Their chief preimmunotherapy characteristics were: age < 75 years, ≥2 metastatic sites, programmed death-ligand 1 < 50%, neutrophil-to-lymphocyte ratio > 3, and elevated lactate dehydrogenase. The results of the current study seem to reinforce the hypothesis that in some cases immunotherapy promotes a dramatic increase of TGR and may suggest possible clinical predictors of HPD during nivolumab.

Feasibility of modified docetaxel, oxaliplatin, capecitabine followed by capecitabine as maintenance chemotherapy as first-line therapy for patients with metastatic gastric or gastroesophageal cancer.

The aim of this study was to evaluate the efficacy and safety of modified docetaxel, oxaliplatin, capecitabine (DOC) combination chemotherapy, followed by maintenance capecitabine as first-line therapy for patients with metastatic gastric or gastroesophageal junction (GEJ) cancer. Treatment consisted of docetaxel 35 mg/m (days 1-8), l-OHP 85 mg/m (day 1), and capecitabine 750 mg/m twice daily (days 1-14), every 3 weeks. After six cycles of DOC, patients who did not progress received maintenance treatment with three-weekly capecitabine 1000 mg/m twice daily (days 1-14), until disease progression or unacceptable toxicity. Six-month disease control rate (DCR) was the primary endpoint and overall survival (OS), progression-free survival (PFS) and safety were the secondary endpoints. The Kaplan-Meier method was applied to estimate OS and PFS. Between July 2014 and September 2017, 37 patients with metastatic gastric or GEJ cancer were enrolled at our institution. Upon completion of the DOC regimen, 35 patients (94.5%) received capecitabine as maintenance chemotherapy for a median of 7 cycles (range, 3-14 cycles). The six-month DCR was 83.7% [95% confidence interval (CI), 71.8-95.6%], median PFS was 8.2 months (95% CI, 6.3-9.8 months), and median OS was 14.4 months (95% CI, 11.7-18.6 months). During DOC chemotherapy, the most common grade 3-4 adverse events were neutropenia (29.7%), anemia (10.8%), and diarrhea (10.8%). During maintenance treatment, toxicity was sporadic and mainly of grade 1-2. Modified DOC followed by capecitabine as maintenance chemotherapy seems to be an active and well tolerated first-line treatment strategy for patients with metastatic gastric and GEJ cancer.

A case of eribulin-induced regression of liposarcoma of the left funiculus in a heavily pretreated patient.

We report the case of a heavily pretreated male subject affected by left funiculus liposarcoma and successfully treated with eribulin mesylate. After three surgical interventions, radiotherapy on the lesion of the penile bulb for satellite nodules and an epirubicin + ifosfamide chemotherapy treatment for six cycles, eribulin was administered at the dose of 1.1 mg/m2 on days 1 and 8, every 3 weeks for a total of nine cycles. A significant reduction of the lesions was achieved after four cycles of therapy, with a good profile of tolerability.

Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC).

BACKGROUND: Currently, there is no universally accepted prognostic classification for patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT). Subgroup analyses demonstrated that pts with low volume (LV), per CHAARTED trial definition, mHSPC, and those who relapse after prior local therapy (PLT) have longer overall survival (OS) compared to high volume (HV) and de-novo (DN), respectively. Using a hospital-based registry, we aimed to assess whether a classification based on time of metastatic disease (PLT vs DN) and disease volume (LV vs HV) are prognostic for mHSPC pts treated with ADT. METHODS: A retrospective cohort of consecutive patients with mHSPC treated with ADT between 1990 and 2013 was selected from the prospectively collected Dana-Farber Cancer Institute database and categorized as DN or PLT and HV or LV, at time of ADT start. Primary and secondary endpoints were OS and time to castration-resistant prostate cancer (CRPC), respectively, which were measured from date of ADT start using Kaplan-Meier method. Multivariable Cox proportional hazards models using known prognostic factors was used. RESULTS: The analytical cohort consisted of 436 patients. The median OS and time to CRPC for PLT/LV were 92.4 (95%CI: 80.4-127.2) and 25.6 (95%CI: 21-35.7) months and 43.2 (95%CI: 37.2-56.4) and 12.2 (95%CI: 9.8-14.8) months for DN/HV, respectively, whereas intermediate values were observed for PLT/HV and DN/LV. A robust gradient for both outcomes was observed (Trend test P < 0.0001) in the four groups. In a multivariable analysis, DN presentation, HV, and cancer-related pain were independent prognostic factors. CONCLUSIONS: In our hospital-based registry, time of metastatic presentation and disease volume were prognostic for mHSPC pts treated with ADT. This simple prognostic classification system can aid patient counseling and future trial design.

Prostate cancer: Developing novel approaches to castration-sensitive disease.

