Research Article: Multiple recurrences and risk of disease progression in patients with primary low-grade (TaG1) non–muscle-invasive bladder cancer and with low and intermediate EORTC-risk score

Date Published: February 27, 2019

Publisher: Public Library of Science

Author(s): Marie Simon, Pierre-Olivier Bosset, Mathieu Rouanne, Simone Benhamou, Camelia Radulescu, Vincent Molinié, Yann Neuzillet, Xavier Paoletti, Thierry Lebret, Francisco X. Real.

http://doi.org/10.1371/journal.pone.0211721

Abstract

To assess the prognostic value of multiple recurrences on the risk of progression in a large cohort of TaG1 bladder cancer of low and intermediate risk based on the EORTC score and to evaluate prognostic factors of multiple recurrences.

We retrospectively analyzed a French cohort of 470 patients with primary TaG1 bladder cancer diagnosed between 1986 and 2010 and followed until 2012. They were classified at low and intermediate risk using the EORTC risk score. Associations between the number of recurrences and the risk of progression to high grade Ta/T1 bladder cancer and progression to muscle-invasive disease were assessed. The characteristics of recurrences, as occurrence time or localization, and risk of other recurrences were evaluated.

Out of 470 patients, 251 had recurrence, 34 progressed to high grade Ta/T1 and 17 to muscle-invasive disease, including 4 who had non muscle-invasive progression first. The median follow-up was 7.2 years (interquartile range: 4.2–10.9). In half the progressions, no previous recurrence was observed. No association between the number of recurrences and the risk of progression was detected. Even after 5 years free of event, patients had a 15% risk of recurrence. History of two or more recurrences increased by 4.5 the risk of subsequent recurrence. Time between two recurrences inferior to six months and multifocal localization increased the risk of recurrence.

Surveillance of patients with TaG1 should be continued beyond 5 years of follow-up. However, cystoscopy exams could be spaced after 5 years. Multiple TaG1 recurrences did not appear to be prognostic for disease progression, but increased significantly the risk of subsequent recurrences. Short time between two recurrences and multifocal localization may serve to adapt monitoring of patients with TaG1 Bladder cancer.

Partial Text

Bladder cancer (BC) is the 9th most commonly diagnosed cancer in the world [1]. The worldwide age standardized incidence rate (per 100,000 person-years) was 9.0 for men and 2.2 for women in 2012 [1]. In France, the incidence is increasing by about 1% per year [2–3]. Approximately 75–85% of BC are non-muscle-invasive. Of these, 70% are stage Ta, 20% are T1 and 10% are in situ (Cis) [4–7]. Ta papillary tumors with histopathological grade (G) 1 (or low grade) are those most frequently found at diagnosis. The natural history of superficial bladder cancer is characterized by a high rate of recurrence (between 30% and 78% at 5 years) in the same stage/grade but a limited five-year risk of progression to muscle invasive disease of stages T2 to T4 (7% to 40%) [8–11]. These recurrent events alter the patient’s quality of life and might increase the risks of progression either to a High-grade Ta, T1, CIS, or to T2-T4 pathological stage, which in turns have a major impact on the therapeutic management.

In this large single-center cohort of 470 primary TaG1 low and intermediate risk BC with long-term follow-up, we found that half of the patients with disease progression did not experience any prior tumor recurrence resulting in the absence of association between the two outcomes, even for patients with multiple (>4) recurrences. However, history of 2 or more recurrences increased by 4.5 the risk of subsequent recurrence. Even 5 years free of recurrence after the initial TURB, patients had a 15% risk of developing a new recurrence, suggesting that follow-up should be maintained on a long-term period. Indeed, we also found that previous recurrence within the last 6 months was prognostic of new recurrence. Finally, we confirmed that multifocal localization at diagnosis was a risk factor of subsequent recurrence [7–13].

The number of low-grade (TaG1) recurrences did not appear to be prognostic for disease progression, but increased significantly the risk of subsequent recurrences as a short time to recurrence and multifocal localization did. Therefore, surveillance of patients with TaG1 tumors at low / intermediate risk based on the EORTC score might be adapted based on those simple variables. It should be continued beyond 5 years of follow-up as 17 of the 47 progressions occurred 5 years after initial TURB and the hazard of any progressions remained relatively high but yearly cystoscopy could be recommended instead of 6-monthly exams to account for the decreasing risk of recurrence.

 

Source:

http://doi.org/10.1371/journal.pone.0211721

 

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