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Introduction: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is the most important prognostic score to stratify patients with metastatic renal cell carcinoma (mRCC), helping to guide treatment choice in first line. We hypothesized that IMDC change may also exert a prognostic role in subsequent lines of mRCC therapy., Methods: Meet-URO 15 is a multicenter Italian study of patients with mRCC receiving nivolumab as a second or subsequent line of therapy. This posthoc analysis aimed to evaluate the overall survival (OS) and progression-free survival (PFS) from nivolumab start as primary endpoints, overall response rate (ORR) and disease-control rate (DCR) as secondary endpoints, according to the change in the IMDC category from the first-line setting (baseline) to nivolumab start. Patients with available prognostic IMDC category information at baseline and before nivolumab were included., Results: 492 patients were included in the analysis. At baseline, 165 (33.5%), 287 (58.3%), and 40 patients (8.2%) had favorable, intermediate, and poor IMDC categories, respectively. Before nivolumab, 364 patients (73.9%) remained in the same prognostic category as at baseline, 27 (5.5%) improved, and 101 (20.5%) deteriorated. Significantly longer mPFS (P = .01) and mOS (P < .01) were reached by patients with a stable favorable group compared to those worsening to intermediate/poor. A longer mOS was also achieved from intermediate/poor patients who improved their IMDC category before nivolumab compared to those remaining stable/worsening (P < .01 and P = .04, respectively). Maintaining IMDC category stability from baseline to nivolumab determined a more consistent DCR in favorable patients (P = .03). Overall, patients who improved their IMDC risk score reached better survival outcomes than those who remained stable/deteriorated., Conclusions: In our sub-analysis, the shift in the IMDC risk category appears to be a helpful prognostic tool for assessing the outcomes of patients with mRCC treated with ≥2nd line nivolumab., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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: Immune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy., Materials and Methods: This retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed., Results: Among 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels <140 mE/L (18.7 vs. 12.0, p=0.04). Post-treatment sodium levels ≥140 mEq/L were associated with improved PFS (9.6 vs . 3.2 months) and OS (25.1 vs. 8.8 months) (p=0.05 and p<0.01, respectively). Patients with consistent sodium levels ≥140 mEq/L at both time points exhibited the best outcomes compared to those with lower values (PFS 11.5 vs. 3.3 months and OS 42.2 vs. 9.0 months, respectively, p<0.01). Disease control rate was significantly higher in the latter group (p<0.01). Multivariate analysis confirmed the prognostic significance of sodium levels., Conclusion: Elevated sodium levels (≥140 mEq/L) pre- and post-ICI treatment correlate with better survival outcomes in mRCC patients with BMs. This finding suggests sodium level assessment as a potential prognostic factor in these patients and warrants further investigation, particularly in combination immunotherapy settings., Competing Interests: GB: Speaker bureau: Astellas, Astrazeneca, Amgen. Patents: n. 4 patents with ST Microelectronics. Travel, Accommodations for scientific conferences: Merck, Janssen. UG: services as advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS BMS, IPSEN, Janssen, Pfizer. LC: has received honoraria for advisory boards, speaker engagements and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, A.A.A.; past MSD employee in Medical Affairs. MS: honoraria as consultant or advisory role from Janssen; grant for participation at scientific events: Astellas Pharma, Sanofi, Roche Novartis, Ipsen, Janssen, Bristol Myers Squibb, Pfizer; research funding: Roche, Merck, Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Catalano, Rebuzzi, Maruzzo, De Giorgi, Buti, Galli, Fornarini, Zucali, Claps, Chiellino, Zampiva, Pipitone, Ricotta, Sorarù, Mollica, Tudini, Fratino, Prati, Caffo, Atzori, Morelli, Prati, Nolè, Vignani, Cavo, Di Napoli, Malgeri, Naglieri, Signori, Banna, Rescigno, Cerbone, Antonuzzo and Roviello.)

Background: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment., Materials and Methods: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses., Results: A total of 571 patients with a median age of 61 years (range 17-85) were included in the analysis. With a median follow-up of 22.1 (1.0-89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders., Conclusion: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy., (© 2024. The Author(s).)