Although androgen-deprivation therapy (ADT) remains the mainstay of castration-sensitive prostate cancer (CSPC) therapy, the disease's heterogeneity and the limited duration of the response have chaperoned the introduction of chemotherapy and the investigation of novel hormonal targeted agents in this setting. Combinations of ADT plus chemotherapy or novel hormonal therapies are being tested at various stages of CSPC with promising results. Furthermore, immunotherapy and experimental drugs are also being actively investigated in this setting. Intriguing multimodality strategies, chiefly deployed for early-stage disease with the aim of maximizing the efficacy and duration of the response, are being explored and may become valid therapeutic options in the future. Ultimately, striking a balance between the clinical gains of these combinations and possibly increased toxicity and reduced quality of life will be necessary. The development of precision medicine and accurate biomarkers is fundamental to progress. Cancer 2017;29-42. © 2016 American Cancer Society.

Targeted Therapies for Prostate Cancer.

New therapies for prostate cancer have emerged over the past three years. Nevertheless, none of these agents is curative, and unfortunately, patients often ultimately develop resistance to these agents. Therefore, the development of innovative and effective therapies that overcome these resistances is necessary. Unfortunately, the results of a phase III trial evaluating docetaxel in combination with targeted therapies demonstrated no difference in survival. Moreover, scarce data on the combination of a targeted therapy with new agents are currently available. New trials are investigating these possible combination treatments; the results of these (on-going) clinical studies are awaited.

Three-weekly oxaliplatin combined with gemcitabine and capecitabine in the first-line treatment of patients with advanced biliary tract cancer.

The primary objective of this study was to determine the activity and safety of 3-weekly oxaliplatin combined with gemcitabine and oral capecitabine in the first-line treatment of advanced biliary tract cancer. Treatment consisted of intravenous oxaliplatin 100 mg/m every 3 weeks combined with intravenous gemcitabine 1000 mg/m on days 1 and 8 and oral capecitabine 1500 mg/m 14 days on 21 in two divided doses. Treatment was administered until progressive disease, unacceptable toxicity, or patient refusal. Thirty-seven patients were enrolled: eight patients had Eastern Cooperative Oncology Group 2 performance status at presentation. The overall response rate was 35.1% [95% confidence interval (CI): 20.2-52.5%] and the disease control rate was 72.9%. The median progression-free survival was 9.4 months (95% CI: 4.1-12.2 months) and the median overall survival was 13.8 months (95% CI: 7.7-17.1 months). There were no grade 4 toxicities. Grade 3 neutropenia occurred in 13.5% of patients and grade 3 thrombocytopenia in 10.8%. The present study suggests that 3-weekly oxaliplatin combined with gemcitabine and oral capecitabine is an active and well-tolerated chemotherapy regimen in the first-line treatment of metastatic biliary tract cancer.

Carboplatin, methotrexate, vinblastine, and epirubicin (M-VECa) as salvage treatment in patients with advanced bladder cancer: a phase II study.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

Tolerability of cabazitaxel in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and abiraterone acetate: a single-institution experience.

Both abiraterone acetate (AA) and cabazitaxel (Cbz) have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel (D). Although no standard sequencing has been established as yet, Cbz has recently been proven to be active after AA. However, to date, few data are available on its safety in this setting. Therefore, the primary endpoint of this study was to investigate Cbz tolerability in mCRPC patients treated previously with D and AA. From April 2011 to the present, 43 mCRPC patients received AA after D at our institution. Of these, 22 patients were subsequently treated with Cbz and were evaluable for toxicity in the present retrospective study. Cbz was administered at a dose of 25 mg/m plus 10 mg oral prednisone every 3 weeks. Adverse events (AEs) were reported using the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. Despite the advanced stage of disease and frailty of our study population, there were no unexpected side effects. The most common AEs were hematologic. Neutropenia was observed in nine (40.9%) patients and of grade≥3 in six (27.2%). No febrile neutropenia occurred. The most common nonhematologic AEs were diarrhea and asthenia, reported in eight (36.3%) and in five (22.7%) patients, respectively. In this setting, Cbz toxicity seems to be manageable and comparable with second-line Cbz. Therefore, our results seem to support the safety of Cbz as a third-line treatment for mCRPC patients.

Maintenance treatment with oral cyclophosphamide and bevacizumab in patients with recurrent epithelial ovarian cancer.

AIM: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer. PATIENTS & METHODS: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred. RESULTS: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild. CONCLUSION: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatments for patients with metastatic castration-resistant prostate cancer: an analysis of 22 trials.

