Bladder Cancer Tumor Staging Postchemotherapy Accurately Predicts Survival

Urology Practice Management - December 2015, Vol 4, No 6 - Bladder Cancer
Rosemary Frei, MSc

It is valid to predict survival using tumor stage after neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC), said Peter Black, MD, Senior Research Scientist, Vancouver Prostate Centre, British Columbia, Canada. He presented recent data at the 2015 Congress of the Société Internationale d’Urologie. Their retrospective review showed that a postchemotherapy stage of pT0/Ta/Tis/T1N0 is associated with a significantly longer survival period than a stage of pT≥2N0.

Dr Black noted that this research is laying the groundwork for testing an array of predictive markers to optimize chemotherapy.

“There are a lot of potential markers out there. We’ve already designed a gene signature and tested it in approximately 100 MIBC patients,” Dr Black told Urology Practice Management.

“We found that the signature predicts pathologic response to chemotherapy—that is, pT≥2N0 versus lower stages,” Dr Black said.

He explained that this collaborative work would allow the individualization of chemotherapy for patients.

Dr Black and his team reviewed the records of patients with bladder cancer treated at 17 centers between 2000 and 2013. All patients had undergone neoadjuvant chemotherapy before radical cystectomy for cT2-4aN0M0 bladder cancer. Only patients with pN0 status on final pathology were included.

The neoadjuvant chemotherapy regimens included methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC); gemcitabine and cisplatin; and “other regimens,” comprising carboplatin and gemcitabine, taxanes, and other non–cisplatin-based combinations.

A total of 873 patients were included in the analysis, with a median follow-up of 17 months. A total of 25 patients had pT0N0 stage after neoadjuvant chemotherapy and radical cystectomy, and 207 had stage pTa/Tis/T1N0 disease. The other 409 patients had stage pT≥2N0 disease. The median overall survival was 186.7 months, 138 months, and 84.4 months, respectively.

A Cox regression analysis confirmed that several factors are associated with shorter posttreatment survival, including non-MVAC chemotherapy (for other regimens, the hazard ratio [HR] for decreased survival was 1.91), positive surgical margins (HR, 1.75), and pT≥2 disease (HR, 3.51; all, P <.05).

A second Cox regression analysis had finer-grained divisions between the post–neoadjuvant chemotherapy pathologic stages. This revealed a stepwise increase in HRs: pT1N0 was associated with a 2.28 HR for shorter survival versus lower-stage disease (P = .01); pT2N0 stage had an HR of 2.97, pT3N0 had an HR of 4.43, and pT4N0 had an HR of 5.60 (all, P <.001).

The team then ran 3 additional models—pT0/T1/Tis/T1N0 versus pT≥2N0, pT0/T1/Tis/N0 versus pT≥1N0, and pT pT0/T1/Tis/T1N0 versus pT1N0 and versus pT≥2N0.

The results showed high accuracy, as measured by the area under the receiving operating characteristic curve, with the first model. Furthermore, for this model, the HR for shorter survival was a robust 3.56 (P <.001) for pT≥2N0 versus pT0/T1/Tis/T1N0.

“This is confirmation of what we use in clinical practice, but until now didn’t have good backing—that in the absence of metastatic nodal disease on final pathology, any pathologic down-staging to non–muscle-invasive disease is associated with excellent survival,” concluded Dr Black.

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Last modified: December 29, 2015
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