Introduction: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors., Patients and Methods: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy., Results: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83)., Conclusion: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes., Competing Interests: Disclosure The other authors declare no conflict of interest. Francesco Pierantoni: Advisory board: Eli Lilly; Speaker and travel fees: Pfizer, BMS, MSD, AstraZeneca, Jannsen, Takeda, Merck, Astellas, Ipsen. Paola Ermacora: MSD, BMS, AAA, Astellas, Recordati, Eisai (advisory board), Jansenn (travel grant)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare physical therapy (PT) utilization, timing of return-to-sport (RTS) test and hop test performance by age and between sexes in youth after anterior cruciate ligament reconstruction (ACLR)., Design: Multicenter retrospective cohort., Methods: A retrospective review of adolescents after primary ACLR was conducted. Participants completed return-to-sport (RTS) tests including single-legged hop testing. PT frequency, average weekly visits, and timing of RTS test were calculated. T-tests assessed the effect of age and sex on average weekly PT visits and multivariable logistic regressions assessed odds of passing hop tests., Results: 289 participants were included (15.7 ± 1.9 years). There was no difference in average weekly PT visits (p = 0.321) or time to RTS test (p = 0.162) by age. There were significant differences in average weekly PT visits (p = 0.047) and mean time from surgery to RTS test (p = 0.048) between sexes with small effect sizes (d = 0.24 and d = 0.21, respectively). Age and sex had no effect on odds of passing hop tests (OR, 1.29; 95% CI, 0.71-2.35 and OR, 0.79; 95%CI, 0.43-1.45, respectively)., Conclusion: In a youth cohort, age and sex may have no clinically important effect on PT visit utilization, timing of RTS test or hop test performance., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal., Methods: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS)., Results: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P < . 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS., Conclusion: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy., Competing Interests: Disclosure All authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Immunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy., Methods: The Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS., Results: Overall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 - 10.1), while mPFS was 7.0 months (95% CI: 5.7 - 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59)., Conclusion: We found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS., Competing Interests: Dr. SB received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, Astellas. Dr. SR received honoraria as speaker at scientific events and travel accommodation from BMS, Amgen, GSK, Ipsen, Astellas, Janssen, MSD. Dr. DB received honoraria as advisory role by Ipsen, Astellas, Janssen, Novartis, BMS, MSD, Pfizer, Merck and travel accommodation from Ipsen, Janssen, MSD, Merck. Dr. UD services as advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS BMS, IPSEN, Janssen, Pfizer. Dr. SC received honoraria as speaker at scientific events/advisory boards and travel accommodation from BMS, Ipsen, MSD, Pierre-Fabre, Bayer, Gentili. Dr. PZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme MSD, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, Astrazeneca, Roche and Bayer. Dr. GPro services advisory boards/consulting for Astellas, AstraZeneca, BMS, Janssen, IPSEN, Merk, MSD, Novartis, Pfizer. Dr. CB received honoraria from advisory board/clinical trials/conference speaking/travel grant with Astellas, AstraZeneca, Bayer, BMS, Clovis, Exelixis, GSK, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi. Dr. MSo services advisory boards/consulting for Janssen, received research funding from Janssen, Roche and Merck and received travel accomodation from Ipsen, BMS, Janssen, Pfizer, Novartis, Astellas, Sanofi, Roche. Dr. FM services advisory boards for Pfizer and MSD. Dr. PR services advisory boards for MSD, AstraZeneca and Janssen. Dr. GF services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, Merck and received travel accomodation from Astellas, Janssen, Bayer. Dr. GB reports personal fees from AstraZeneca and Astellas for speaker bureau. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Murianni, Signori, Buti, Rebuzzi, Bimbatti, De Giorgi, Chiellino, Galli, Zucali, Masini, Naglieri, Procopio, Milella, Fratino, Baldessari, Ricotta, Mollica, Sorarù, Tudini, Prati, Malgeri, Atzori, Di Napoli, Caffo, Spada, Morelli, Prati, Nolè, Vignani, Cavo, Lipari, Roviello, Catalano, Damassi, Cremante, Rescigno, Fornarini and Banna.)

Aim: To define the prognostic significance of first-line TKI in mRCC patients receiving nivolumab. Materials and methods: A total of 571 mRCC patients who received ≥second line nivolumab were included in this subanalysis. The correlation between prior TKI (sunitinib vs. pazopanib) and overall response rate (ORR), disease control rate, progression-free survival and overall survival were investigated. Additionally, the impact of TKI choice according to the International Metastatic RCC Database Consortium prognostic score was examined. Results: There was no significant difference between sunitinib and pazopanib groups in terms of mPFS, mOS, overall response rate and disease control rate. Moreover, no difference between sunitinib and pazopanib was found according to the International Metastatic RCC Database Consortium prognostic score. Conclusion: There is no conclusive evidence favoring pazopanib or sunitinib treatment before initiating nivolumab therapy in metastatic renal cell carcinoma patients.

