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Davide Bimbatti,1 Eleonora Lai,1,2 Francesco Pierantoni,2,3 Marco Maruzzo,1 Aichi Msaki,1 Chiara De Toni,1 Michele Dionese,1,2 Alessandra Feltrin,4 Umberto Basso,1 Vittorina Zagonel1 1Oncology 1 Unit, Istituto Oncologico Veneto IOV – IRCCS, Padua, Italy; 2Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy; 3Oncology 3 Unit, Istituto Oncologico Veneto IOV – IRCCS, Padua, Italy; 4Hospital Psychology Unit, Istituto Oncologico Veneto IOV – IRCCS, Padua, ItalyCorrespondence: Davide Bimbatti, Oncology 1 Unit, Istituto Oncologico Veneto, IOV - IRCCS, via Gattamelata 64, Padova, 35128, Italy, Email Davide.bimbatti@iov.veneto.itPurpose: Testicular cancer (TC) is the most common solid tumor in young adults. 95% of patients are cured, but they may experience late adverse effects (anxiety, fear of recurrence, and sexual dysfunction) with an impact on daily life. We attempted to assess Patient Reported Outcomes (PROMs), long-term sexual disorders, and difficulties in achieving fatherhood in a cohort of TC survivors, as well as their possible correlation with previous cancer treatments.Methods: Different questionnaires, such as the Impact of Cancer (IOC) and the Body Image Scale (BIS), were used to investigate the distinct areas of the PROMs. International Index of Erectile Function (IIEF15) and the Premature Ejaculation Diagnostic Tool (PEDT) focused on sexuality and fertility. Patients were prospectively recruited between February 2020 and February 2022.Results: 144 participants completed all the questionnaires. Results showed a good QoL, a moderate fear of TC recurrence, a good satisfaction with their personal body image, low incidence of premature ejaculation and erectile dysfunction. 19.5% of patients who had a testicular implant reported general dissatisfaction. Only 18% of patients had unsuccessfully attempted fatherhood, while the majority had not yet tried, and 23.4% succeeded. A low percentage of patients used procedures assisted reproduction and adoption.Conclusion: This trial supports the use of various questionnaires as a multifactorial tool capable of investigating all the aspects of long-term cancer survivorship. The assessment of medical and psychosocial sequelae is an essential part of patient care and is important for the development of a comprehensive care plan for TC survivors.Keywords: testis cancer, testis cancer survivor, testis cancer PROMs, testis cancer fertility

Rationale: Metastatic castration-resistant prostate cancer has a poor prognosis especially when harboring DNA damage repair gene mutations, nevertheless, in the case of pathogenic BRCA gene mutations, PARPi demonstrated a survival benefit and is a validated treatment. Nowadays, there is no data regarding unusual metastases after these drugs. Cutaneous metastases appear rarely in prostate cancer and were associated with a worse prognosis. Moreover, there are no consolidated data concerning skin tropism of prostate cancer cells, neither in the case of BRCA-associated cancers., Patient Concerns: Here, we report the case of a patient with a long history of BRCA1-mutated metastatic castration-resistant prostate cancer who developed a skin lesion on the scalp while on his fifth line of systemic therapy with olaparib. After a complete radical surgical excision, the pathology report showed prostate cancer localization., Diagnoses: A diagnosis of skin metastasis from prostate cancer was reported., Outcomes: The patient then continued olaparib therapy; after 7 months from excision, he experienced further bone and biochemical progression but not cutaneous progression., Lessons: A literature review of all reported cases of cutaneous metastasis in prostate cancer was conducted to shed light on the incidence, clinical presentation, diagnosis, treatment, and prognosis of this entity. We also reviewed published cases of skin metastasis in BRCA-associated cancers with an effort to correlate skin involvement with PARPi treatment, BRCAness status, and prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aim: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic urothelial carcinoma (mUC). However, they could be associated with immune-related adverse events (irAEs), which may be clinically significant. Identifying clinical characteristics that may be associated with a higher risk of irAEs is of great importance., Patients and Methods: We retrospectively collected data from all patients who received anti-PD1 