Oncofertility in Women with Renal Cell Carcinoma in the Immune Checkpoint Inhibitors Era: A Multidisciplinary Perspective

<b>Background/Objectives</b>: Renal cell carcinoma (RCC) care has been reshaped by immune checkpoint inhibitors (ICIs), now used across adjuvant and metastatic settings as PD-1/PD-L1 blockade alone, combined with anti-CTLA-4 agents, or in combination with vascular endothelial growth factor (VEGF)-targeting tyrosine kinase inhibitors (TKIs). As survival improves and systemic therapy courses extend, survivorship priorities-including fertility preservation, reproductive endocrine health, contraception, and pregnancy counselling-become increasingly relevant, even though RCC-specific oncofertility evidence remains sparse. This review examines the biological rationale and clinical considerations underpinning reproductive counselling for women of reproductive age exposed to ICIs (alone or with TKIs) in RCC. <b>Methods</b>: A narrative review was conducted in accordance with the SANRA framework, integrating targeted PubMed/MEDLINE searches up to 20 February 2026 and consultation of regulatory product labels to synthesize mechanistic, clinical, and safety data relevant to fertility, endocrine function, contraception, pregnancy, and breastfeeding in RCC. <b>Results</b>: We delineate the contemporary RCC treatment landscape to identify feasible timepoints for fertility preservation discussions and propose a pragmatic, implementation-oriented counselling framework that distinguishes evidence-secure recommendations (pregnancy avoidance during therapy, endocrine monitoring, agent-specific washout) from extrapolative domains (long-term ovarian reserve effects and post-ICI periconception safety beyond label intervals). <b>Conclusions</b>: By integrating a 'multi-hit' biological rationale, treatment context, and available human data, this review highlights RCC-specific research priorities while supporting transparent, evidence-aligned, and multidisciplinary counselling for both fertility preservation and pregnancy safety in the ICI era.

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Publication Details

Journal
Journal of Clinical Medicine
Published
2026-03-23
DOI
https://doi.org/10.3390/jcm15062452
Primary Topic
Reproductive Biology and Fertility
Type
article
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article

Oncofertility in Women with Renal Cell Carcinoma in the Immune Checkpoint Inhibitors Era: A Multidisciplinary Perspective

Linda Cipriani, Pietro Piazza, Antonio Raffone, Manuela Maletta et al.
Journal of Clinical Medicine
Reproductive Biology and Fertility
article

Oncofertility in Women with Renal Cell Carcinoma in the Immune Checkpoint Inhibitors Era: A Multidisciplinary Perspective

Linda Cipriani, Pietro Piazza, Antonio Raffone, Manuela Maletta, Stefano Ferla, L. Cobellis, Michele Miscia, Federica Cortese, Veronica Mollica, Enrico Pazzaglia, Irene Pesaresi, Maria Perucci, Renato Seracchioli, Diego Raimondo
article en

Abstract

<b>Background/Objectives</b>: Renal cell carcinoma (RCC) care has been reshaped by immune checkpoint inhibitors (ICIs), now used across adjuvant and metastatic settings as PD-1/PD-L1 blockade alone, combined with anti-CTLA-4 agents, or in combination with vascular endothelial growth factor (VEGF)-targeting tyrosine kinase inhibitors (TKIs). As survival improves and systemic therapy courses extend, survivorship priorities-including fertility preservation, reproductive endocrine health, contraception, and pregnancy counselling-become increasingly relevant, even though RCC-specific oncofertility evidence remains sparse. This review examines the biological rationale and clinical considerations underpinning reproductive counselling for women of reproductive age exposed to ICIs (alone or with TKIs) in RCC. <b>Methods</b>: A narrative review was conducted in accordance with the SANRA framework, integrating targeted PubMed/MEDLINE searches up to 20 February 2026 and consultation of regulatory product labels to synthesize mechanistic, clinical, and safety data relevant to fertility, endocrine function, contraception, pregnancy, and breastfeeding in RCC. <b>Results</b>: We delineate the contemporary RCC treatment landscape to identify feasible timepoints for fertility preservation discussions and propose a pragmatic, implementation-oriented counselling framework that distinguishes evidence-secure recommendations (pregnancy avoidance during therapy, endocrine monitoring, agent-specific washout) from extrapolative domains (long-term ovarian reserve effects and post-ICI periconception safety beyond label intervals). <b>Conclusions</b>: By integrating a 'multi-hit' biological rationale, treatment context, and available human data, this review highlights RCC-specific research priorities while supporting transparent, evidence-aligned, and multidisciplinary counselling for both fertility preservation and pregnancy safety in the ICI era.

Journal of Clinical MedicineVol. 15(6)
Humanitas University (IT), University of Campania "Luigi Vanvitelli" (IT), Azienda USL di Bologna (IT), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 15%
Reproductive Biology and Fertility
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