Importance: Low sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs)., Objective: To investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy., Design, Setting, and Participants: In this retrospective cohort study, the clinical and biochemical data of patients with mRCC receiving nivolumab were collected from October 2015 to November 2019 as part of a multicenter Italian study. Data analysis was performed from February to March 2023., Exposure: Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks and, since May 2018, at a fixed dose of 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were divided into 2 groups according to their median serum sodium value (<140 or ≥140 mEq/L)., Main Outcomes and Measures: The primary outcomes were the associations of pre-ICI and post-ICI sodium levels with overall survival (OS), progression-free survival (PFS), objective response rate, and disease control rate (DCR). The Kaplan-Meier method was used to estimate PFS and OS, and differences between groups were compared using the log-rank test., Results: A total of 401 patients with mRCC receiving nivolumab as second-line therapy were evaluated, and 355 eligible patients (median [range] age, 76 [44-84] years; 258 male patients [72.7%]) were included in the final cohort. Among patients with pre-ICI sodium greater than or equal to 140 mEq/L compared with those with sodium less than 140 mEq/L, the median PFS was 9.3 months (95% CI, 6.5-11.5 months) vs 7.4 months (95% CI, 4.6-10.1 months; P = .90), and the median OS was 29.2 months (95% CI, 21.8-35.9 months) vs 20.0 months (95% CI, 14.1-26.8 months; P = .03). Patients with post-ICI sodium values greater than or equal to 140 mEq/L had longer PFS (11.1 months [95% CI, 8.5-1.5 months] vs 5.1 months [95% CI, 4.1-7.5 months]; P = .01) and OS (32.9 months [95% CI, 25.1-42.6 months] vs 17.1 months [95% CI, 12.6-24.5 months]; P = .006) compared with patients with sodium values less than 140 mEq/L. Patients with both pre-ICI and post-ICI sodium values greater than or equal to 140 mEq/L exhibited a significant improvement in clinical outcomes compared with those with a value less than 140 mEq/L (PFS, 11.5 months [95% CI, 8.8-16.4 months] vs 5.8 months [95% CI, 4.4-8.3 months]; P = .008); OS, 37.6 months [95% CI, 29.0-49.9 months] vs 19.4 months [95% CI, 14.1-24.5 months]; P = .01). Moreover, sodium levels greater than or equal to 140 mEq/L were associated with significantly better DCR than lower sodium levels., Conclusions and Relevance: In this retrospective cohort study of patients with mRCC receiving nivolumab, sodium values greater than or equal to 140 mEq/L, both before and/or after ICI, were associated with better OS and PFS, as well as a higher DCR, compared with levels less than 140 mEq/L. These findings suggest that sodium levels may be associated with survival outcomes in patients with mRCC and may have potential use as variables to consider in patients' risk scores.

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20-25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7-11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.

Objective: Examine the effect of insurance type on physical therapy (PT) utilization and outcomes within pediatric and adolescent patients after anterior cruciate ligament reconstruction., Design: Multicenter retrospective cohort study., Methods: PT visits and functional hop test performance were extracted into a shared database. The average number of PT visits per week was assessed overall and by time period. Independent samples t-test examined the effect of insurance on PT utilization and the effect of insurance status on the odds of passing single-legged hop tests was assessed using multivariable logistic regression., Results: A total of 281 patients (15.7 ± 1.9, 42% female) were included in this analysis. Of these, 128 (45%) had public insurance. Publicly insured patients experienced a longer delay from surgery to hop test (8.3vs7.7 months, p = 0.009), attended overall fewer PT visits per week (0.92vs1.04, p = 0.005), with most of the decreased frequency occurring between weeks 7-24. Insurance status had a significant effect on the odds of passing the single leg hop test (2.72; 95%CI, 1.27-5.81)., Conclusion: Publicly insured patients average a lower number of weekly PT visits, experienced a longer delay from surgery to hop testing and were 2.7 times less likely to pass the single leg hop for distance test., Competing Interests: Declaration of competing interest We, the authors, affirm that we have no financial or commercial affiliations related to the performance or outcome of this manuscript., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era., Methods: We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups., Results: Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32-0.60, p < 0.001) with a longer median overall survival (OS) (35.9 months vs 12.1 months), 1-year OS of 71.6% vs 50.5% and 2-years OS of 56.5% vs 22.0% compared to those who did not. No significant interaction between nephrectomy and the overall five Meet-URO score risk groups was observed (p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 (p = 0.038) and associated with a longer OS for the first three prognostic groups (p < 0.001), but not for groups 4 and 5 (p = 0.54)., Conclusions: Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score., (© 2022. The Author(s).)