or anti-PD-L1 for metastatic UC at our Institution from January 2017 to December 2022. Patients were dichotomized according to baseline neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) values. We performed univariate and multivariate logistic regression to determine the association between baseline characteristics and the development of irAEs., Results: A total of 119 patients were identified. At a median follow-up of 29.6 months, 96 patients progressed and 82 died. Forty-five patients developed irAEs of any grade, 8 patients developed grade 3 toxicities. In the univariate analysis PS of 0 (p<0.01), baseline NLR <3.52, baseline PLR <194 (p=0.04) and baseline SII <906 (p=0.01) were significantly associated with a higher risk of developing irAEs, whereas in the multivariate analysis only PS=0 (p<0.01) and NLR <3.52 (p=0.03) maintained their correlation. Median progression-free survival (mPFS) and overall survival (mOS) were significantly longer in patients with NLR <3 (mPFS 3.8 vs. 2.6 months, p=0.01; mOS 15.3 vs. 5.6 months, p=0.002) and PS=0 (mPFS 4.8 vs. 2.1 months, p<0.001; mOS 15.3 vs. 3.8 months, p<0.001)., Conclusion: Low baseline NLR, PLR, and SII and good PS are associated with a higher risk of developing irAEs in patients treated with ICIs for mUC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pembrolizumab/Axitinib combination is approved as first-line therapy in mRCC. The aim of this study is to evaluate outcomes of PAXI combo in the real-world in Italy., Methods: This is a prospective study including patients diagnosed with mRCC who received combination as first-line therapy in recruiting Italian Centers. Data about patient characteristics, safety and outcome were collected., Results: 170 pts have been treated from December 2020 to September 2023. The majority had clear-cell histology (83%). Sarcomatoid feature was present in 33%of available cases. About one half of patients (55%) had synchronous metastasis. In 58% of cases nephrectomy was performed, of which 27% were cytoreductive and 4% were deferred nephrectomies. Lung metastases were identified in 106 patients (62%), bone and liver involvement in 66 and 29 patients (38.8% and 17.1%) respectively. Stratifying by IMDC criteria, 32 patients (18.8%) were at favorable-risk, 106 (62.4%) at intermediate-risk, and 32 (18.8%) at poor-risk. At time of analysis, treatment was ongoing in 49% of patients. Progression occurred in 45% of patients. Median PFS was 19.2 months (95% CI: 15-NR). With a median follow-up of 19.3 months (range 1.3-34.5), at 24-months and 36-months landmark analysis 62% (95% CI, 53-70) and 58% (95% CI, 47-69) of treated patients are still alive respectively. Disease control rate was achieved in 84.6% of patients: 4.3% reached a complete response, 52% had a partial response and 28.8% a stable disease. Primary progression was observed in 15.3% of patients. In the multivariate analysis, the prognostic significance of age ≥ 65 years, non-clear cell histology, IMDC score, and adverse events and gender interaction as predictors of worse OS were confirmed., Conclusion: This is the first available prospective study on first-line Pembrolizumab/Axitinib combination in real world scenario. Our findings support the effectiveness and safety of first-line this combination in mRCC and reveal that gender emerged as a prognostic factor in relation to the occurrence of adverse events., Competing Interests: Disclosure 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 paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Introduction: Evaluation of tumor response according only to dimensional criteria may underestimate treatment benefit in patients treated for metastatic renal cell carcinoma (RCC). In this study we evaluated the role of lesion enhancement modifications and Choi criteria in patients affected by renal cell carcinoma treated with immunotherapy., Methods: We collected data of 60 consecutive patients (with a total of 154 measurable lesions) treated with immunotherapy (nivolumab or ipilimumab plus nivolumab) at a single Institution. We evaluated tumour response using both RECIST1.1 criteria and Choi criteria at the first radiological assessment; we subsequently associated response with progression free survival and overall survival., Results: Choi criteria found a higher rate of objective response compared to RECIST criteria (38.3% vs 18.3%). An objective response according to both criteria was associated with longer progression