Metastatic hormone-sensitive prostate cancer (mHSPC) is a disease state characterized by the presence of distant metastases detectable on conventional imaging while the tumor remains responsive to androgen deprivation therapy (ADT). It represents an earlier, treatment-sensitive phase that precedes the development of metastatic castration-resistant prostate cancer (mCRPC), the terminal stage of the disease. The addition of therapies beyond traditional ADT to achieve more sustained tumor regression by combining different mechanisms of action and targeting different cancer fuelling pathways has spurred the concept of treatment intensification in prostate cancer. This approach may involve the addition of androgen receptor pathway inhibitors (ARPIs) to ADT-hereafter referred to as "treatment intensification"-or the addition of ARPIs plus chemotherapy to ADT-hereafter referred to as "treatment optimization." Randomized controlled trials have consistently shown improved patient outcomes with the evolution from ADT alone to ADT plus ARPI, and more recently to ADT plus ARPI plus docetaxel, and demonstrated that treatment intensification decisions in mHSPC have clinically meaningful implications. However, in the absence of comparative efficacy data between therapy options, the treatment choice for a given patient will depend on patient- and disease-related factors, with the goal of improving outcomes while minimizing the cumulative toxicity of therapies, particularly when using combination strategies. In this article, a panel of 28 experts-8 urologists and 20 oncologists-with recognized experience and expertise in the management of advanced prostate cancer discussed the role of treatment intensification in mHSPC and which patients are more likely to benefit from each treatment strategy.
Advances in therapy. 2026 May 23 [Epub ahead of print]
André Mansinho, João Carlos Gramaça, Rodrigo Ramos, Pedro Miguel Baltazar, José Palma Dos Reis, Ricardo Fernandes, Mariana Malheiro, Alina Rosinha, Sofia Amorim, Ricardo Borges, Isaac Braga, Andreia Capela, Diogo Nunes Carneiro, Rui Dinis, André Ferreira, Arnaldo Figueiredo, Sílvia Lopes, Pedro Silvestre Madeira, Helena Magalhães, Hélder Mansinho, Sara Meireles, Carolina Pereira, Cidália Pinto, Chiara Rodrigues, Ana Spencer, Carolina Carvalho, Tiago Tomás, Carlos Rabaça
START Lisbon, Unidade Local de Saúde Santa Maria, Lisbon, Portugal. ., Medical Oncology Unit, Unidade Local de Saúde São José, Lisbon, Portugal., Urology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal., iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal., Unidade Local de Saúde Santa Maria, Lisbon, Portugal., Unidade Local de Saúde de Braga, Braga, Portugal., CUF Tejo, Lisbon, Portugal., Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal., Unidade Local de Saúde Entre Douro e Vouga, Santa Maria da Feira, Portugal., Unidade Local de Saúde da Região de Leiria, Leiria, Portugal., Unidade Local de Saúde Gaia e Espinho, Vila Nova de Gaia, Portugal., Urology Department, Unidade Local de Saúde de Santo António, Porto, Portugal., Hospital do Espírito Santo de Évora, Unidade Local de Saúde do Alentejo Central, Évora, Portugal., Hospital de Santo André, Unidade Local de Saúde da Região de Leiria, Leiria, Portugal., Coimbra Hospital and University Centre, Unidade Local de Saúde de Coimbra, Coimbra, Portugal., Unidade Local de Saúde de Santo António, Porto, Portugal., Serviço de Oncologia Médica, Instituto Português de Oncologia de Coimbra Francisco Gentil, Coimbra, Portugal., Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal., Hospital Garcia de Orta, Unidade Local de Saúde Almada Seixal, Almada, Portugal., Unidade Local de Saúde São João, Porto, Portugal., Serviço de Oncologia Médica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal., Unidade Local de Saúde do Algarve, Faro, Portugal., Unidade de Urologia, Fundação Champalimaud, Lisbon, Portugal., Hospital de Cascais Dr. José de Almeida, Alcabideche, Portugal., Hospital de Guimarães, Unidade Local de Saúde Alto Ave, Guimarães, Portugal., Hospital Prof. Dr. Fernando Fonseca, Unidade Local de Saúde Amadora/Sintra, Amadora, Portugal., Serviço de Urologia, Instituto Português de Oncologia de Coimbra Francisco Gentil, Coimbra, Portugal.