Background: Treatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors., Methods: By a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs., Results: The analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p < 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction <0.001), higher baseline IR values (NLR: p = 0.012, SII: p = 0.003, PLR: p = 0.003), increasing NLR and systemic immune-inflammatory index (SII) (i.e., NLR x platelets) Δ (p for interaction time-group = 0.0053 and 0.0435, respectively) were associated with disease progression. OS and PFS were significantly shorter in patients with baseline lower lymphocytes (p < 0.001 for both) and higher platelets (p = 0.004 and p < 0.001, respectively) alongside early neutrophils Δ (p = 0.046 and p = 0.033, respectively). Early neutrophils and NLR Δ were independent prognostic factors for both OS (p = 0.014 and p = 0.011, respectively) and PFS (p = 0.023 and p = 0.001, respectively), alongside baseline NLR (p < 0.001 for both) and other known prognostic variables., Conclusions: Early neutrophils and NLR Δ may represent new dynamic prognostic factors with clinical utility for on-treatment decisions., Competing Interests: SR received honoraria as a speaker at scientific events and travel accommodation from Amgen, GSK, BMS, and MSD. GB reports personal fees from AstraZeneca, Janssen-Cilag, Boehringer Ingelheim, Roche, and non-financial support from BMS, AstraZeneca, MedImmune, Pierre Fabre, and IPSEN. GF services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, and Merck and received travel accommodation from Astellas, Janssen, and Bayer. SB received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, and Novartis. DS received honoraria for the advisory board from Amgen, Jansen, MSD, BMS, Bayer, Astra Zeneca, Ipsen, Novartis, and Merck. UG serves as advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, and Sanofi, and received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS, IPSEN, Janssen, and Pfizer. PZ services advisory boards/consulting for Pfizer, BMS, MSD, IPSEN, Novartis, Roche, Amgen, AstraZeneca, Sanofi, Janssen, and Astellas. GPro received a personal fee for consulting or advisory role AstraZeneca, Bayer, BMS, Eisai, Janssen, Ipsen, Merck, MSD, Novartis, and Pfizer and a research grant from Astellas, Ipsen, Novartis. MSo received honoraria as consultant or advisory role from Janssen; grants for participation at scientific events from Ipsen, Janssen, Bristol Myers Squibb, Pfizer, Astellas Pharma, Sanofi, Roche, and Novartis; and research funding from Roche, Merck, Janssen. ACo receives speaker fees/grant consultancies from Astrazeneca, BMS, MSD, Roche, Novartis, and Astellas. FMo received grants from MSD and Pfizer. GR received honoraria for advisory boards or invited speaker fees from BMS, Astellas, Bayer, Ipsen, Novartis, Roche, and AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rebuzzi, Signori, Stellato, Santini, Maruzzo, De Giorgi, Pedrazzoli, Galli, Zucali, Fantinel, Carella, Procopio, Milella, Boccardo, Fratino, Sabbatini, Ricotta, Panni, Massari, Sorarù, Santoni, Cortellini, Prati, Soto Parra, Atzori, Di Napoli, Caffo, Messina, Morelli, Prati, Nolè, Vignani, Cavo, Roviello, Llaja Obispo, Porta, Buti, Fornarini and Banna.)

