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The prognosis in the setting of metastatic castration-resistant prostate cancer patients (mCRPC) remains limited. Therefore, novel treatment strategies remain an unmet need. Antibody-drug conjugates (ADC) emerged as a new drug concept with the potential to deliver a cytotoxic payload with limited off-target toxicity and potentially bystander effect. Following the success of ADCs in breast cancer and urothelial tumours, their activity in prostate cancer is now under investigation. Thus, the aim of this systematic review was to identify published and ongoing prospective clinical trials regarding ADC treatment in prostate cancer. A systematic search of PubMed, MEDLINE, and Web of Science was conducted as per PRISMA guidelines to identify prospective clinical trials of ADCin prostate cancer. Trials are currently ongoing on ClinicalTrials.gov and in the EU. The Clinical Trials Register was also identified. Abstracts, publications in languages other than English, review articles, retrospective analyses, and phase I trials were excluded. A total of six phase I/II prospective clinical trials already published were included. Seven ongoing trials were also identified. All studies were in the refractory/advanced tumour setting, and two included only mCRPC patients. The ADC targets were prostate-specific membrane antigen (PSMA), trophoblast cell surface antigen-2 (TROP-2), six-transmembrane epithelial antigen of prostate-1 (STEAP-1), tissue factor (TF), delta-like protein 3 (DLL-3), B7-H3 family of proteins (B7-H3), and human epidermal growth factor receptor 2 (HER2). Regarding the efficacy of PSMA ADC treatment in the second-line or beyond mCRPC setting, a PSA ≥ 50% decline rate in 14% of all treated patients was reported. One patient achieved a complete response with TROP-2 ADC. Overall, a wide range of safety issues were raised, particularly in connection with neuropathy and hematologic toxicity. Novel therapies have been changing the scope of treatment in mCRPC. ADCs seem to provide efficacy benefits, even with potential toxicity. The results of most prospective ongoing studies are still awaited, and a longer follow-up time is warranted to evaluate the real impact of ADCs in PCa., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sardinha et al.)

Background: Immune checkpoint inhibitors (ICI) have emerged as active therapies in the management of advanced RCC. While multiple studies have shown clinical activity of ICIs in clear cell histologies, the evidence to support their use in non-clear cell (ncc) subtypes is based on smaller prospective trials and retrospective analyses., Objective: The objective of this review is to summarize the clinical outcomes of ICI-based therapies in ncc-subtypes and in tumors with sarcomatoid/rhabdoid features., Methods: We performed a systematic literature search using PubMed, Google Scholar and ASCO databases. The keywords "renal cell cancer" and "immune checkpoint inhibitors" and equivalents were used and all original publications between July 2016 and July 2021 were included., Results: We included a total of 14 publications, including two clinical trials and 12 case series. The most frequent histologies were papillary (up to 75-100%), unclassified (up to 34%) and chromophobe (up to 28%). ICI monotherapy showed some activity in both 1st and 2nd line with response rates up to 27%. ICI combination regimens yielded better activity than ICI monotherapy but, overall, a heterogeneous efficacy was noted across histologies. Overall, outcomes of ICIs were superior in tumors with sarcomatoid/rhabdoid features., Conclusion: The observed activity of ICI-based therapies was heterogeneous. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation., Competing Interests: Ana Filipa Palma dos Reis (has no conflict of interests to report), Diana Simão (has no conflict of interests to report), Thomas Odeny (has no conflict of interests to report), Chiara Rodrigues (has no conflict of interests to report), Mário Fontes (speaking role/advisory boards: Bristol Myers Squibb, Daiichi Sankyo, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Servier), Ricardo da Luz (has no conflict of interests to report), Rajasree Pia Chowdry (has no conflict of interests to report), Sarah J Welsh (has no conflict of interests to report), Channing Paller (has no conflict of interests to report), Pedro C. Barata consultant (Institution): Astellas; Eisai; Janssen, EMD Serono; Dendreon; Pfizer, Seattle Genetics, BMS, Bayer, Guardant Health; contracted research (Institution): AstraZeneca, Merck; research grant (Institution): BlueEarth Diagnostics; speaker’s bureau (Institution): Bayer, Caris, Pfizer., (© 2022 – The authors. Published by IOS Press.)