Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma.

Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our investigation was to identify a protein panel and the molecular pathways involved in chemotherapy response through a combination of studying proteomics and network enrichment analysis by considering a subset of samples from a clinical setting. Differential mass spectrometry studies were performed on 14 serum samples from patients with heavily pretreated platinum-resistant ovarian cancer who received the FOLFOX-4 regimen as a salvage therapy. The serum was analyzed at baseline time (T0) before FOLFOX-4 treatment, and before the second cycle of treatment (T1), with the aim of understanding if it was possible, after a first treatment cycle, to detect significant proteome changes that could be associated with patients responses to therapy. A total of 291 shared expressed proteins was identified and 12 proteins were finally selected between patients who attained partial response or no-response to chemotherapy when both response to therapy and time dependence (T0, T1) were considered in the statistical analysis. The protein panel included APOL1, GSN, GFI1, LCATL, MNA, LYVE1, ROR1, SHBG, SOD3, TEC, VPS18, and ZNF573. Using a bioinformatics network enrichment approach and metanalysis study, relationships between serum and cellular proteins were identified. An analysis of protein networks was conducted and identified at least three biological processes with functional and therapeutic significance in ovarian cancer, including lipoproteins metabolic process, structural component modulation in relation to cellular apoptosis and autophagy, and cellular oxidative stress response. Five proteins were almost independent from the network (LYVE1, ROR1, TEC, GFI1, and ZNF573). All proteins were associated with response to drug-resistant ovarian cancer resistant and were mechanistically connected to the pathways associated with cancer arrest. These results can be the basis for extending a biomarker discovery process to a clinical trial, as an early predictive tool of chemo-response to FOLFOX-4 of heavily treated ovarian cancer patients and for supporting the oncologist to continue or to interrupt the therapy.

Melphalan as a Promising Treatment for BRCA-Related Ovarian Carcinoma.

INTRODUCTION: Melphalan, as a bifunctional alkylating agent has been shown to be selectively efficient in BRCA-deficient case reports of epithelial ovarian cancer (EOC). The clinical benefit of melphalan on unselected platinum-resistant EOC population and stratified by BRCA status has not been clearly elucidated. We aimed to determine the response to melphalan in patients with recurrent EOC after platinum-based therapy. MATERIAL AND METHODS: This retrospective observational study included patients with recurrent EOC treated with melphalan between February 2007 to July 2020. Eligibility criteria included having a histological confirmation of EOC, previous treatment with carboplatin plus paclitaxel regimens, and disease recurrence during treatment with or within 6 months of the end of the platinum-based chemotherapy. RESULTS: A total of 75 platinum-resistant EOC patients were enrolled. Median age was 69 years (range 41-82). Median of previous therapies before melphalan was 4 (range 1-7). We observed a median follow-up of 32 months (range 1-62), progression-free survival (PFS) and overall survival (OS) of 3.6 months (range 2.9-4.7) and 9.5 months (range 8.0-14.1), respectively. In the whole population, 1 complete response, 6 partial responses and 37 stable diseases were registered with an overall clinical benefit rate of 58.7%. In BRCA1/2 mutant patients, we showed a significant longer PFS compared to BRCA1/2 wild type patients (6.2 versus 2.6 months; hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.10-0.61; p=0.002). Moreover, a trend was seen for BRCA1/2 mutants to have a better OS (25.9 versus 8.0 months; HR 0.38; 95% CI 0.12-1.19; p=0.097). CONCLUSIONS: Our study represents the largest cohort of heavily-pretreated EOC patients receiving melphalan treatment. Here, we report a considerable clinical activity of melphalan chemotherapy, more evident in a subset of BRCA1/2 mutated patients. Prospective studies to validate these findings are warranted.

Post-traumatic stress symptoms in long-term disease-free cancer survivors and their family caregivers.

