More than 7% of newly diagnosed prostate cancer (PCa) patients present with metastases,¹ where the recent introduction of highly sensitive diagnostic and staging modalities (ie, prostate multiparametric MRI and prostate- specific membrane antigen–positron emission tomography [PSMA- PET]) into clinical practice substantially increased the likelihood of identifying patients with advanced disease.² This phenomenon would make the interpretation of long-term data on treatment and outcomes in advanced PCa patients more challenging since available trials are based on patients diagnosed and staged using conventional imaging techniques.^3,4 Many of the abstracts presented during the advanced PCa poster session at the recent AUA 2024 annual meeting in San Antonio (Texas) focused on the impact of PSMA-PET in both primary and secondary PCa staging. Here, analyses from a multi-institutional collaboration aimed at verifying whether findings observed in the conventional imaging era are still applicable in patients staged with molecular imaging. The authors reported that among patients with lymph node invasion at radical prostatectomy (RP), those with suspicious nodal lesions at preoperative PSMA-PET (miN1) had, in contrast to what had been previously observed for cN1 patients,⁵ worse cancer control outcomes after surgery (ie, biochemical failure), with the presence of multiple visible spots being an independent predictor of worse prognosis. These findings, if confirmed with long-term outcomes, may provide precious insight into optimal patient selection for surgical treatment and the need for a multimodal approach. Indeed, the identification of patients harboring a locally advanced rather than a systemic disease remains a critical issue in patients with PCa for optimal treatment strategies. A collaborative initiative of the European Association of Urology Robotic Urology Section Scientific Working Group aimed to identify optimal candidates for androgen deprivation therapy (ADT) in patients with persistently elevated PSA after surgery, given the lack of prospective data on this specific entity. After an interaction analysis between treatment groups (postoperative ADT vs no ADT), the authors concluded that patients with an estimated 10-year cancer-specific mortality risk of ≥ 6%, calculated with a multivariable model including pathological information, were those who benefited the most from systemic treatment.

As previously mentioned, the introduction of highly sensitive staging modalities would lead to a higher number of patients diagnosed with metastatic hormone- sensitive PCa (mHSPC). The latter represents a unique entity, given patients’ higher risk of ultimately dying from PCa and the introduction of novel antiandrogen-targeted agents into their treatment paradigm. Using real-world data, the European Network of Excellence for Big Data in Prostate Cancer (PIONEER) described the demographics, clinical characteristics, treatment patterns, and clinical outcomes of a large cohort of 94,261 patients with mHSPC. The main report was the lack of adherence to guideline-recommended treatment in approximately one-third of patients. Although real-world data provide a snapshot of what is happening in the community, interpretation of such data requires caution, as the actual percentage of patients receiving guideline-recommended treatment may have been diluted by the inclusion of elderly or comorbid patients in whom optimal treatment strategies may not be suitable. In this context, the increased risk of toxicities due to dose intensification treatment should not be underestimated. Results from 7 trials identified in the Yale University Open Data Access (YODA) repository evaluating treatment with abiraterone acetate (AA) in patients with metastatic castration-sensitive or castration-resistant PCa showed that AA did not significantly affect erectile function or sexual satisfaction assessed by the Functional Assessment of Cancer Therapy- Prostate questionnaire.

When discussing the potential benefit of local treatment in mHSPC,³ the role of cytoreductive RP in selected low metastatic burden patients represents a controversial topic. Here, a group of investigators evaluated the pathological response in patients treated with cytoreductive RP after neoadjuvant therapies. All patients received treatment with ADT (18.5%) vs ADT + AA (24.7%) vs ADT + apalutamide (24.7%) vs ADT + enzalutamide (9.9%) vs ADT + docetaxel (22.2%) prior to RP. The authors reported the presence of lymph node invasion in 42 (45.2%) patients and local recurrence in 2 (2.2%) patients, with Clavien-Dindo grade III to IV complications observed in 15 (16.1%) patients. Overall, ADT + apalutamide and ADT + docetaxel were associated with the lowest risk of lymph node invasion. The authors concluded that cytoreductive RP should be considered as an option for local treatment within a multidisciplinary discussion.

In conclusion, the advanced PCa abstract session showed that the management of these patients is an evolving field with several implications relative to the introduction of new imaging modalities and optimal treatment strategies still unclear.