The consensus for "event-free survival" (EFS) in bladder-sparing trials is now highly inclusive, counting even high-grade superficial (non-muscle invasive) relapses as events. This is a deliberately conservative choice to maximize patient safety and preempt the risk of these relapses leading to metastasis.

Experts caution that the new consensus definition of cCR, combining imaging and cystoscopy, is for clinical trials only. Applying it prematurely in routine practice could harm patients, as its correlation with true pathologic response is still being validated with modern therapies.

The trial's 57.1% pathologic complete response (pCR) rate is deceptively conservative. It categorized patients who responded well but declined surgery as non-responders, suggesting the treatment's true biological efficacy is even higher than the already impressive reported figure.

A positive ctDNA test indicating minimal residual disease is strongly linked to recurrence. This expert argues clinicians have an obligation to act on this information, even without definitive guidelines. Framing inaction as unacceptable challenges the passive "wait-and-see" approach.

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.

The InVigor11 study was the first to show that detecting recurrence via a ctDNA test before it's visible on scans is not just a prognostic sign, but an actionable clinical state. Intervening with therapy at this early stage was proven to improve patient outcomes, establishing a new paradigm for cancer surveillance.

The main barrier to widespread ctDNA use is not its proven ability to predict who will recur (prognostic value). The challenge is the emerging, but not yet definitive, data on its ability to predict a patient's response to a specific therapy (predictive value).

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.

While a positive ctDNA test clearly signals the need for adjuvant therapy, a negative result is less actionable for deciding initial treatment. The key prognostic value comes from being *serially* undetectable over time, information that is not available when the immediate post-surgery treatment decision must be made.