BACKGROUND: The experience of cancer is highly stressful and potentially traumatic. We assessed the presence of Post-Traumatic Stress Symptoms (PTSS) in long-term cancer survivors and their caregivers, while examining the association between PTSS and clinical, demographic and psychological variables in the long term. METHODS: In this cross-sectional study 212 survivor-family caregiver dyads completed measures of post-traumatic stress symptoms (PTSS) (Impact of Event Scale), depression and anxiety (Hospital Anxiety Depression Scale). Coping strategies, fatigue, cognitive decline, stressful life events and psychopathological history were also assessed among survivors. Data were analyzed using mixed models, accounting both for individual and dyadic effects. RESULTS: Cancer survivors and their caregivers were assessed after a mean of 6 years after treatment. Twenty per cent of survivors and 35.5% of caregivers had possible posttraumatic stress disorder (PTSD), while 23 patients (11.0%) and 33 caregivers (15.6%) had probable PTSD. Among cancer patients, the severity of post-traumatic symptoms was associated with an anxious coping style, previous psychopathology and depression (p < 0.001), whereas among caregivers it was associated with depression and having a closer relationship with patients (p < 0.001). Patients' depression was associated with caregivers' intrusion symptoms. CONCLUSIONS: High levels of cancer-related PTSS were still present several years after treatment in both survivors and caregivers. Psychopathology may derive from complex interactions among coping, previous disorders and between-person dynamics.

Potential Application of Chimeric Antigen Receptor (CAR)-T Cell Therapy in Renal Cell Tumors.

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors. Although the treatment has several advantages over previous T-cell receptor-dependent immunotherapy, it is facing some obstacles in solid tumors such as a hostile tumor microenvironment and on-tumor/off-tumor toxicities. Several strategies are under investigation to overcome these problems, but the approval of CAR-T cell therapy is still some way off. In renal cancer, the significant advantages obtained from immune checkpoint inhibitors represent a good starting point, but the potential nephrological toxicity of CAR-T cell therapy represents an important risk. In this review, we provide the rationale and preliminary results of CAR-T cell therapy in renal cell malignancies.

Enzalutamide for the treatment of nonmetastatic castration-resistant prostate cancer.

INTRODUCTION: Enzalutamide is the first characterized second-generation nonsteroidal androgen receptor inhibitor (ARi). Its efficacy has been established in several clinical trials evaluating its role in different settings of prostate cancer. Recently, enzalutamide has been approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). AREAS COVERED: In this paper, the authors describe the chemical structure and pharmacologic characteristics of enzalutamide, providing a summary of clinical trials evaluating its efficacy and safety in prostate cancer patients. EXPERT OPINION: Enzalutamide adds to the growing arsenal of ARi used in nmCRPC. An improvement in metastasis-free survival was observed with the use of these new treatment options; recently released preliminary data report also an OS benefit. These novel agents are generally well tolerated, but their safety profiles differ slightly. Since head-to-head comparisons between ARi in nmCRPC are lacking, the adverse events profile, as well as drug availability, costs, and considerations on treatment-sequencing, would most likely influence the selection of the individual agent in this setting. Further research is needed to improve treatment selection and clarify many unsolved issues. Abbreviations ARi: nonsteroidal androgen receptor inhibitor; nmCRPC: nonmetastatic castration resistant prostate cancer; ADT: androgen deprivation therapy; OS: overall survival; PSA: prostate specific antigen; FDA: Food and Drug Administration; AR: Androgen Receptor; MFS: metastasis free survival; PSA-DT: PSA doubling time; HR: hazard ratio; CI: confidence interval; AEs: adverse events; mCRPC: metastatic castration resistant prostate cancer; mHSPC: metastatic hormone-sensitive prostate cancer; rPFS: radiographic progression-free survival; OR: odds ratio.

Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress.

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.

Plasma Androgen Receptor in Prostate Cancer.

The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Recently, highly sensitive next-generation sequencing and PCR-based methods for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma were established in cell-free DNA (cfDNA) of patients with castration-resistant prostate cancer (CRPC) treated with different drugs. The study of cfDNA holds great promise for improving treatment in CRPC, especially in the advanced stage of the disease. Recent findings showed the significant association of plasma AR aberrations with clinical outcome in CRPC patients treated with AR-directed therapies, whereas no association was observed in patients treated with taxanes. This suggests the potential for using plasma AR as a biomarker for selecting treatment, i.e., hormone therapy or chemotherapy, and the possibility of modulating taxane dose. In recent years, plasma AR status has also been investigated in association with novel agents, such as 177Lu-PSMA radioligand therapy and PARP inhibitors. This review will focus on AR testing in plasma that may have clinical utility for treatment selection in advanced prostate cancer.

Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer.