The aim of this study was to determine the correlation between PSA response rate (PSA RR) and overall survival (OS) and identify PSA RR as a potential surrogate for OS, in docetaxel-based first-line treatments for castration-resistant prostate cancer (CRPC). Trials of first-line regimens with docetaxel for patients with metastatic CRCP published between 2004 and 2013 were identified, and data were evaluated statistically in order to investigate the correlation between PSA RR and OS. A total of 22 trials were identified and included in our analysis, for a total of 7,677 patients. In addition, we divided all the trails and arms of the randomized trials in two subgroups, the first one composed only of docetaxel (D) plus prednisone (P) regimens (standard therapy) and the second one composed of all D + other drug combinations (D combinations). Analysing all the trials and arms as a single unit, we found a statistically significant correlation between PSA RR and OS, with Spearman's rank correlation coefficient ρ = 0.50 (95% confidence interval (CI), 0.47 to 0.88) (P = 0.003). Also evaluating the standard therapy group, we found a statistically significant correlation between PSA RR and OS, with Spearman's ρ = 0.65 (95% CI, 0.38 to 0.70) (P = 0.02). However, when we assessed the D combination group, we found Spearman's rank correlation coefficient decreased (ρ = 0.42) (95% CI, 0.28 to 0.80) and resulted nonstatistically significant (P = 0.06). In conclusion, we found a statistically significant correlation between PSA RR and OS. The usage of PSA RR as a surrogate marker for OS in metastatic CRPC patients treated with D-based first-line regimens may be appropriate only in the D + P combination.

Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer.

The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.

Cell-Free DNA: Unveiling the Future of Cancer Diagnostics and Monitoring.

As we conclude this Special Issue of 21 published articles dedicated to cell-free DNA (cfDNA) as a prognostic and predictive biomarker in solid cancers, we find ourselves gazing at a vibrant landscape of research on cfDNA [...].

Gene Signature for Predicting Metastasis in Prostate Cancer Using Primary Tumor Expression Profiles.

Prostate cancer (PCa) is currently the most commonly diagnosed cancer and second leading cause of cancer-related death in men in the United States. The development of metastases is associated with a poor prognosis in PCa patients. Since current clinicopathological classification schemes are unable to accurately prognosticate the risk of metastasis for those diagnosed with localized PCa, there is a pressing need for precise and easily attainable biomarkers of metastatic risk in these patients. Primary tumor samples from 1239 individuals with PCa were divided into development (n=1000) and validation (n=239) cohorts. In the development cohort, we utilized a meta-analysis workflow on retrospective primary tumor gene expression profiles to identify a subset of genes predictive of metastasis. For each gene, we computed Hedges' g effect size and combined their p-values using Fisher's combined probability test. We then adjusted for multiple hypothesis testing using the Benjamini-Hochberg method. Our developed gene signature, termed Meta-Score, achieved a robust performance at predicting metastasis from primary tumor gene expression profiles, with an AUC of 0.72 in the validation cohort. In addition to its robust predictive power, Meta-Score also demonstrated a significant prognostic utility in two independent cohorts. Specifically, patients with a higher risk-score had a significantly worse metastasis-free survival and progression-free survival compared to those with lower score. Multivariate cox proportional hazards model showed that Meta-Score is significantly associated with worse survival even after adjusting for Gleason score. Our findings suggest that our primary tumor transcriptional signature, Meta-Score, could be a valuable tool to assess the risk of metastasis in PCa patients with localized disease, pending validation in large prospective studies. Author Summary: Metastasis is the leading cause of death in patients diagnosed with prostate cancer (PCa), underscoring the need for reliable prediction tools to forecast the risk of metastasis at an early stage. Here, we utilize the gene expression profiles of 1,000 unique primary tumors from patients with localized PCa to develop a gene signature capable of predicting metastasis. Our signature, termed Meta-Score, comprises forty-five genes that can accurately distinguish primary tumor with high propensity for metastasis across different patient cohorts. Notably, Meta-Score maintained its robust predictive performance in an internal validation cohort of comprising primary tumor samples from 239 patients. In addition to its robust predictive performance, Meta-Score demonstrates a significant association with survival, independent of Gleason score in two independent patient cohorts, underscoring its prognostic utility. Taken together, Meta-Score is a robust risk-stratification tool that can be leveraged to identify patients at high-risk of metastasis and unfavorable survival using their primary tumor gene expression profiles.

Intensification Approaches and Treatment Sequencing in Metastatic Castration-resistant Prostate Cancer: A Systematic Review.