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion ( p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes ( p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods ( p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Aims: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1)., Methods: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed., Results: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC., Conclusion: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients., Patients and Methods: mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT., Results: The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72-1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55-1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively., Conclusions: This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need., Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites., Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS - mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups., Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations., Competing Interests: Conflict of interest statement: Dr Fornarini services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, and Merck, and received travel accommodation from Astellas, Janssen, and Bayer. Dr Buti received honoraria as a speaker at scientific events and in an advisory role by BMS, Pfizer; MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis. Dr Banna reports personal fees from AstraZeneca, Janssen-Cilag, Boehringer Ingelheim, Roche, and non-financial support from Bristol-Myers Squibb, AstraZeneca, MedImmune, Pierre Fabre, IPSEN, outside the submitted work. Dr De Giorgi services as an advisory/board member of Astellas, Bayer, Bristol-Myers Squibb, IPSEN, Janssen, Merck, Pfizer, and Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi, and travel/accommodations/expenses from Bristol-Myers Squibb, IPSEN, Janssen, and Pfizer. Dr Zucali services advisory boards/consulting for Pfizer, Bristol-Myers Squibb, MSD, IPSEN, Novartis, Roche, Amgen, AstraZeneca, Sanofi, Janssen, and Astellas. Dr Masini received personal fees as a speaker from Astellas, as a consultant from IPSEN, MSD, and Janssen, and for travel accommodation from BMS, Pfizer, Astellas, Janssen, and IPSEN. Dr Procopio services advisory boards/consulting for Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, IPSEN, Merk, MSD, Novartis, and Pfizer. Dr Cortellini receives speaker fees/grant consultancies from Astrazeneca, BMS, MSD, Roche, Novartis, and Astellas. Dr Morelli received grants from MSD and Pfizer. Dr Bersanelli received research funding to the institution from Roche, Pfizer, Seqirus UK, AstraZeneca, Bristol-Myers Squibb, Novartis, and Sanofi, and received personal fees for advisory role, copyright transfer, consultancies, and as speaker at scientific events from Sciclone Pharmaceuticals, Bristol-Myers Squibb, AstraZeneca, Pierre-Fabre, Novartis, and Pfizer. The other authors have no conflicts of interest to disclose., (© The Author(s), 2021.)

Background: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events., Patients and Methods: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported., Results: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3-2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5-3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated ( p =  0.009, p <  0.0001, p <  0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p =  0.52. The difference remained non-significant, considering confirmed COVID-19 only ( p =  0.33)., Conclusion: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection., Competing Interests: Conflict of interest statement: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study by Seqirus and Roche S.p.A.; the Federation also received funding during the conduct of the present study by Astra Zeneca, Bristol Myers Squibb (BMS), Sanofi. Melissa Bersanelli received funding for the present study by Seqirus and Roche S.p.A. (FICOG as Institution, no personal fees). She also received, outside the present work, research funding from Pfizer and Novartis (Institution), honoraria as speaker at scientific events (personal fees) by Astra Zeneca, Bristol Myers Squibb (BMS), Novartis and Pfizer; as consultant for advisory role (personal fees) by Novartis, BMS and Pfizer. Ugo De Giorgi received honoraria from AstraZeneca, Roche, MSD, Pfizer, GSK, Clovis, Incyte and research funding from Roche, AstraZeneca, MSD, Pfizer. Dr Di Maio reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Astellas, personal fees from Pfizer, personal fees from Eisai, personal fees from Takeda, grants from Tesaro GSK, outside the submitted work. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli Lilly, AstraZeneca and Novartis; he also received research funding from Novartis. Marcello Tiseo received honoraria (personal fees) by MSD, BMS, Boehringer (BI), Takeda, AstraZeneca, and research funding by AstraZeneca (Institution). Vieri Scotti participated, with personal fees, to advisory boards and speaker’s bureaus for Roche S.p.A. Dr Cortellini reports grants from AstraZeneca, grants from MSD, grants from BMS, grants from Roche, during the conduct of the study; grants from AstraZeneca, grants from MSD, grants from BMS, grants from Roche, grants from Novartis, outside the submitted work. Saverio Cinieri declared international board for Eli Lilly international. Paolo Andrea Zucali acts in a consultant or advisory role for Sanofi, BMS, Pfizer, MSD, Astellas, Janssen, Ipsen, Novartis, all outside the scope of work. Sergio Bracarda declares to have acted as advisory board member (uncompensated) for: Janssen, Astellas, Pfizer, MSD, BMS, Merck, AstraZeneca, AAA, Ipsen, Bayer, Roche/Genentech. Francesco Carozza declared personal fees from Janssen. Sara Pilotto reports personal fees from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Merk & Co, Roche, outside the submitted work. All remaining authors have declared no conflicts of interest., (© The Author(s), 2020.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region., Methods: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ 2 test for trends relative to the questions with 3 or more options., Results: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones., Conclusion: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of this study is to evaluate cardiotoxicity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer patients (pts) with cardiovascular comorbidities or coronary artery disease (CAD) risk factors., Patients & Methods: We prospectively analyzed pts receiving AA in order to evaluate correlations between cardiotoxicity onset and CAD risk factors or cardiovascular comorbidities., Results: Eighty-seven pts were enrolled, with median treatment duration of 9 months (1-44). At baseline, 84 pts (96%) had CAD risk factors. During treatment four pts (4; 6%) developed hypertension and 26 pts (30%) worsened the preexisting hypertension. Median left ventricular ejection fraction were 64 and 63% at baseline and after treatment, respectively., Conclusion: AA appears to be safe in pts with cardiovascular comorbidities or CAD risk factors.

