Analyzing urine samples for minimal residual disease (MRD) could help guide treatment in patients with bladder cancer, according to research published in PLOS Medicine.

Researchers found that MRD positivity was significantly associated with pathologic complete response (pCR) and progression-free survival (PFS).

For this study, the researchers used next-generation sequencing to detect urine tumor DNA (utDNA) in urine cell-free DNA samples.


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The team analyzed samples from 42 patients with localized bladder cancer — collected just before the patients underwent radical cystectomy — as well as samples from 15 healthy control individuals.

Of the 42 bladder cancer patients, 32 had muscle-invasive bladder cancer (MIBC), and 19 of the MIBC patients received neoadjuvant chemotherapy.

The researchers found that 16 patients (38%) achieved a pCR, and 26 (62%) did not. The median utDNA level was significantly higher in patients without a pCR (4.3%) than in those with a pCR (0%; P =.002) or in healthy control individuals (0%; P <.001).

Patients without a pCR had significantly more mutations than patients with a pCR — a median of 2 mutations and 0 mutations per patient, respectively. TERT and TP53 were the most commonly mutated genes.

The researchers also found that 81% of patients without a pCR were utDNA MRD-positive. MRD positivity was significantly associated with a lack of pCR (P <.001), with a sensitivity and specificity of 81%.

MRD-positive patients had significantly worse PFS compared with MRD-negative patients (hazard ratio, 7.4; 95% CI, 1.4-38.9; P =.02).

The researchers also attempted to infer tumor mutational burden (TMB) in the bladder cancer cohort by leveraging data from 409 MIBC tumors in The Cancer Genome Atlas. The results suggested that 58% of utDNA MRD-positive patients with high TMB inferred from urine might have been candidates for adjuvant immunotherapy.

“utDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment,” the researchers wrote. “utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer patients in the future.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Chauhan PS, Chen K, Babbra RK, et al. Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study. PLoS Med. 2021;18(8):e1003732. doi:10.1371/journal.pmed.1003732