A meta-analysis of over 9,500 patients in major prostate cancer trials, including the pivotal VISION and PSMA-4 trials for radioligand therapy, shows significant underrepresentation of Black and Hispanic patients. This creates a critical evidence gap when applying these therapies to diverse real-world populations.

The debate over the STAMPEDE and ENSA-RAD trials stems from a misunderstanding. They aren't contradictory but study different cohorts within the "high-risk" category. STAMPEDE focused on the highest-risk patients, while ENSA-RAD included a broader group. Combining their data could provide a more nuanced treatment approach.

While PSMA PET scans are more sensitive, they create a clinical dilemma because pivotal trials defining treatment efficacy were based on conventional imaging (CT/bone scans). This forces oncologists to either re-image patients with older technology to match trial criteria or make treatment decisions based on PET data that lacks a clear evidence-based framework for response assessment.

After years of successfully intensifying hormonal therapy, the focus in prostate cancer is shifting toward de-intensification. Researchers are exploring intermittent therapy for top responders and developing non-hormonal approaches like radioligands to spare patients the chronic, life-altering side effects of permanent castration.

Landmark discoveries, like EGFR mutations, didn't start in a lab but with astute oncologists noticing patterns in how some patients responded to treatment while others didn't. This highlights that every patient interaction is a research opportunity, offering clues that can lead to the next scientific breakthrough.

Experts believe molecular tests like Decipher and PTEN status are superior to simply counting bone lesions for guiding treatment. While not yet standard practice for all decisions, this represents a significant shift towards using underlying tumor biology to determine therapy, like adding docetaxel.

Recent phase 3 trial data highlights a significant gap in care for metastatic castration-resistant prostate cancer (mCRPC). Despite clear guideline recommendations, only about half of patients in the trial received bone-targeted agents, exposing a concerning real-world trend of underutilization of standard-of-care supportive therapy.

When managing toxicities from trastuzumab deruxtecan (TDXD) in urothelial cancer, clinicians should refer to established protocols and literature from breast cancer, where experience is more extensive. This cross-disciplinary approach is necessary for managing side effects like nausea, vomiting, and lung disease until more bladder cancer-specific data becomes available.

As multiple effective Antibody-Drug Conjugates (ADCs) become available, the primary clinical challenge is no longer *if* they work, but *how* to use them best. Key unanswered questions involve optimal sequencing, dosing for treatment versus maintenance, and overall length of therapy, mirroring issues already seen in breast cancer.