'Very-Low-Risk' Bladder Cancer Described

Kristin Jenkins

January 03, 2018

About 40% of patients with low-risk bladder cancer can be put into a "very-low-risk" category characterized by younger patient age, smaller tumors, and a lower recurrence rate than patients with larger tumors, according to researchers.

Analysis of data from a series of 211 low-risk bladder cancer cases shows that in patients with tumors with a diameter of 1 cm or less, most recurrences took place after the recommended 5-year surveillance period and can thus be described as very low risk, say Ofer N. Gofrit, MD, PhD, from the Department of Urology at Hadassah Hebrew University Hospital, Jerusalem, Israel, and colleagues.

Their report was published on December 23, 2017, in BJU International (formerly the British Journal of Urology).

The median time to recurrence was 5.7 years in patients with tumors 1 cm or less compared with 3.6 years in patients with tumors 1.1 to 3.0 cm in diameter (P = .003), highlighting the need for longer follow-up in patients with smaller tumors, the study authors emphasize.

At present, patients diagnosed with low-risk non–muscle-invasive urothelial carcinomas have primary, solitary, low-grade tumors smaller than 3 cm with no evidence of carcinoma in situ, the investigators note. The 5-year risk for progression for these low-risk tumors is 0.8%.

"Taken together, it seems that these patients [with tumors ≤1 cm] can be classified separately to a 'very-low-risk' group," the study authors suggest. Cystoscopy at 3 months after resection followed by annual ultrasound evaluation for 10 years "is a reasonable surveillance protocol," they add.

Notably, only 43.7% of recurrences happened within the first 5 years in patients with tumors 1 cm or less. More than half of recurrences in this group were spread out over the remaining 10-year period. By comparison, 75.5% of recurrences in patients with larger tumors took place in the first 5 years after surgery.

Patients with smaller tumors were also significantly younger than those with larger tumors (64.6 vs 68.3 years; P = .03) and were more likely to be asymptomatic at presentation (P = .047). They had a 5-year recurrence-free survival rate of 92%, compared with 70% in those with larger tumors (P = .0009).

Recurrence in this "very-low-risk" subgroup probably represents a new event of carcinogenesis, Dr Gofrit and colleagues say.

Patients with larger, low-risk tumors "can be termed 'new-low-risk' or just 'low-risk' exactly as in prostate cancer," they suggest. For this group, "the current guidelines seem very appropriate."

Asked to comment, Alexander Kutikov, MD, chief of the Division of Urologic Oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania, said there is "compelling established evidence that once a bladder tumor develops, recurrence risks exist indefinitely."

After a diagnosis of bladder cancer, "most urologic oncologists monitor young patients long term, regardless of primary tumor size," he told Medscape Medical News. "These data support this practice, since a nontrivial number of patients exhibit recurrence and grade/stage progression."

Dr Kutikov, who was not affiliated with the study, also noted that guideline panels "struggle to balance the persistent risks of recurrence against the burden of indefinite surveillance and its costs."

Looking ahead, he predicted that genomic risk stratification in bladder cancer will change the way clinicians approach surveillance. "This space remains ripe for disruption with improved risk stratification," he said.

For now, however, Dr Kutikov emphasized that "cystoscopic evaluation and upper tract imaging is the standard of care surveillance strategy for patients with urothelial carcinoma."

Study Details

In the analysis, the study authors mined a database of 43 women and 168 men who had undergone transurethral resection for low-risk bladder cancer between June 1998 and December 2008. Mean age of the study cohort was 66.7 years, and all patients were followed for a median of 10 years.

Recurrence was diagnosed in 65 patients (30.7%) after a median of 3.15 years. The recurrence rate was significantly higher in female patients (P = .039) and in patients with tumors larger than 1 cm (P = .012).

Stage progression was seen in 1.4% of patients, all of whom had primary tumors larger than 1 cm. Grade progression was seen in 2.4%, but there were no cases of disease-specific mortality.

Postoperative follow-up included cystoscopy at 3 and 12 months and then annually for 5 years. After this, patients underwent a yearly ultrasound exam of the urinary system indefinitely.

This approach is in keeping with the philosophy "that the risk of bladder cancer recurrence never drops to zero," the study authors say. This policy is also what created the long-term database for the study.

Guidelines issued by the Canadian Urological Association in 2010 recommend cystoscopic examination 3 and 9 months after surgery and "annually thereafter," Dr Gofrit and colleagues point out. However, other guidelines recommend follow-up after primary resection of a low-risk tumor with periodic cystoscopy for up to 60 months.

Guidelines issued by the American Urological Association/ Society of Urologic Oncology, the National Comprehensive Cancer Network, and the European Association of Urology are based on studies with a median follow-up of 3.9 years that "miss the late recurrences typical of 'very-low-risk' patients," the study authors say.

In the United Kingdom, the National Institute for Health Care and Excellence recommends follow-up cystoscopy at 3 and 12 months after diagnosis before discharge to primary care. These guidelines also ignore the risk for late recurrence, the researchers note.

In the absence of additional follow-up, "this policy would miss 75% of the recurrences in the current series, which comprises 23% of all patients with 'low-risk' bladder cancer," they say.

Dr Gofrit and study coauthors have disclosed no relevant financial relationships. Dr Kutikov disclosed financial relationships with Visible Health, Genomic Health, and Novartis.

BJU Int. Published online December 23, 2017. Abstract

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