San Diego, CA USA (UroToday.com) In today’s Society of Urologic Oncology meeting at the AUA, Dr. Sam Chang discussed the selection of T1 patients for initial cystectomy. He began by discussing general factors that impact outcomes for T1 cancer, including patient-related, tumor-related, surgeon-related, and pathologist-related variables.
Quality TURBT is paramount to optimal risk stratification of patients. When muscle is not present or not mentioned in the path report, there is more than a doubling of patients who die of disease compared to those patients in whom muscle is present at TURBT. Re-TURBT for T1 tumors has become more consistently performed, and should be performed if planning bladder conservation. It is associated with improved response rate to BCG, reduces recurrences and under-staging by 20-40%, delays time and decreases rate of progression, and can be predictive of outcomes. Re-TURBT does not, however, guarantee safety: 47% of patients in Vanderbilt’s series were still understaged at the time of cystectomy.
High grade T1 can be considered dangerous, as it is associated with 39% recurrence rate and 20% progression rate at 5 years. Allelic analyses have shown closer relationship between T1 and T2-T4 disease than between T1 and Ta. Molecular markers such as Ki67, P27, and P53 may help predict who has more aggressive disease within T1 tumors.
Cystectomy is curative, with 92% OS and 83% RFS for T1 disease at 5 years, and survival is better when cystectomy is performed early rather than late (90% 5 year survival if performed within 3 months of diagnosis vs 50% if delayed). EORTC predictors of progression include stage, focality, CIS, primary vs recurrent disease, size, and grade. Within T1 disease, important prognostic factors include presence of T1 at re-TUR, T1 substaging, LVI, and histologic variants.
Regarding substaging, rates of progression increase with depth of penetration: progression rates are 6%, 33%, and 55% for T1a, T1b, and T1c disease, respectively. Martin-Doyle and colleagues found that depth of T1 disease is the strongest predictive factor of survival and progression. Studies that examined the impact of extent of invasion have found a difference between microinvasive vs extensive invasive disease; a 1.5mm depth cutoff was first described with Cheng and colleagues (JCO 1999), and more recent data suggests that a 1mm cutoff is associated with increased risk of progression. LVI similarly can be prognostic of outcomes, including recurrence (HR =2.19) and stage progression (HR =3.76; Fukomoto et al, BMC Urol 2016). LVI is important even after cystectomy for pT1 N0 disease, as RFS is worse in LVI+ patients.
LVI and T1 substaging may be difficult though as pathologic issues abound. These include poor orientation due to tangential sectioning, thermal injury, inflammatory response, nested variants mimicking Von Brunn’s nests, and confusion between a prominent muscularis mucosa and muscularis propria.
Dr. Chang concluded that, ultimately, timely cystectomy should be offered to select patients. Absolute requirements are operative candidates and those with endoscopically unresectable tumors. Patients who should undergo cystectomy are those with histologic variants. Those with multiple risk factors, including LVI, deep invasion, CIS, and heavy disease burden should be encouraged to undergo timely cystectomy.
Presented By: Sam Chang , MD
Written By: Dr. Nikhil Waingankar, MD; Fox Chase Cancer Center, Philadelphia, PA at the 2016 AUA Annual Meeting - May 6 - 10, 2016 – San Diego, California, USA
Follow on Twitter: @nwaingankar