Tuesday, June 26, 2012

Outcomes of pT0N0 at radical cystectomy: The Canadian Bladder Cancer Network experience

Imported data are updated from this paper

In 2012, there will be an estimated 73,510 people diagnosed  with bladder cancer and approximately 14,880 deaths due to this disease.”
Bladder cancer is the fourth most common cancer in men and eighth most common in women.
While most patients presenting with bladder cancer have superficial disease (<cT2), about 25% of these individuals will have at least muscle invasive (≥cT2) or node positive (N+) disease.
Currently, radical cystectomy (RC) is the standard of care for the management of organ-confined muscle invasive or high-risk superficial disease.
About 10% of patients (range: 5-20) will have no evidence of tumour at pathological examination of the cystectomy specimen; such patients are designated stage pT0.
The clinical outcomes and significance of patients with stage pT0 disease at cystectomy is unclear. Thrasher and colleagues reviewed survival outcomes in these patients and found that survival in this population was determined by the presenting clinical stage. However, Palapattu and colleagues found that survival in patients with pT0 is similar to those with pTa and pTis (in situ) and Cho and colleagues found survival to be similar to those with pTis and T1 disease. In an effort to help clarify the clinical significance of  patients with stage pT0N0 disease at cystectomy, we assessed clinical outcomes of these patients following RC using a contemporary series of bladder cancer patients treated by urologic oncologists from multiple Canadian academic centres. 

Cystectomy specimens were processed and evaluated by staff pathologists with genitourinary expertise. Pathologic staging was in accordance with the 1997 TNM classification.
Postoperative surveillance consisted of routine history and physical examination, blood chemistry analysis, abdominal/pelvic imaging, urinary cytology and chest x-ray. All assessments were repeated every three to six months for the first five years and at increasing intervals thereafter. Any additional evaluation was done on an individual basis at the discretion of the treating physician.
Measured survival outcomes included recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS). Time to recurrence was calculated as the time interval from surgery to evidence of clinical recurrence or last follow-up in the absence of any recurrence. Time to DSS was determined as the time interval from surgery to the date of death from bladder cancer or last follow-up if the patients had not died of bladder cancer. Time to OS was assessed as the time from surgery to the date of death, regardless of cause of death.
Patient and clinical characteristics
The entire study cohort consisted of 2287 patients, of which 135 (5.9%) patients had pT0N0 disease and 25 (1.1%) patients had pT0N+ disease. No patients with pT0 had metastatic disease. Of the 135 patients with pT0N0, TCC was the primary histology in 68.9% (83), and 80% (108) were male. Median age was 66 years (range: 39-72) and median follow-up of living patients was 42 months (range: 3-180). Most patients had either clinical T1 or T2 stage disease (65.9% of 135 patients). There was a history of concomitant CIS in 24% and a history of previous superficial TCC in 35% of patients. Very few patients did not receive a lymph node dissection (7.4%). Neoadjuvant chemotherapy was offered to 11 (8.1%) of 135 patients with pT0N0, and 71 (3.1%) patients in the entire study cohort. Adjuvant chemotherapy was not offered to any patients in the pT0N0 group.
Clinical outcomes with pT0N0 pathology
The five- and 10-year RFS for pT0N0 was 83% and 66%, respectively; moreover, the five- and 10-year DSS for pT0N0 was 96% and 92%, respectively. The five- and 10-year OS was 88% and 70%, respectively. The five-year RFS, DSS and OS for the entire study population (2287) were 57%, 48% and 67%, respectively.
The frequency of pT0 pathology at RC has been reported to range from 5% to 20%.
The frequency of 5.9% of pT0 disease from the Canadian Bladder Cancer Network is in keeping with the published range.
There are a number of causes of a pT0 RC specimen, including effective neoadjuvant therapy, complete endoscopic resection prior to cystectomy, residual tumour that is too small to be detected, and misdiagnosis at TURBT.

The results of this large multicentre study suggest that patients with pT0N0 have excellent outcomes from cystectomy with high five- and 10-year RFS, DSS and OS; however, there still remains a risk of tumour recurrence in this patient population. Given that patients with pT0N0 pathology are a heterogeneous group, ongoing postoperative surveillance is required for these patients.



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