Study links early recurrence, bladder cancer progression

In patients with primary T1G3 bladder cancer who undergo initial treatment with endovesical bacillus Calmette-Guerin (BCG [TheraCys, TICE BCG]), development of high-grade disease recurrence after 3 months is a prognostic factor for progression.

"About 10% of patients with non-muscle-invasive bladder cancer present with T1G3 disease," said co-author Joan Palou, MD, chief of urologic oncology and associate professor of urology, Fundacio Puigvert, Barcelona, Spain. "Although radical cystectomy would result in overtreatment of significant numbers of patients, a significant number of patients will progress to develop muscle-invasive disease after conservative primary immunotherapy. The challenge to clinicians is to identify patients at risk for progression so that they can intervene surgically while the prognosis is still favorable.

"In previous studies trying to define risk factors for progression to muscle-invasive disease after treatment with BCG, recurrence after 3 months has been reported as a predictor, but others report first recurrence at 6 months. Our study shows that it is earlier recurrence that is important, but also that the grade of recurrence defines the at-risk group."

The study analyzed recurrence and progression rates for a cohort of 146 patients with primary T1G3 bladder cancer. The study population was comprised of almost 90% men, and carcinoma in situ was present in about two-thirds of the cohort. All patients had undergone transurethral resection and multiple bladder biopsies followed by an induction course (once weekly for 6 weeks) of endovesical BCG.

Patients were monitored with cystoscopy and cytology at quarterly intervals for the first 2 years after BCG treatment and then semi-annually. Follow-up for the group ranged from 4 to 176 months with a median of 94 months.

Cancer recurrence, defined as reappearance of non-muscle-invasive disease, was noted in 51 patients (34.9%); of these tumors, 16 were low-grade and 35 were high-grade tumors. Progression was defined as appearance of muscle-invasive disease (pT2 or higher), and it occurred in only one (6.25%) of 16 patients who had a low-grade recurrence, but in seven (20%) of the 35 patients with a high-grade recurrence.

Among the patients with a high-grade recurrence, the recurrence was identified at 3 months in eight patients and at 6 months or later in 27. The progression rate in the patients who developed a high-grade recurrence at 3 months was 50% and was significantly higher than the 11.1% progression rate in the patients whose high-grade recurrence occurred later.

"We believe early high-grade recurrence is probably persistence of disease that was not responsive to BCG, and these patients should be considered for radical cystectomy," Dr. Palou told Urology Times. "However, if the early recurrence is a low-grade tumor, treating the patient again conservatively with BCG seems to be a reasonable option that would not put the patient at risk for a poor outcome."