According to IBCG, the prognosis for IR-NMIBC is stratified based on key risk factors, including early recurrence (within less than 1 year), frequent recurrence (more than one recurrence per year), tumor multifocality, tumor size (≥3 cm), and recurrence despite prior intravesical treatment.
By stratifying our cohort using the IBCG prognostic risk factors, our objective was to identify which IR-NMIBC patients potentially fit for AS had a higher risk of subsequent recurrence. All patients fulfilled the criteria for enrollment for AS (≤5 suspicious lesions, no macrohematuria as presenting symptom, negative urine cytology collected before surgery, lesions ≤1cm in diameter) at the index transurethral resection of bladder tumor (TURBT), which was defined as the TURBT performed at our center where the LG IR-NMIBC was defined and from which the follow-up started.
Then, patients were stratified according to the IBCG scoring algorithm based on the number of risk features they harbored (0, 1–2, and≥3 risk factors) in reference to the index TURBT:
- Frequent recurrence (defined as more than 1 recurrence/year)
- Early recurrence (defined as a recurrence which occurs earlier than 1 year)
- Recurrence despite prior intravesical instillations
- Multifocality (>1 lesion)
Kaplan Meier curves were used to estimate the 1 and 3-year recurrence-free survival (RFS) and HG-RFS according to the number of IBCG risk factors harbored by patients and the log-rank test was used for comparisons.
There were 43 patients with 0 risk factors, 113 patients with 1–2 risk factors, and 18 with≥3 risk factors.
After a median follow-up of 36 months, 52 (30%) patients experienced a recurrence. At 3 years, RFS was 86%, 76%, and 54% for patients with 0, 1–2, and≥3 risk factors. At multivariable Cox regression analysis, patients with≥3 risk factors [hazard ratio (HR) 4.76, p=0.002] had a higher risk of any recurrence in reference to patients with 0 risk factors. In contrast, patients with 1–2 risk factors did not show a statistically significant high risk in reference to 0 risk factors (p=0.071).
The 3-yr HG-RFS was 92% for patients with less than 0 risk factors, 94% for patients with 1–2 risk factors, and 76% for patients with≥3 risk factors.
Our results indicated that the presence of≥3 risk factors was associated with a four-fold increase in the risk of any recurrence. Notably, the 3-year RFS rates were 86%, and the HG-RFS rates were 92% for patients with 0 risk factors, whereas the 3-year RFS was 54% and the HG-RFS was 76% for patients with≥3 risk factors. These results showed slightly lower recurrence rates compared to other studies validating the IBCG scoring system and this is probably due to the fact that we selected IR-NMIBC patients potentially eligible for AS (i.e., those with less aggressive cancers).
Moreover, our results support emerging evidence that selected IR-NMIBC patients could be treated with AS, similar to low-risk patients. Repeated TURBTs expose patients, especially the elderly with multiple comorbidities, to general anesthesia risks and post-operative complications like infection, hematuria, and bladder perforation and it becomes increasingly necessary to balance the benefits of surgery with the patient's functional status.
To conclude, patients with LG IR-NMIBC have heterogeneous prognoses based on different prognostic factors. Among those potentially eligible for AS, patients with more than two IBCG risk factors might not be suitable candidates due to a higher risk of subsequent HG recurrence. Randomized controlled trials with standardized AS protocols are needed to validate these findings and optimize patient selection for AS in patients with LG IR-NMIBC.
Written by: Paolo Zaurito, MD, & Pietro Scilipoti, MD
Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.
Read the Abstract