BACKGROUND: The purpose of this study was to evaluate the clinical impact of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in terms of the response rate, progression-free/overall survival (PFS/OS) and safety profile in patients with heavily pretreated recurrent epithelial ovarian cancer. METHODS: Clinical data were reviewed in 29 patients who received FOLFOX-4 as more than third-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin, 200 mg/m2 of leucovorin, and bolus 400 mg/m2 on day 1 of 5-fluorouracil, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for 2 consecutive days every 3 weeks. We also compared the efficacy and toxicity of FOLFOX-4 with that of topotecan, a standard treatment, given at a dosage of 1.5 mg/m2 every three weeks in 26 patients. RESULTS: The median age of enrolled patients was 60 years (range 33 to 85). A median of 4 cycles (range 1-17) of FOLFOX-4 were administered. Complete response and partial response were observed in one (3.5%) and 5 (17.2.2%) patients, respectively, while stable disease was reported in 8 (27.6%) patients. Among all patients, grade 3-4 anemia, neutropenia, and thrombocytopenia were observed in 0 (0%), 5 (17.2%), and 3 (10.3%) cases, respectively. Grade 3-4 fatigue was recorded in one (3.4%) patient and diarrhea in 2 (6.9%). Median PFS and OS were 2.8 months [95% confidence interval (CI) 1.7-4.9] and 6.2 months (95% CI 2.4-14.6), respectively. No significant differences in terms of efficacy and toxicity were observed between patients receiving FOLFOX-4 and those treated with topotecan. CONCLUSIONS: The FOLFOX-4 regimen would seem to obtain similar survival rates to those of standard therapy with topotecan in platinum-resistant ovarian cancer. Further randomized trials are warranted to confirm our findings.

Emerging targets in advanced non-small-cell lung cancer.

New therapeutic options in non-small-cell lung cancer have been available through a great in-depth and genomic research, improving preclinical disease patterns and identifying the specific toxicity of target therapy. The multidisciplinary approach, increasingly practiced among clinicians, researchers, pharmaceutical companies and ethics committees has allowed the emergence of a new generation of translational clinical trials and the adoption of new technologies (e.g., point-of-care sequencing), then speeding up the development and trade of these new drugs. Consequently, there is a long list of therapeutic candidates that need to be efficiently evaluated early in the context of Phase I clinical trials. In this review, we discuss some of the key developments and novelties in the main histological groups.

Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

PURPOSE: The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. METHODS: We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. RESULTS: We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). CONCLUSIONS: Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer.

BACKGROUND: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. OBJECTIVE: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. CONCLUSION: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

Immunotherapy for Prostate Cancer: Where We Are Headed.

Prostate cancer is one of the most common malignant neoplasms in men worldwide, and is the fifth cause of cancer-related death. In recent years, a new generation of therapies have been approved for the management of metastatic disease. Moreover, the development of new immunotherapeutic drugs has become a novel frontier for the treatment of several tumor types; to date, numerous studies have investigated their potential activity, including in prostate cancer. In this article, we discuss the role of emerging immunotherapeutic drugs in prostate cancer patients.

Urinary RNA-based biomarkers for prostate cancer detection.

Prostate cancer (PCa) is the commonest malignancy in the male population worldwide. Serum prostate specific antigen (PSA) test is the most important biomarker for the detection, follow-up and therapeutic monitoring of PCa. Defects in PSA specificity have elicited research for new biomarkers to improve early diagnosis and avoid false-positive results. This review evaluates urinary RNA-based biomarkers. Urine is a versatile body fluid for non-invasive biomarker detection in case of urological malignancies. The importance of RNA-based biomarkers has been demonstrated by the current use of PCA3, a long non coding RNA biomarker already approved by the Food and Drugs Administration. Through the years, other urinary RNA biomarkers have been evaluated, including the well-known TMPRSS2:ERG transcript, as well as many messenger RNAs, long non coding RNAs and micro-RNA. Validation of a specific urinary RNA-based marker or an algorithm of different biomarkers levels as diagnostic markers for PCa could be useful to avoid unnecessary prostate biopsies.

Vitamin D status among long-term survivors of testicular cancer.

A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC).We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.

Is polypharmacy an independent risk factor for adverse outcomes after an emergency department visit?

