CHEMOTHERAPY AND BLADDER CANCER
Walter Stadler, MD, FACPUniversity of Chicago
Anatomy as a Problem
One score and seven years ago…
The metastatic d. problem• 1985 - MVAC first reported• 1997 - Gemcitabine first
reported to have activity– GC found comparable to
MVAC in 2000• Response rates:
– 50-55% CR +PR– 10% CR
• OS 14 months− ~5% cured Sternberg et al., J Urol (1985)
Stadler et al., JCO (1997)von der Maase et al., JCO (2000)
For the Patient• Gemcitabine/cisplatin OR MVAC appropriate• Toxicities similar, but potential cardiac problems
and mouth sores with MVAC• Major toxicities of both:
– Low blood counts & risk for infection– Fatigue– Nausea– Neuropathy and hearing loss– Kidney damage
Carboplatin instead of Cisplatin
• More problems with low blood counts• Fewer kidney and neurologic problems• Probably less effective than Cisplatin
– Significance in the metastatic setting debatable
– Should not be used in peri-operative setting
What if Initial Therapy is not Effective
• No standard of care• Responses observed with paclitaxel,
docetaxel, pemetrexed, etc, but not clear how meaningful these are for the patient
• Clinical trial participation preferred
• N=317 pts• Enrolled from 1987 - 1998• Muscle-invasive bladder cancer (stage T2 to T4a, all N0)• Primary objective: compare survival of patients treated
with cystectomy alone vs treated with 3 cycles MVAC followed by cystectomy
• Randomized phase III trial• Median follow-up 8.7 years
(2003)
Overall Survival
Grossman et al., NEJM (2003)
• At five years, 57% alive in combination-therapy group, compared with 43% in cystectomy alone group (P=0.06)
--14% survival difference
Poor Adoption of These Data• Historical rates 5-10%• Retrospective review of patients with bladder
cancer who underwent RC between 2003 and 2008 at University of Texas Southwestern:– Among 238 patients who underwent RC for bladder
cancer, 145 had a preoperative clinical stage ≥T2– Only 17% (25 of 145) received cisplatin-based
neoadjuvant chemotherapy– Renal function was adequate in 97 (67%) of these
patients
Raj et al., Cancer (2011)
Neoadjuvant Chemotherapy
Advantage Disadvantage
Clear Survival Benefit DemonstratedClinical Staging Information Must be Utilized to
Determine Patients to be Treated; Concern for Overtreatment
Patients are More Likely to Receive Intended Chemotherapy than in Post-Operative Setting Patients May be Reluctant to “Delay” Surgery
Does Not Cause Increased Operative Morbidity Non-Responding Patients are Unnecessarily Delaying Definitive Surgical Intervention
Patients are at Their Best Performance Status
Adjuvant Chemotherapy
Advantage DisadvantageFull Pathologic Staging Information Known; Allows
Best Selection of Appropriate Patients for Therapy
Survival Benefit Not Clearly Established
A Small Subset of Patients Ineligible for Cisplatin-Based Neoadjuvant Therapy Due to Poor Renal
Function May Experience Renal Function Improvement Due to Relief of Obstruction from
the Surgery Itself
Patients Less Likely to Receive Intended Chemotherapy Due to Post-Operative Performance Status, Complications
Disadvantage With Adjuvant
Survival Benefit Not Clearly Established
Patients Less Likely to Receive Intended Chemotherapy Due to Post-Operative Performance Status, Complications
Conclusions – Bladder Cancer• Peri-operative CDDP based chemotherapy improves
survival– Best data in neoadjuvant setting– Underutilized
• Ideal utilization rate unknown• >observed 5%; <80%
• Gem/CDDP or MVAC is standard for metastatic disease– Carboplatin based therapies a reasonable option– No good standard for patients in whom initial therapy is not
effective• Current standard is not good enough
– I don’t want to give this talk in 20 yrs again– Clinical trial participation is key