Aims: This retrospective study aimed to investigate safety and efficacy of everolimus in patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease requiring dialysis., Patients & Methods: From November 2009 to December 2012, 11 mRCC patients undergoing dialysis were treated with everolimus after failure of anti-VEGF therapy at six Italian institutions. Patient characteristics, safety and outcomes were collected., Results: Progression-free survival and overall survival were determined using the Kaplan-Meier method. Median progression-free survival and overall survival were 9.01 and 15.7 months, respectively. No unexpected adverse events were reported., Conclusion: Everolimus appears to be safe in mRCC patients with renal impairment or end-stage renal disease requiring dialysis. Larger prospective studies are required to confirm these findings.

[-2]pro-prostate-specific antigen (2pPSA), a proform of PSA, is a new marker in patients at risk of prostate cancer. We explored the potential role of 2pPSA in the identification of patients with metastatic progression following radical prostatectomy for prostate cancer. Seventy-six patients with biochemical (PSA) recurrence following radical prostatectomy were studied retrospectively. Diagnostic imaging performed at the time of biochemical recurrence confirmed metastatic disease in 31 of the 76 patients. Serum samples were collected and stored at the time of imaging-confirmed metastatic progression or at the most recent procedure for patients with negative imaging. Median values of PSA, free PSA (fPSA), %fPSA, 2pPSA and prostate health index (PHI) were compared between metastatic and non-metastatic patients by the Mann-Whitney U test. The results of each test were then correlated with metastatic status by univariate and multivariate logistic regression analysis. PSA, fPSA, %fPSA, 2pPSA serum concentrations and PHI values were statistically significantly higher in patients with metastatic disease. Results of the multivariate analysis revealed that 2pPSA remained a statistically significant predictor of imaging-proven metastatic prostate cancer among patients with biochemical recurrence. At a cut-off value of 12.25 pg/ml, 2pPSA outperformed the other markers in terms of sensitivity and specificity (97 and 80%, respectively) with respect to imaging-confirmed metastatic progression. This is the first study suggesting that 2pPSA predicts diagnostic imaging-proven metastatic disease in previously resected prostate cancer patients with biochemical recurrence. Our results merit validation in a prospective study.

Central nervous system (brain or leptomeningeal) metastases (BLm) are considered rare in castration-resistant prostate cancer (CRPC) patients. Now that docetaxel has become the reference drug for first-line treatment of CRPC, patients whose disease is not controlled by hormonal manipulations may live much longer than before and have higher risk of developing BLm. We retrospectively reviewed the records of all patients with CRPC attending our centres from 2002 to 2010, and identified all of those who were diagnosed as having BLm and received (or were considered to have been eligible to receive) docetaxel-based treatment. We identified 31 cases of BLm (22 brain metastases and 9 leptomeningeal metastases) with an incidence of 3.3%. BLm-free survival was 43.5 months, and survival after BLm discovery was 4 months. With six patients surviving for more than 1 year after developing BLm, the projected 1-year BL-S rate was 25.8%. The findings of our study may be relevant in clinical practice as they indicate that incidence of BLm in CRPC patients in the docetaxel era seems to be higher than in historical reports, meaning that special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors because they may be related to BLm.

The autobiographical Implicit Association Test (aIAT) was recently introduced in this journal as a new and promising lie-detection tool. The initial report found 91% accuracy in determining which of two autobiographical events was true. It was suggested that the aIAT, unlike other lie-detection tests, is resistant to faking. We investigated whether participants can strategically alter their performance on the aIAT. Experiment 1 showed that participants guilty of a mock theft were able to obtain an innocent test outcome. Two additional experiments showed that guilty participants can fake the aIAT without prior experience with the aIAT and when a response deadline is imposed. The aIAT is subject to the same shortcomings as other lie-detection tests.