The Rampart study's main contribution wasn't its specific drug data, but that it became the second positive trial in the adjuvant kidney cancer space. This balanced the 'scorecard' against multiple negative trials, reinforcing the general principle that early immune therapy is beneficial.

A key hypothesis for why docetaxel showed better overall survival than lutetium in the PLUTO trial is that patients treated with lutetium upfront may become unfit for subsequent chemotherapy. This highlights a critical factor in trial design: the planned therapeutic sequence and a patient's ability to receive later-line treatments significantly impact survival outcomes.

Despite exciting early efficacy data for in vivo CAR-T therapies, the modality's future hinges on the critical unanswered question of durability. How long the therapeutic effects last, for which there is little data, will ultimately determine its clinical viability and applications in cancer versus autoimmune diseases.

The lack of a placebo arm in some adjuvant trials is not necessarily a fatal flaw. One expert view is that it mirrors real-world practice where treatments are known. This perspective places trust in the investigators' ability to assess disease progression accurately without blinding.

In adjuvant bladder cancer trials, ctDNA status is both prognostic and predictive. Patients with positive ctDNA after surgery are at high risk of relapse but benefit from immune checkpoint inhibitors. Conversely, ctDNA-negative patients have a lower risk and derive no benefit, making ctDNA a critical tool to avoid unnecessary, toxic therapy.

An expert argues forcefully that the PD-L1 biomarker should be "ditched" in bladder cancer. Citing its repeated failure to predict overall survival benefit across multiple major trials, it is deemed an oversimplified and unreliable tool that leads to both over- and under-treatment of patients.

Sepsis is not a monolithic condition. The failure of more than 100 immunomodulatory drug trials is likely because they treated all patients the same. The future of sepsis treatment mirrors oncology: subtyping patients based on their specific inflammatory profile to match them with a targeted therapy.

In high-risk non-muscle invasive bladder cancer (NMIBC), trials like CREST and POTOMAC show adding a systemic immune checkpoint inhibitor to BCG therapy introduces significant toxicity. The benefit is primarily in local control, which may not justify the risk, especially with other effective intravesical options available.

The interpretation of ctDNA is context-dependent. Unlike in the adjuvant setting, in the neoadjuvant setting, remaining ctDNA positive post-treatment signifies that the current therapy has failed. These high-risk patients need a different therapeutic approach, not an extension of the ineffective one.