|The following article features coverage from the 2019 Genitourinary Cancers Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Adjuvant chemotherapy added to postoperative radiation therapy (PORT) improves outcomes for patients following radical cystectomy (RC) for locally advanced urothelial (UC) carcinoma of the bladder, according to study findings presented at the 2019 Genitourinary Cancers Symposium.
Compared with PORT alone, PORT plus sequential adjuvant chemotherapy prolonged disease-free survival (DFS) and overall survival (OS) in a study of 81 patients with locally advanced UC of the bladder, according to Brian C. Baumann, MD, who presented the findings.
The 81 patients were among a group of 153 patients with locally advanced bladder cancer enrolled in a randomized phase 3 trial (ClinicalTrials.gov Identifier: NCT01734798) comparing PORT alone with sequential chemotherapy plus PORT. Eligibility criteria for the study, which was led by Mohamed S. Zaghloul, MD, of the Egyptian National Cancer Institute in Cairo, included pT3b disease or higher, grade 3 cancer, or positive lymph nodes, as well as negative surgical margins after RC plus pelvic node dissection.
Of the 81 patients with UC, 40 received PORT alone and 41 received chemotherapy plus PORT. PORT consisted of 3D conformal radiation therapy to the pelvis up to a dose of 45 Gy given in 1.5 Gy fractions twice daily. Chemotherapy recipients received 2 cycles of gemcitabine and cisplatin before and after radiation therapy. Patients received follow up every 2 months for the first 2 years and then every 6 months thereafter. Computed tomography scans were performed every 6 months for the first 2 years and then annually thereafter.
The median age of patients in the combined modality arm and PORT-only arm was 54 and 55 years, respectively. The median follow-up time was 21 months for the chemotherapy-PORT group and 15 months for the PORT-only group.
Two-year DFS rates for the chemotherapy-PORT and PORT-only arms were 62% (95% CI, 53%-71%) and 48% (95% CI, 39%-58%), respectively. Two-year OS rates were 71% (95% CI, 63%-80%) and 51% (95% CI, 40%-61%), respectively. On multivariable analysis, the chemotherapy-PORT group had a significant 58% decreased risk of disease progression (hazard ratio [HR], 0.42; 95% CI, 0.21-0.85; P =.016) and 55% decreased risk of death (HR, 0.45; 95% CI, 0.21-0.96; P =.039) compared with the PORT-only group.
In the entire cohort, late grade 3 or higher gastrointestinal toxicity occurred in 5 patients in the PORT plus chemotherapy group (7%) and 6 patients in the PORT-only arm (8%).
“These results, I think, strongly suggest a role for adjuvant therapies to address both the local and distant disease in patients with locally advanced bladder cancer,” Dr Baumann stated during the presentation.
The improvement in disease-free and overall survival with adjuvant chemotherapy in this relatively small cohort is “somewhat surprising,” he said, adding that previous larger trials failed to find such a benefit.
Dr Baumann believes adjuvant radiation is shifting the pattern of failure toward more distant-only relapse, “which could be more effectively treated with chemo[therapy].” The prior adjuvant chemotherapy trials, he explained, did not include adjuvant local therapy to address the problem of local failure. Therefore, the DFS benefit in those trials may have been limited to patients who were otherwise destined for distant-only relapse.
“Our hypothesis is that the use of adjuvant radiation, which significantly improves local control, has a synergistic effect with chemo[therapy], improving the effectiveness of chemo[therapy] to prevent disease recurrence.”
Read more of Cancer Therapy Advisor‘s coverage of the 2019 Genitourinary Cancers Symposium by visiting the conference page.
- Zaghloul MS, Christodouleas JP, Hwang WT, et al. Randomized phase III trial of adjuvant sequential chemotherapy plus radiotherapy versus adjuvant radiotherapy alone for locally advanced bladder cancer after radical cystectomy: Urothelial carcinoma subgroup analysis. Data presented at: 2019 Genitourinary Cancers Symposium; San Francisco, CA; February 14-16. Abstract 351.