free survival and overall survival. Response rate for Choi did not vary according to lesion site., Conclusion: Choi criteria seemed to be able to predict clinical benefit in a higher proportion of patients with renal cell carcinoma treated with immunotherapy than RECIST criteria. Partial response according to RECIST was confirmed as a predictor of longer progression-free survival and overall survival., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: A low fT3/fT4 ratio has been associated with a poorer prognosis in patients treated for different solid malignancies. However, the prognostic role of baseline thyroid function in patients with metastatic urothelial carcinoma (mUC) has not yet been established., Patients and Methods: We analyzed 72 consecutive immunotherapy-treated patients with mUC from a single institution. We recorded clinical data, baseline blood test results, and oncological outcomes. We stratified patients into three groups according to the fT3/fT4 ratio value and analyzed differences in progression-free survival (PFS), overall survival (OS), and radiological response in the three groups. We also conducted univariate and multivariate analyses to identify prognostic factors for PFS and OS., Results: The median PFS in the low, intermediate, and high fT3/fT4 ratio groups was 2.2, 4.1, and 8.2 months, respectively (P < 0.01). The median OS in the low, intermediate, and high fT3/fT4 groups was 3.6, 10.3, and 19.1 months, respectively (P < .01). The low fT3/fT4 ratio maintained its prognostic role independently of other prognostic factors. Patients with a high fT3/fT4 ratio had an increased radiological response., Conclusion: Thyroid hormone impairment, as measured by the fT3/fT4 ratio, is a strong prognostic factor in patients treated with immunotherapy for urothelial carcinoma., Competing Interests: Disclosure This research received “Ricerca Corrente” funding from the Italian Ministry of Health to cover publication costs., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced nccRCC patients treated at our institute., Patients and Methods: We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS., Results: Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value., Conclusion: Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited.

Background: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations. This sub-analysis is focused on the role of upfront or delayed partial or radical CN in three geographical areas (Western Europe, Eastern Europe, America/Asia)., Methods: We conducted a multicenter retrospective observational study in mRCC patients treated with first-line immune combinations from 55 centers in 19 countries. From 1152 patients in the ARON-1 dataset, we selected 651 patients with de novo mRCC. 255 patients (39%) had undergone CN, partial in 14% and radical in 86% of cases; 396 patients (61%) received first-line immune-combinations without previous nephrectomy., Results: Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months and not reached (NR) in the CN subgroup and 24.0 months in the no CN subgroup, respectively (P<0.001). Median OS from the start of first-line therapy was NR in patients who underwent CN and 22.4 months in the no CN subgroup (P<0.001). Patients who underwent CN reported longer OS compared to no CN in all the three geographical areas., Conclusions: No significant differences in terms of patients' outcome seem to clearly emerge, even if the rate CN and the choice of the type of first-line immune-based combination varies across the different Cancer Centers participating in the ARON-1 project.

Aims: Inflammation indexes had been associated with overall survival (OS) and immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs)., Materials & Methods: in 72 patients treated with ICIs for metastatic urothelial carcinoma (mUC) we evaluate differences in OS, response rate and toxicities, according to baseline inflammation indexes values., Results: neutrophil-to-lymphocite ratio (NLR) <3 was associated to longer progression-free survival (PFS; 4.9 vs 3.1 months) and OS (15.7 vs 7.6 months); monocyte-to-lymphocite ratio (MLR) <0.4 was associated to longer PFS (4.6 vs 2.8 months). Overall response rate (ORR), disease control rate (DCR) were higher in these patients. Patients with an irAE had longer PFS and OS., Conclusion: baseline inflammatory indexes are prognostic for mUC patients treated with ICIs., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 The Authors.)