PARIS — Should clinicians promote active surveillance for non–muscle-invasive bladder tumors (NMIBT) and establish it as a comprehensive management approach, as with prostate and kidney cancers?
During the 117th congress of the French Association of Urology (AFU), Benjamin Pradère, MD, urologic surgeon at Croix du Sud Clinic in Quint Fonsegrives, France, advocated for this approach, suggesting that the use of biomarkers could enhance its effectiveness.
In managing precancerous lesions like NMIBT, "implementing active surveillance is a safe, cost-effective option that improves the quality of life. However, it requires careful patient selection, proper information, and relevant follow-up," said Pradère, who is a member of the AFU Cancer Committee (CCAFU).
Low-Grade Tumors
NMIBTs are precancerous lesions and constitute 70%-80% of diagnosed bladder tumors. The remaining tumors are more severe invasive tumors (IMBT) that infiltrate deep tissues. NMIBTs, however, entail a high risk for recurrence (reaching 80% after endoscopic resection), as well as a high risk for progression.
As a result, the diagnosis of NMIBT involves follow-up that significantly impacts patients' quality of life due to repeated cystoscopies and endovesical treatments. "Tumors with the most impact are low-grade Ta tumors", with longer-term monitoring required for these low-risk tumors.
Hematuria is the most frequent clinical sign. NMIBT diagnosis occurs after endoscopic tumor resection via transurethral resection, followed by an anatomopathological analysis to determine cell grade and tumor stage. Treatment depends on the risk of recurrence and progression, as well as the risk of therapeutic failure after the initial resection.
Risk stratification distinguishes the following four levels:
- Low-risk tumors: Low-grade pTa urothelial tumors, unifocal, < 3 cm, no history of bladder tumors. Low risk of recurrence and progression.
- Intermediate-risk tumors: Other low-grade pTa urothelial tumors with no high-risk criteria. Low risk of progression but high risk of recurrence.
- High-risk tumors: Tumors with at least one risk factor: Stage pT1, high grade, presence of carcinoma in situ. High risks of progression and recurrence.
- Very high-risk tumors: Tumors combining all risk factors (pT1 grade with carcinoma in situ). Very high and early risk of progression.
The recurrence rate for low-grade tumors is 50%, but recurrences are "almost always low-grade and rarely invade the basement membrane," said Pradère. Implementing active surveillance to limit surgical intervention to more advanced forms seems to be relevant for these tumors.
Cystoscopy Every 3 Months
According to CCAFU recommendations, "active surveillance is a therapeutic alternative that can be proposed for patients with recurrent low-risk NMIBT after the initial diagnosis." Criteria include low-grade pTa, fewer than five tumors, size ≤ 15 mm, negative urinary cytology, asymptomatic nature, and the patient's acceptance of closer monitoring.
While active surveillance has become the standard treatment for low-risk prostate cancer, this therapeutic option remains marginal in bladder cancer, as in kidney cancer. The goal is to defer or avoid surgical treatment by closely monitoring the natural progression of the disease.
For NMIBTs, follow-up modalities are not yet specifically recommended because of a lack of data, said Pradère. According to a consensus, cystoscopy should be repeated every 3 months for a year and then every 6 months. Unlike standard follow-up, it includes cytology "to not miss the transition to high grade."
CCAFU recommends discontinuing active surveillance if any of the following criteria are present:
- More than 10 lesions
- Size > 30 mm
- Positive cytology
- Symptoms (hematuria, micturition disorders, and recurring infections).
Literature on the benefits of active surveillance in bladder tumors is still limited. Only seven studies are available. Overall, for nearly 600 included patients, tumors progressed in about 12% of cases. Progression to invasive tumors occurred in 0.8% of patients (n = 5).
13 Months’ Surveillance
According to a long-term study (median follow-up of 38 months), patients mostly exit active surveillance in the first year. The median duration of active surveillance is 13 months. Active surveillance is discontinued to surgically treat tumors that turn out to be low-grade Ta tumors in 70% of cases.
The following factors predicting recurrence and progression of tumors have been identified: Multiple tumors, early recurrence (within a year of initial diagnosis), frequent recurrence (more than one recurrence per year), tumors > 3 cm, and failure of previous endovesical treatment.
Recent studies have shown that with at least three of these recurrence and progression factors, the median duration under active surveillance is 15 months compared with 28 months in the absence of such factors. "Considering these factors, it is possible to assess the benefit of active surveillance for the patient," said Pradère.
If active surveillance for bladder tumors is still not widely practiced, then the contribution of imaging (MRI and ultrasound) and biomarkers could promote its adoption. "The use of biomarkers should change the game and encourage active surveillance in patients with small polyps," said Pradère.
ADXBladder Test Utility
A study highlighted the importance of evaluating Minichromosome Maintenance Protein 5 expression during active surveillance using the ADXBladder ELISA test on a urine sample. This test is usually used in bladder cancer diagnosis.
"This study showed that a negative result in two consecutive tests during active surveillance is associated with an almost zero recurrence risk. After two negative tests, most patients do not exit active surveillance," said Pradère. But the positive predictive value of biomarkers remains low for low-grade tumors.
The future of active surveillance in bladder cancer should involve better patient selection that relies on risk factors, enhanced modalities through imaging and biomarkers, and the advent of artificial intelligence to analyze cystoscopy results, concluded Pradère.
This article was translated from the Medscape French edition.