BACKGROUND AND OBJECTIVE: Recently, research on treatment intensification has gathered momentum, and three novel therapy combinations were approved for metastatic castration-resistant prostate cancer (mCRPC). This systematic review summarizes the current and emerging evidence around intensified strategies for mCRPC and provides guidance for an ideal therapeutic sequencing. METHODS: Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines were followed to perform this review. PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, and major international societies' online proceedings were searched comprehensively until May 15, 2024, for terms related to treatment intensification and sequencing for mCRPC. KEY FINDINGS AND LIMITATIONS: Overall, 28 clinical trials and 24 ongoing studies of intensification treatments were included in this review. Algorithms of optimal sequencing of approved treatments for mCRPC were outlined according to the use of androgen receptor pathway inhibitors (ARPIs) with or without docetaxel for earlier disease states. In first line, poly(ADP-ribose) polymerase inhibitor + ARPI combinations improve radiographical progression-free survival (rPFS), particularly for those with BRCA1/2 alterations. The AKT inhibitor combination of ipatasertib + abiraterone extends rPFS in those with PTEN loss or PIK3CA/AKT1/PTEN alterations. In those with two or more risk factors for early progression on enzalutamide, radionuclide 177-Lu-PSMA-617 + enzalutamide prolongs progression-free survival. Ongoing research of intensified approaches for mCRPC, and available and potential predictive and prognostic biomarkers are discussed. CONCLUSIONS AND CLINICAL IMPLICATIONS: Recent approvals and ongoing investigations of single agents and intensification approaches will keep transforming the mCRPC treatment landscape. Improvement of patient profiling applying recognized genomic, molecular, and clinical predictive and prognostic indicators is fundamental to optimize sequential use of available therapies.

Outcomes of First-Line Abiraterone Acetate or Enzalutamide for Older Adults With Metastatic Castration-Resistant Prostate Cancer According to Use of Upfront Docetaxel for Metastatic Castration-Sensitive Prostate Cancer in an International Multicenter Registry: A SPARTACUSS-Meet-URO 26 Study.

BACKGROUND: Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged ≥ 75 is challenging due to limited data. Regardless of age, in real-world clinical practice, most mCRPC still derive from failure of androgen deprivation therapy (ADT) with or without docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC). As abiraterone acetate plus prednisone (AA) and enzalutamide (Enza) are common first-line treatments for mCRPC. The impact of prior use of D for mCSPC on the efficacy and safety of AA or Enza in this older population remains unclear. METHODS: A cohort of patients aged ≥ 75 years starting AA or Enza as first-line therapy for mCRPC from January 2015 to April 2019 was identified from the registries of 10 institutions. Patients were categorized into 2 groups based on previous use of D for mCSPC. Primary endpoints were cancer-specific survival (CSS) from AA or Enza start, CSS from ADT onset, and safety. We used Kaplan-Meier method to estimate the endpoints distribution, including median values with 95% confidence intervals (95% CI). RESULTS: Of the 337 patients identified, 24 (7.1%) received ADT+D and 313 (92.9%) received ADT alone for mCSPC. Median follow-up from AA/Enza start was 18.8 months. Median CSS from ADT or AA/Enza was not significantly different between ADT+D and ADT alone cohorts (71.9 vs. 52.7 months, P = .97; 25.4 vs. 27.2 months, P = .89, respectively). No statistically significant difference in adverse events (AEs) of any grade rate (58.3% vs. 52.1%, respectively; P = .67) or grade ≥ 3 (12.5% vs. 15.7%, respectively; P = 1.0) was found between ADT+D and ADT alone cohorts. CONCLUSIONS: Despite the innate limitations of a retrospective design and relatively small size of the ADT+D cohort, this analysis suggests that elderly men receiving AA or Enza as first-line therapy for mCRPC have similar survival outcomes and tolerability, regardless of previous D for mCSPC.

Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer.

Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.

Bone Metastases in Renal Cell Carcinoma: Impact of Immunotherapy on Survival.

Background/Aim: We performed a multicenter retrospective observational study to investigate the impact of immune checkpoint inhibitors (ICIs) on the survival of patients with bone metastases (BMs) from renal cell cancer (RCC). Patients and Methods: A total of 98 patients with metastatic RCC (mRCC) treated with ICIs were retrospectively enrolled. All patients received standard treatments with nivolumab alone or in combination with ipilimumab from December 2015 to March 2022. The primary endpoint was median overall survival (OS). Results: Forty-three patients (44%) had radiological evidence of BMs. No statistically significant difference in OS was reported between the BM population and the entire population (p=0.254). Conclusion: Our study suggests some degree of ICI activity to treat patients with BMs from RCC, historically associated with a poorer prognosis.

Clinical outcomes of volume of disease on patients receiving enzalutamide versus abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients. Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA versus Enza for mCRPC. Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints. Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1-62.2 months] versus AA (51.6 months; 95% CI, 42.6-60.6 months; p = 0.003). Consistently, those with LV receiving Enza showed increased rPFS (40.3 months; 95 CI, 25.0-55.7 months) than those having AA (22.0 months; 95% CI, 18.1-26.0 months; p = 0.004). No significant difference in OS or rPFS was observed in those with HV treated with AA versus Enza (p = 0.51 and p = 0.73, respectively). In multivariate analysis of patients with LV, treatment with Enza was independently associated with better prognosis than AA. Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC.