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Introduction: Rare genitourinary tumors are lacking of randomized and observational data. We aimed to describe the clinical characteristics and outcomes of patients with collecting duct carcinoma (CDC) through the Meet-URO 23/I-RARE database., Materials and Methods: We performed a multicentric retrospective-prospective study within the Meet-URO network, enrolling patients from March 2021 (retrospectively up from 2011) until March 2023. The primary objective was to describe the clinical characteristics of patients with CDC, the secondary objectives were to assess the oncological outcomes in terms of relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to treatment., Results: 37 patients with CDC were enrolled. Four patients underwent only surgery, 33 received first-line systemic therapy. Median OS was 22.1 months (95% CI, 8.9-31.9). Median RFS for patients with localized disease at onset (n = 30) was 3.7 months (95% CI, 1.9-12.8), median PFS for first-line treatment was 3.3 months (95% CI, 2.7-9.9), with an ORR of 27%. Female sex and good performance status (PS) were associated with longer PFS (P = .072 and P < .01, respectively) and OS (P = .030 and P = .141, respectively)., Conclusions: Patients with CDC had dismal prognosis, with scarce benefit from the available treatments. Female sex and good PS seemed to be associated with better prognosis., Competing Interests: Disclosure The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC)., Case Presentation: We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response., Conclusions: Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis., (© 2024. The Author(s).)

Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study, we explored the potential of circulating microRNAs (c-miRNAs) to stratify patients based on their responsiveness to AA. We conducted an analysis of plasma samples obtained from a cohort of 33 mCRPC patients before and after three, six, and nine months of AA treatment. Using miRNA RT-qPCR panels for candidate discovery and TaqMan RT-qPCR for validation, we identified promising miRNA signatures. Our investigation indicated that a signature based on miR-103a-3p and miR-378a-5p effectively discriminates between non-responder and responder patients, while also following the drug's efficacy over time. Additionally, through in silico analysis, we identified target genes and transcription factors of the two miRNAs, including PTEN and HOXB13, which are known to play roles in AA resistance in mCRPC. In summary, our study highlights two c-miRNAs as potential companion diagnostics of AA in mCRPC patients, offering novel insights for informed decision-making in the treatment of mCRPC.

Background: Outcomes of castration-sensitive prostate cancer (CSPC) have improved owing to new therapies and early treatment, previously reserved for castration-resistant disease (CRPC). Prostatic-specific antigen (PSA) remains the most used marker to follow-up patients under treatment, but only limited data are available about the prognostic role of its changes over time and the impact of response to subsequent therapies. This analysis aims to assess the prognostic role of the magnitude and velocity of PSA response in CSPC and describe how this may affect the outcome to subsequent treatment outcomes in CRPC., Patients and Methods: A retrospective analysis was performed on patients with de novo CSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. PSA response (PSA50), defined as a decrease > 50% compared to baseline, PSA velocity (PSAv), defined as any decrease in PSA levels over time and the deep and fast PSA response (4mPSA50), defined as the PSA response reached within the threshold of 4 months from the beginning of androgen deprivation therapy (ADT) have been evaluated for their impact on survival. Survivals were estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional-hazard models, stratified according to baseline characteristics, were used to estimate hazard ratios for overall survival (OS)., Results: A totals of 94.4% of patients had PSA50, which was correlated to longer OS compared to patients without PSA50 (56.0 vs. 14.8 months; p<0.001). The median PSAv was 6.9 (ng/dl)/month, which was predictive for longer OS: Each decrease of 1 (ng/dl)/month was able to improve OS by 0.2% (HR=0.998, 95%CI=0.997-1.000; p=0.008). A total of 47.9% of patients reached 4mPSA50, with a median OS and progression-free survival (PFS) to ADT-based therapy of 101.0 and 23.4 months compared to 41.9 and 11.0 months for those who did not (p<0.001), respectively. The independent prognostic role of 4mPSA50 was retained even when evaluated in multivariable analysis adjusted for other baseline characteristics and early docetaxel for CSPC. In CRPC, 4mPSA50 evaluated during CSPC retains its prognostic role even if it does not predict a different outcome between patients treated with abiraterone/enzalutamide or taxanes., Conclusion: Achieving a deep and fast PSA response correlates with a better outcome in patients with de novo mCSPC, also positively influencing the prognosis of the subsequent first-line therapy for CRPC disease., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Real-world data suggest a possible interplay between androgen deprivation therapy (ADT) and susceptibility to and the severity of SARS-CoV-2 infection. As ADT is the backbone of prostate cancer treatment, various authors have evaluated different patient cohorts but the evidence provided is conflicting. The aim of this review is to assess the available publications concerning the role of ADT in preventing or reducing the severity of SARS-CoV-2 infection. After a literature search we identified four full papers, five letters, and four meeting abstracts, but these used different search methods and the quality of the evidence varied. They frequently had different endpoints, did not report the status of the prostate cancer patients and evaluated heterogeneous populations. The available data do not support the view that ADT protects against SARS-CoV-2 infection. Larger and more precise studies are warranted, considering variables that affect infection outcomes as these significantly influence the reliability of the findings., (Copyright © 2021. Published by Elsevier B.V.)

Background: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC)., Methods: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m 2 , oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration., Results: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%)., Conclusions: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit., Trial Registration Numbers: EudraCT 2014-000175-43 - NCT02453009., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Orazio Caffo is an advisor to Janssen, MSD and Bayer, and a speaker for Astellas, AstraZeneca, Bayer, Janssen, MSD, Pfizer and Sanofi. Cinzia Ortega is an advisor to Janssen, Astellas, Pfizer, Novartis and MSD, and a speaker for MSD, BMS and Sanofi. Donatello Gasparro is a speaker for and an advisor to Sanofi and Astellas. Vittorina Zagonel is an advisor to Bristol-Myers Squibb, MSD, Eisai and Italfarmaco, and a speaker for Roche, Bristol-Myers Squibb, Astellas Pharma, Servier, AstraZeneca, MSD, Janssen and Ipsen. Roberto Iacovelli is an advisor to Pfizer, Ipsen, Janssen, Astellas, MSD and BMS. Ugo De Giorgi is a consultant of Astellas Pharma, Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche and Sanofi. Elena Verri is an advisor to Astellas, Bayer, Janssen and Sanofi. Sebastiano Buti is a speaker for and advisor to BMS, Pfizer, Pierre-Fabre, MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis. Marco Maruzzo is an advisor to Pfizer, BMS, Janssen, MSD, Merck Serono and Ipsen. Giovanni Pappagallo is a counsellor and trainer for Astellas, AstraZeneca, Daiichi-Sankyo, Ipsen, Janssen, MSD, Pierre Fabre, Pfizer, Roche, Servier and Teva. Massimo Aglietta is an advisor to Bayer, BMS, Merck and Novartis, and has received travel support from BMS, Merck and Tesaro. Maurizio Nicodemo is a speaker for and an advisor to Bristol-Myers Squibb, Ipsen, Molteni and Janssen. Roberto Sabbatini is an advisor to Janssen, and a speaker for Astellas, Janssen and Sanofi. Franco Morelli is a speaker for MSD and Pfizer. Francesco Carrozza is a speaker for Janssen. Camillo Porta is a consultant of and speaker for Angelini, AstraZeneca, Bristol-Myers Squibb, Eisai, EUSA, General Electric, Ipsen, Merck, MSD, Novartis and Pfizer; an expert witness for EUSA and Pfizer; a member of the Protocol Steering Committee of Bristol-Myers Squibb, Eisai and EUSA and has received travel support from Roche. The remaining authors have no conflict of interest to be declared, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction : Recently, there has been a paradigm shift in the treatment of advanced prostate cancer (PCa) because the approval of a number of new agents has significantly improved overall survival. However, as PCa is a heterogeneous disease that may be more or less aggressive and patients may be more or less responsive to treatment, it is often debated whether or not it is acceptable to avoid active therapies. Areas covered : This review discusses different settings of advanced PCa. Expert opinion : In metastatic castration-resistant PCa, it is unethical not to use active treatments but the use of both androgen receptor targeting agents (ARTA) in sequence should be avoided in most patients and the use of the available agents for fourth-line treatment or beyond should only be considered for highly selected patients. In metastatic hormone-sensitive PCa, patients with de novo disease should receive one additional agent in combination with androgen deprivation therapy (ADT), whereas patients in relapse should be managed with ADT alone. In non-metastatic castration-resistant prostate cancer (PCa), all patients with a PSA doubling time of ≤6 months should receive one ARTA, whereas the others might wait until there is an acceleration in the kinetics of their PSA levels.

Background: Cancer-related pain, usually associated with bone metastases, is a frequent and debilitating morbidity in patients with prostate cancer. To date there are only limited data regarding the prognostic role of pain in men with metastatic castration-sensitive prostate cancer (mCSPC). The objective of our analysis was to assess if the presence of pain can be considered an independent prognostic factor in mCSPC patients., Methods: A retrospective analysis was performed on patients with mCSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. Patients were considered to have pain if this was reported within the patient's file or in case of a chronic analgesic therapy was found among the concomitant medications. Survivals were estimated by the Kaplan-Meier method, and compared across groups using the log-rank test. Cox proportional hazard models, stratified according to the baseline characteristics, were used to estimate hazard ratios for overall survival (OS). All the variables were significant if p < 0.05., Results: Data about pain were available for 365 cases and pain was present in 34.8% of patients. Pain was mainly associated with high value of prostate-specific antigen, metastatic bone extension regardless of the site, and lymph node involvement. mCSPC patients with pain had in most of the cases high-volume or Hr disease, and significant shorter OS (27.0 vs. 58.2 months, p < 0.001) and PFS (10.1 vs. 17.4 months, p < 0.001) compared to those without pain. The negative impact of pain on OS remained significant even if adjusted for CHAARTED or LATITUDE classification, and other significant baseline prognostic factors., Conclusions: This analysis supports the poor prognostic role of cancer-related pain in the setting of mCSPC patients. A prospective validation is required.

Background: Patients with cancer are at increased risk of complicated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but it is still unclear if the risk of mortality is influenced by cancer type or ongoing anti-cancer treatments. An interesting debate concerning the potential relationship between androgen deprivation therapy (ADT) and SARS-CoV-2 infection has recently been opened in the case of prostate cancer (PC), and the aim of this multi-centre cohort study was to investigate the incidence and outcomes of SARS-CoV-2 infection in patients with metastatic castration-resistant prostrate cancer (mCRPC)., Patients and Methods: We retrospectively reviewed the clinical records of patients with mCRPC who developed SARS-CoV-2 infection, and recorded their baseline clinical characteristics, their history of PC and SARS-CoV-2 infection, and their oncological status and treatment at the time of infection. The primary study end point was the death rate and the possible impact of the patients' PC-related history and treatments on mortality., Results: Thirty-four of the 1433 patients with mCRPC attending the participating centres (2.3%) developed SARS-CoV-2 infection, 22 (64.7%) of whom were hospitalised. Most of the patients were symptomatic, the most frequent symptoms being fever (70.6%), dyspnoea (61.8%), cough (52.9%) and fatigue (38.2%). After a median follow-up of 21 days (interquartile range: 13-41), 13 patients had died (38.2%), 17 recovered (50.0%) and four (11.7%) were still infected. The number of treatments previously administered for mCRPC had a significant impact on mortality (p = 0.004)., Conclusions: Our findings contribute additional data to the current debate concerning the postulated protective role of ADT, which seems to be less in patients with metastatic PC., Competing Interests: Conflict of interest statement O. C. reports receiving honoraria as speaker or advisor for Astra Zeneca, Astellas, Janssen and Pfizer. The other authors have no conflicts of interest to be declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63-75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status ( p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03-2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05-2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients.

Objectives: stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients., Methods: all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion., Results: 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (<14 mm). SBRT was safe and the 1-year local disease control was 87.7%. After SBRT, 18 patients (37.5%) permanently interrupted systemic therapy., Conclusions: consistently with the previous literature, our findings support the use of SBRT in selected mRCC patients., Competing Interests: Declaration of Competing Interest M. Bersanelli received research funding from Seqirus, Pfizer, Bristol-Myers Squibb (BMS) and Novartis and honoraria for advisory role and as speaker at scientific events from BMS, Novartis, Pierre-Fabre and Pfizer. S. Buti received research funding from Novartis and honoraria for advisory role and as speaker at scientific events from Pfizer, BMS, IPSEN, Pierre-Fabre, Merck Sharp & Dohme (MSD), AstraZeneca. G. Procopio received honoraria for advisory role from Bayer, BMS, Ipsen, MSD, Novartis, Pfizer. All other authors declared no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Over the last 10 years, a number of new agents approved for the treatment of metastatic castration-resistant prostate cancer have led to a significant improvement in overall survival. The addition of new agents to androgen deprivation therapy has also allowed a paradigmatic change in the treatment of metastatic hormone-sensitive prostate cancer by improving overall survival in comparison with androgen deprivation therapy alone. Furthermore, recent data concerning the efficacy of three different androgen receptor-targeting agents in patients with nonmetastatic castration-resistant prostate cancer have opened up new scenarios for future patients' management. Defining the best sequencing strategies for men with prostate cancer is a currently unmet medical need, and choosing treatment is often challenging for clinicians because of the lack of direct comparisons of the available agents. The aim of this paper is to provide a comprehensive review of the literature concerning current sequencing strategies for prostate cancer patients.

Aim: To evaluate activity of metronomic cyclophosphamide (mCTX) in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) patients., Patients & Methods: We retrospectively evaluated a consecutive series of 74 mCRPC patients treated with at least one new agent after docetaxel failure, who received once-daily oral mCTX treatment at a fixed dose of 50 mg., Results: The treatment was well tolerated. Sixteen percent of the patients experienced a major biochemical response. Median progression-free survival was 4.0 months, and median overall survival was 8.1 months., Conclusions: In the modern context of mCRPC, mCTX may represent a valuable and inexpensive alternative to new agents, which have shown similar activity in heavily pretreated patients.

In few years the scenario of metastatic prostate carcinoma treatment has radically changed due to improved knowledge of those mechanisms responsible of prostatic cancer cells survival and proliferation. Five new therapeutic agents (abiraterone acetate, enzalutamide, cabazitaxel, radium-223, sipuleucel-T), all able to improve overall survival, have been introduced in the management of metastatic castration-resistant prostate cancer. Moreover, recent evidences showed that adding docetaxel chemotherapy or abiraterone acetate to androgen deprivation therapy significantly increases overall survival of de novo castration-sensitive metastatic prostate cancer patients. Due to this rapid therapeutic evolution clinicians face one crucial challenge: the choice of the best treatment sequencing. In particular, there are no prospective data to guide clinical decision in patients with progressive disease after docetaxel or abiraterone acetate treatment for castration sensitive disease. In this review we provide an overview of the therapeutic agents available for both castration-sensitive and castration-resistant prostate cancer. We propose some biological and clinical insights helpful in selecting the most appropriate treatment for patients progressing after metastatic castration-sensitive prostate cancer treatment with docetaxel or abiraterone acetate., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting., Patients and Methods: We conducted a multicenter retrospective analysis in the Triveneto region of Italy., Results: One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia., Conclusion: This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To collect efficacy and safety data of enzalutamide after docetaxel, we retrospectively evaluated the Italian Named Patient Program results., Patients & Methods: Two hundred and nine metastatic castration-resistant prostate cancer patients were enrolled. Median age was 73 years. Total 42.1% patients had pain, 14.4% had a performance status of two and 59.8% had a Gleason score ≥8. Total 31.1% had previously received ≥2 chemotherapies, 15.3 and 12% had been previously treated with abiraterone and cabazitaxel, respectively and 14.8% had received both., Results:  Median progression-free survival and overall survival were 4.8 and 13.1 months, respectively. A prostate-specific antigen reduction ≥50% was observed in 49.1%. Total 32.7% abiraterone-pretreated patients achieved a biochemical response compared with 56% of abiraterone-naive patients., Conclusion:  Enzalutamide was safe and well tolerated. Its antitumor activity in abiraterone-pretreated patients was limited.

Patients who are carriers of inherited mutations in essential component of DNA repair pathways have a significantly higher lifetime risk for developing cancer compared to the population of reference. Recent advances in DNA next-generation sequencing technology have allowed screening for carriers of those mutations, allowing development of promising risk-reduction strategies and providing the rationale to personalize the therapeutic approach for these patients. New intriguing scenarios are opening nowadays for the management of prostate cancer in patients with germline or somatic mutations in components of DNA repair pathways (e.g., BRCA1 and BRCA2 genes), such as specific screening policies and new therapeutic strategies involving PARP inhibitors or platinum-based chemotherapy.

Androgen receptor is the major driver of and testosterone the natural growth factor of prostate cancer (PC). Studies exploring the relationship among circulating testosterone levels, PC aggressiveness, and patient prognosis showed contradictory results. We performed a comprehensive literature search for studies reporting the independent relationship between serum testosterone and prognosis of PC patients. Meta-analyses using random effects models were conducted to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 25 articles that evaluated the prognostic value of testosterone in early-stage PC (8 studies), in advanced PC either before (4 studies) or during androgen deprivation therapy (ADT) (5 studies), and in castration-resistant PC (8 studies). In early PC, serum testosterone level was not prognostic in terms of overall survival (HR = 1.03; 95% CI, 0.99-1.08; P = .19) and biochemical recurrence (HR = 0.99; 95% CI, 0.87-1.13; P = .93). In advanced PC, higher testosterone levels before ADT were associated with a reduced risk of death (HR = 0.58; 95% CI, 0.45-0.74; P < .0001). During ADT, lower levels were associated with a reduced risk of death (HR = 0.48; 95% CI, 0.28-0.81; P = .006) and progression (HR = 0.59; 95% CI, 0.46-0.77; P < .0001). In castration-resistant PC patients, higher testosterone levels predicted a reduced risk of progression (HR = 0.33; 95% CI, 0.11-0.97; P = .04) but not of death (HR = 0.86; 95% CI, 0.69-1.07; P = .18). The heterogeneity of the included studies is a major limitation of this meta-analysis. The relationship between circulating testosterone and PC prognosis varies in different clinical settings and according to ADT administration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Metabolic syndrome (MS) and inflammation (INF) alterations are among the factors involved in cancer progression. The study aimed to assess the relationship between MS and INF and its effect on progression-free/overall survival (PFS/OS) in metastatic castration-resistant prostate cancer (mCRPC) treaed with abiraterone or enzalutamide., Methods: We, retrospectively, evaluated patients with mCRPC in 7 Italian Institutes between March 2011 and October 2016. MS was defined by modified adult treatment panel-III criteria. INF was characterized by at least one of these criteria: neutrophil to lymphocyte ratio ≥ 3, elevated erythrocyte sedimentation rate or C-reactive protein., Results: Eighty-three of 551 (15.1%) patients met MS criteria at baseline and 34 (6.2%) during treatment. MS patients (MS+) presented a greater INF profile compared to MS- (P<0.0001). Median PFS was 3.7 for MS+ vs. 8.7 months for MS- (hazard ratio [HR] = 2.77; 95% CI: 2.12-3.61; P<0.0001). Median OS was 6.9 and 19 months in MS+ and MS-, respectively (HR = 3.43; 95% CI: 2.56-4.58; P<0.0001). We also demonstrated INF led to shorter PFS and OS (4.5 vs. 8.5 months, HR = 1.48, 95% CI: 1.15-1.90, P = 0.002, and 11.2 vs. 18.8 months, HR =1.66, 95% CI: 1.26-2.18, P = 0.0003, respectively). The combination of MS with INF provided the identification of high-risk prognostic group (MS+/INF+ vs. MS-/INF-) with worse PFS (3.7 vs. 9 months, HR = 2.7, 95% CI: 1.88-3.89, P<0.0001) and OS (6.3 vs. 20.4 months, HR = 4.04, 95% CI: 2.75-5.93, P<0.0001). Multivariable analysis confirmed that MS was independently associated with PFS (HR = 2.07; 95% CI: 1.03-4.18; P = 0.041) and OS (HR = 4.87; 95% CI: 2.36-10.03; P<0.0001). The absence of INF as an independent predictor of survival underlined the correlation between MS/INF., Conclusions: Pretreatment identification of MS and INF alterations might represent an available and easy tool for better prognostication of patients with mCRPC. A prospective evaluation is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Abiraterone acetate, which targets enzymatic complexes playing a central role in steroidogenesis, demonstrated to increase survival significantly in both chemo-naive and docetaxel pretreated, becoming one of the drugs of choice for metastatic castration-resistant prostate cancer. More recently, this agent in combination to androgen deprivation therapy demonstrated to be efficacious also in metastatic castration-sensitive prostate cancer. The present review is aimed to outline the clinical development of abiraterone acetate, the pivotal trials which led to its approval for the clinical practice, new evidence about its efficacy in metastatic castration-sensitive prostate cancer, its place in the therapeutic landscape of prostate cancer and future directions of development.

Introduction: Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients., Patients and Methods: Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed. Response rate, progression-free survival (PFS), and overall survival (OS) were evaluated. Univariate and descriptive analyses were performed., Results: Thirty-seven patients with nccRCC were treated with first-line pazopanib; 51% had papillary histology, 24% chromophobe, 22% unclassified, and 3% had Xp11.2 translocation. Dose reductions/temporary interruptions for toxicity were required in 46% of cases. Grade (G) 3/4 toxicity was seen in 32%, G1/2 in 89% of cases; 81% achieved disease control, with 10 partial responses (27%) and 20 cases of stable disease (54%); 16% of patients had disease progression as best response. Median PFS and OS were 15.9 and 17.3 months, respectively. In univariate analysis, nephrectomy (P = .020), Memorial Sloan Kettering Cancer Center (MSKCC) score (P < .001), basal neutrophil/lymphocyte ratio (NLR; P = .009) and performance status (PS) (P = .001) were associated with PFS; MSKCC score (P < .001), International Metastatic Renal Cell Carcinoma Database Consortium score (P = .003), PS (P < .0001), nephrectomy (P = .002), histology (P = .035), dose reductions/interruptions (P = .039), best response to treatment (P < .001), and NLR (P = .008) were associated with OS., Conclusion: In nccRCC patients, treatment with pazopanib was effective and feasible; dose reductions required for toxicity were similar as expected in ccRCC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To assess the activity of weekly paclitaxel (wPCT) in pretreated patients with advanced non-small-cell lung cancer (aNSCLC). In 2005, we included wPCT 80 mg/m for 6 consecutive weeks, followed by a 2-week interval in our department's everyday clinical practice guidelines for the second-line (or subsequent) treatment of patients with nonsquamous histologies who have previously received pemetrexed-based treatments and patients with squamous histology. In the absence of clinical evidence of disease progression, patients repeat the pretreatment staging procedures after 16 weeks (two cycles) and, in the absence of disease progression or severe toxicity, continue treatment for a maximum of four courses. Between May 2005 and December 2013, we treated 60 patients (47 in second-line and 13 in third/fourth line), who received a median of two courses (range: 1-4). The most frequent toxicity was grade 1-2 neutropaenia (five patients); only four patients experienced grade 3-4 toxicity. When used as a second-line treatment, wPCT led to a disease control rate of 36.2%, with a median progression-free survival of 3.7 months and a median overall survival of 9.0 months; when used in the third/fourth line, the disease control rate was 41.7%, the median progression-free survival was 5.0 months and the median overall survival was 10.3 months. Our data confirm that wPCT is active and well tolerated in an unselected patient population with aNSCLC and can be considered a valuable alternative to docetaxel in a second-line treatment.

Background: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome., Patients and Methods: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses., Results: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge., Conclusion: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon., (© 2017 Wiley Periodicals, Inc.)

Introduction: Despite the growing number of oral agents available for cancer treatment, their efficacy may be reduced due to the lack of adherence, inappropriate adverse event self-management and arbitrary dose adjustment. The management of anticancer therapies could exponentially benefit from the introduction of mobile health technologies in a highly integrated electronic oncology system., Methods and Analysis: We plan to customise and fine-tune an existing monitoring TreC platform used in different chronic diseases in the oncology setting. This project follows a multistep approach with two major purposes: 1. participatory design techniques driven by Health Literacy and Patient Reported Outcomes principles in order to adapt the system to the oncology setting involving patients and healthcare providers; 2. a prospective training-validation, interventional, non-pharmacological, multicentre study on a series of consecutive patients with cancer (20 and 60 patients in the training and validation steps, respectively) in order to assess system capability, usability and acceptability. The novel Onco-TreC 2.0 is expected to contribute to improving the adherence and safety of cancer care, promoting patient empowerment and patient-doctor communication., Ethics and Dissemination: Ethical approval was obtained from the Independent Ethics Committees of the participating institutions (CEIIAV protocol Number 2549/2015; reference Number 1315-PU). Informed consent will be obtained from all study participants. Findings will be disseminated through peer-reviewed journals, conferences and event presentations., Trial Registration Number: ClinicalTrials.gov (NCT02921724); (Pre-results). Other study ID Number: IRST100.18., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The treatment of elderly patients with cancer is usually viewed by clinicians as a challenge, because of the age-related decline in normal organ function and the frequent concomitant administration of multiple drugs for comorbid conditions. Clinicians therefore tend not to prescribe antineoplastic agents (mainly in the case of chemotherapy) to elderly patients, with the fear of excess toxicity leading to an unfavorable cost:benefit ratio. The cutoff age defining a cancer patient as elderly is usually 70 years, but over the last 10 years clinicians have paid more attention to functional status, as evaluated by means of a comprehensive geriatric assessment and comorbidity burden, rather than chronological age. In the case of metastatic castration-resistant prostate cancer (mCRPC), depending on their age at the time of diagnosis of PC, many (if not most) of the patients are more than 70 years old, and a fair number are very elderly patients aged ≥80 years. The availability of various agents capable of significantly prolonging survival has dramatically changed the therapeutic landscape of mCRPC patients, but very elderly patients are usually underrepresented in pivotal trials. This narrative review considers the available data concerning elderly and very elderly mCRPC patients enrolled in pivotal trials and the information provided by reports of everyday clinical practice, in order to explore the challenges related to the clinical management of this special population., Competing Interests: The authors report no conflicts of interest in this work.

Background: A systemic immune-inflammation index (SII) based on neutrophil ( N ), lymphocyte ( L ), and platelet ( P ) counts has shown a prognostic impact in several solid tumors. The aim of this study is to evaluate the prognostic role of SII in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone post docetaxel. Patients and Methods: We retrospectively reviewed consecutive mCRPC patients treated with abiraterone after docetaxel in our Institutions. X-tile 3.6.1 software, cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR) defined as N/L and platelets-to-lymphocyte ratio (PLR) as P/L. Overall survival (OS) and their 95% Confidence Intervals (95% CI) was estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of SII, PLR, and NLR on overall survival (OS) was evaluated by Cox regression analyses and on prostate-specific antigen (PSA) response rates were evaluated by binary logistic regression. Results: A total of 230 mCRPC patients treated abiraterone were included. SII ≥ 535, NLR ≥ 3 and PLR ≥ 210 were considered as elevated levels (high risk groups. The median OS was 17.3 months, 21.8 months in SII < 535 group and 14.7 months in SII ≥ 535 ( p < 0.0001). At univariate analysis Eastern Cooperative Oncology Group (ECOG) performance status, previous enzalutamide, visceral metastases, SII, NLR, and PLR predicted OS. In multivariate analysis, ECOG performance status, previous enzalutamide, visceral metastases, SII, and NLR remained significant predictors of OS [hazard ratio (HR) = 5.08, p < 0.0001; HR = 2.12, p = 0.009, HR = 1.77, 95% p = 0.012; HR = 1.80, p = 0.002; and HR = 1.90, p = 0.001, respectively], whereas, PLR showed a borderline ability only (HR = 1.41, p = 0.068). Conclusion: SII and NLR might represent an early and easy prognostic marker in mCRPC patients treated with abiraterone. Further studies are needed to better define their impact and role in these patients.

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8-90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7-4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5-9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5-14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2-20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07-1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10-1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients.

Objective: Prostate-specific antigen (PSA) decline by 50 % from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the association between PSA changes at 4 weeks and clinical outcome., Patients and Methods: Eligible patients had PSA levels assessed at baseline, and monthly during enzalutamide treatment. Early PSA increase was defined as an increased PSA level at 4 weeks ≥20 % (PSA + 20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥30 % (PSA30w4) and ≥50 % (PSA50w4) from baseline. Progression-free survival (PFS), overall survival (OS) and their 95 % confidence intervals (CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. The impact of early PSA increase and decline on PFS and OS was evaluated by Cox regression analyses., Results: We assessed 193 patients with median age of 73 years (range 43-91 years). The median follow-up was 11.7 months (range 0.5-27.4 months). PSA + 20w4 predicted both PFS and OS [HR 6.50 (95 % CI 2.63-16.07; p < 0.0001) and HR 10.54 (95 % CI 4.02-27.64; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95 % CI 0.21-0.67; p = 0.0009) and HR 0.34 (95 % CI 0.19-0.60; p = 0.0003), respectively]., Conclusions: An early PSA increase, defined as a PSA level at 4 weeks ≥20 % (PSA + 20w4), could be useful to quickly identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA + 20W4 as an early biomarker of primary resistance to enzalutamide.

Background: Abiraterone acetate (AA), a selective inhibitor of the CYP17 enzyme, demonstrated a significant improvement in the treatment of patients with metastatic castration-resistant prostate cancer. The risk of endocrine side effects, mainly an increased adrenal mineralocorticoid production, could limit its use in patients with atrial fibrillation., Methods: We retrospectively reviewed the clinical records of 85 metastatic castration-resistant prostate cancer patients treated with AA at our institutions and identified six patients suffering from concomitant atrial fibrillation., Results: In these six patients, the median duration of AA treatment was 11.5 months (range 4-22 months) with a biochemical response in three patients. No significant cardiac events were observed during the treatment., Conclusion: Our data suggest that AA may be safely administered in patients with atrial fibrillation.

Over the last ten years, two new-generation hormonal drugs and two chemotherapeutic agents have been approved for the treatment of metastatic castration-resistant prostate cancer. Unfortunately, some patients have primary resistance to them and the others eventually develop secondary resistance. It has recently been suggested that the presence of androgen receptor splice variants plays a leading role in the primary and secondary resistance to the new hormonal drugs, whereas their presence seem to have only a partial effect on the activity of the chemotherapeutic agents. The aim of this paper is to review the published data concerning the role of androgen receptor splice variants in prostate cancer biology, and their potential use as biomarkers when making therapeutic decisions.

Background: Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting., Patients and Methods: We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics., Results: We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days., Conclusion: A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

Aim: High rate of non-target lesions in metastatic castration-resistant prostate cancer usually limits applicability of Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and this has led to a growing interest in using PET/computed tomography (CT). We prospectively investigated the role of (18)F-choline (FCH)-PET/CT in patients receiving enzalutamide after docetaxel., Patients & Methods: 30 patients were monitored by means of FCH-PET/CT before and during the treatment. A Cox proportional hazards regression model was used to assess the associations between metabolic parameters and clinical outcomes., Results: Univariate analysis showed no significant correlation between biochemical and FCH-PET responses. Multivariate analysis showed that only baseline maximum standardized uptake value (SUVmax) significantly correlated with biochemical progression-free survival, radiological progression-free survival and overall survival., Conclusion: Our findings suggest that FCH-PET/CT may play a role in defining prognosis of patients receiving enzalutamide because baseline SUVmax proved to be an independent prognostic factor.

We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer., Patients & Methods: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes., Results: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival., Conclusion: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.

Unlabelled: Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population., Background: Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population., Patients and Methods: We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression-free survival (PFS). Safety and clinical outcomes were also analyzed by age group (< 80 and > 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables., Results: In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature., Conclusion: Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer.

Background: Two new hormonal agents (NHAs), abiraterone and enzalutamide, and one chemotherapeutic agent, cabazitaxel (CABA) improved overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progress after docetaxel. Although several analyses of patient cohorts receiving a sequence of two different new agents (NAs) after docetaxel have been published, no definite conclusions can be drawn regarding the best treatment strategy., Materials and Methods: All published studies reporting monthly OS rates of mCRPC patients receiving third-line NA after having previously received docetaxel and another NA have been analyzed. The treatments were merged into three groups: one NHA followed by another, one NHA followed by CABA, and CABA followed by one NHA. The cumulative monthly OS rates in each group were determined using a weighted-average approach., Results: Thirteen retrospective studies including 1016 patients who received NHA/NHA (469), NHA/CABA (318) or CABA/NHA (229) were evaluated. The 12-month OS rates were 28.5%, 61.3%, and 76.4%, respectively. There were no statistically significant differences in terms of known prognostic factors., Conclusions: Although the retrospective nature of the studies and potential selection biases, our data seem to confirm the potential cumulative survival benefit of using the NAs sequentially after docetaxel. There was no clear superiority of any one of the three strategies, but a sequence that includes CABA seems to suggest a possible OS advantage., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Metabolic syndrome (MS) has not yet been studied in castration-resistant prostate cancer (CRPC) men treated with novel hormonal therapies. The study aims to assess the impact of MS on outcome from time starting abiraterone., Patients and Methods: We retrospectively evaluated a consecutive series of metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the time of initiation of abiraterone, during treatment and follow-up., Results: Sixty-seven of 178 patients evaluated (37.6%) met MS criteria at baseline, before abiraterone initiation, whereas for 11 (9.9%) without MS before treatment with abiraterone this occurred during treatment. Median PFS was equal to 4.7 months for patients with MS versus 9 months for those without MS. Patients with MS had an increased risk of 71% of progression or death for all causes than patients without MS (HR = 1.7, 95% CI [1.2-2.4], P = 0.03). Median OS was 14.7 months and 22.3 months in patients with and without MS, respectively. After adjusting for covariates, MS resulted not significantly associated to OS (HR = 1.42, 95% CI [0.91-2.22], P = 0.073)., Conclusions: The presence of MS is a significant risk factor for shorter PFS in CRPC patients treated with abiraterone, even if it does not show a significant impact on OS. A prospective evaluation is warranted., (© 2015 Wiley Periodicals, Inc.)

Background: The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit., Objective: To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA., Design, Setting, and Participants: We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel., Outcome Measurements and Statistical Analysis: The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis., Results and Limitations: We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences., Conclusions: We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy., Patient Summary: It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT)., Materials and Methods: We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient., Results: QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy., Conclusions: The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced.

Background: The prognosis of younger patients with prostate cancer is unclear, and the very few studies assessing those with metastatic castration-resistant prostate cancer (mCRPC) have mainly involved patients treated with older therapies. The aim of this observational study was to evaluate the clinical outcomes of a contemporary series of docetaxel-treated patients with mCRPC who were 60 years and younger., Patients and Methods: We retrospectively identified 134 patients who were 60 years and younger who were treated with docetaxel in 25 Italian hospitals and recorded their predocetaxel history of prostate cancer, their characteristics at the start of chemotherapy, and their postdocetaxel treatment history and outcomes., Results: Most of the 134 consecutive patients with mCRPC received the standard 3-week docetaxel schedule; median progression-free survival (PFS) was 7 months, and 90 patients underwent further therapies after progression. The median overall survival (OS) from the start of docetaxel treatment was 21 months, but OS was significantly prolonged by the postprogression treatments, particularly those based on the new agents such as cabazitaxel, abiraterone acetate, or enzalutamide. OS was significantly shorter in the patients with a shorter interval between the diagnosis of prostate cancer and the start of docetaxel treatment; those who received hormonal treatment for a shorter period; those with shorter prostate-specific antigen doubling times; and those with lower hemoglobin levels, a worse performance status, and higher lactate dehydrogenase levels before starting treatment with docetaxel., Conclusions: The findings of this first study of clinical outcomes in a contemporary series of younger patients with mCRPC showed that their survival is similar to that expected in unselected patients with mCRPC who were of any age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The potential benefits of the introduction of electronic and mobile health (mHealth) information technologies, to support the safe delivery of intravenous chemotherapy or oral anticancer therapies, could be exponential in the context of a highly integrated computerized system., Objective: Here we describe a safe therapy mobile (STM) system for the safe delivery of intravenous chemotherapy, and a home monitoring system for monitoring and managing toxicity and improving adherence in patients receiving oral anticancer therapies at home., Methods: The STM system is fully integrated with the electronic oncological patient record. After the prescription of chemotherapy, specific barcodes are automatically associated with the patient and each drug, and a bedside barcode reader checks the patient, nurse, infusion bag, and drug sequence in order to trace the entire administration process, which is then entered in the patient's record. The usability and acceptability of the system was investigated by means of a modified questionnaire administered to nurses. The home monitoring system consists of a mobile phone or tablet diary app, which allows patients to record their state of health, the medications taken, their side effects, and a Web dashboard that allows health professionals to check the patient data and monitor toxicity and treatment adherence. A built-in rule-based alarm module notifies health care professionals of critical conditions. Initially developed for chronic patients, the system has been subsequently customized in order to monitor home treatments with capecitabine or sunitinib in cancer patients (Onco-TreC)., Results: The STM system never failed to match the patient/nurse/drug sequence association correctly, and proved to be accurate and reliable in tracing and recording the entire administration process. The questionnaires revealed that the users were generally satisfied and had a positive perception of the system's usefulness and ease of use, and the quality of their working lives. The pilot studies with the home monitoring system with 43 chronic patients have shown that the approach is reliable and useful for clinicians and patients, but it is also necessary to pay attention to the expectations that mHealth solutions may raise in users. The Onco-TreC version has been successfully laboratory tested, and is now ready for validation., Conclusions: The STM and Onco-TreC systems are fully integrated with our complex and composite information system, which guarantees privacy, security, interoperability, and real-time communications between patients and health professionals. They need to be validated in order to confirm their positive contribution to the safer administration of anticancer drugs.

Objective: To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP)., Patients and Methods: We retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals., Results: We assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3-4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression-free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases., Conclusions: Our data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post-docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest., (© 2014 The Authors. BJU International © 2014 BJU International.)