This study aimed at verifying the role of polypharmacy as an independent risk factor for adverse health outcomes in older emergency department (ED) patients. This was a large (n = 2057) sample of older ED patients (≥65 years) participating in an observational cohort study. Polypharmacy and excessive polypharmacy were defined as having 6-9 drug prescriptions and 10 or more drug prescriptions in the last 3 months, respectively. The total number of medication prescriptions was also available. Outcome measures were in-hospital mortality; 30-day ED return; ED revisit, hospital admission, and mortality at 6 months. Logistic and Cox regression models as well as receiver operating characteristic curves using the Youden index and the area under the curve were calculated. Polypharmacy and excessive polypharmacy were present in 624 (30.3 %) and 367 (17.8 %) subjects, respectively. The mean number of prescriptions in the last 3 months was 5.7 (range 0-25) drugs. Polypharmacy and, particularly, excessive polypharmacy were constantly and independently associated with worse outcomes. A cut-off of 6 had the highest value of the Youden Index in predicting the majority of the adverse outcomes considered. Polypharmacy and excessive polypharmacy are independent risk factors for adverse health outcomes after an ED visit. Further studies are needed to clarify whether drug related issues (such as non-compliance, inappropriate or suboptimal prescribing, adverse drug reactions, and drug-drug or drug-disease interactions) or underlying multimorbidity and disease severity, as well as clinical complexity and frailty, are responsible for the negative outcomes associated with polypharmacy.

Impact of Non-Pulmonary Visceral Metastases in the Prognosis and Practice of Metastatic Testicular Germ Cell Tumors.

Non-pulmonary visceral metastases, in bones, brain and liver, represent nearly the 10% of metastatic sites of advanced germ cell tumors and are associated with poor prognosis. This review article summarizes major evidences on the impact of different visceral sites on the prognosis, treatment and clinical outcome of patients with germ cell tumors. The clinic-biological mechanisms by which these metastatic sites are associated with poor clinical outcome remain unclear. The multimodality treatment showed a potential better survival, in particular in patients with relapsed disease. Patients with advanced germ cell tumors with visceral metastases should be referred to centers with high expertise in the clinical management of such disease.

Correlation of Stomatitis and Cutaneous Toxicity With Clinical Outcome in Patients With Metastatic Renal-Cell Carcinoma Treated With Everolimus.

BACKGROUND: In clinical practice, discontinuation or dose reduction of everolimus may be induced not only by grade 3 or 4 toxicities but also by prolonged grade 2 toxicities, such as stomatitis and/or cutaneous toxicity, which share some pathogenetic mechanisms. We assessed the correlation between either everolimus discontinuation or dose reduction induced by stomatitis-cutaneous toxicity events (SCTE) and clinical outcome of patients with metastatic renal-cell cancer (mRCC). PATIENTS AND METHODS: We retrospectively reviewed the clinical data of patients with mRCC treated with everolimus in 2 Italian centers. Clinical evidence of SCTE was evaluated, and corresponding clinical data were reviewed for response and clinical outcome. RESULTS: Seventy-nine mRCC patients treated with everolimus (57 male, 22 female; median age 66 years; range, 44-88 years) were evaluated. SCTE were observed in 20 (25%) of 79 patients at a median of 30.5 days of everolimus treatment (range, 10-270 days). Partial response or stable disease was achieved in 15 (79%) of 19 evaluable patients with SCTE compared to 28 (48%) of 58 with no SCTE (P = .03). At a median follow-up of 19 months, a significant difference was found in the median PFS equal to 7.8 months (95% confidence interval [CI], 2.8-24.4) in SCTE patients versus 4.3 months (95% CI, 2.7-7.5) in non-SCTE patients (P = .029), and in the median OS equal to 30.6 months (95% CI, 19.6-not reached) in SCTE patients versus 13.5 months (95% CI, 9.9-17.7) in non-SCTE patients (P = .0007). CONCLUSION: These data suggest that SCTE may be a predictive marker of favorable outcome in mRCC patients treated with everolimus.

CYP17A1 polymorphisms and clinical outcome of castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: We evaluated the role of single nucleotide polymorphisms in the CYP17A1 gene for predicting clinical outcome in castration-resistant prostate cancer (CRPC) patients treated with abiraterone. METHODS: Sixty-four patients were genotyped for the selected polymorphisms (rs743572, rs10883783, rs17115100 and rs284849) in CYP17A1. We hypothesized that different genotypes could be associated with progression-free survival (PFS) and overall survival (OS). RESULTS: Statistical analyses highlighted no significant associations between these polymorphisms and clinical outcome. However, individuals with the most common TT genotype for rs10883783 had a 3 months' longer PFS than individuals with the TA + AA genotype. CONCLUSIONS: With the limitation of the retrospective study design and the small sample size, the analyzed polymorphisms do not seem to be correlated with clinical outcome of CRPC patients treated with abiraterone.

(18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

PURPOSE: We investigated the role of (18)F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. METHODS: The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50% was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66%) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007). CONCLUSION: This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.