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Therapeutic responses to chemotherapy or immunotherapy by molecular subtype in bladder cancer patients: A
Shunde Wang1, Xiaoyu Yuan2, Zhongjie Shen2
1Department of Urology, The ChenJiaqiao Hospital of ShaPingba District of Chongqing City, Chongqing, China.
Abstract:
To systematically evaluate the differences in therapeutic response to chemotherapy or immunotherapy between different molecular subtypes of bladder cancer (BC). A comprehensive literature search was performed up to December 2021. Consensus clusters 1 (CC1), CC2 and CC3 molecular subtypes were used to perform meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the therapeutic response by fix-effect modeling. Eight studies involving 1,463 patients were included. For immunotherapy, CC3 showed the highest response rate (CC1 vs. CC3: OR=0.52, 95% CI=0.34-0.78, p=0.002; CC2 vs. CC3: OR=0.42, 95% CI=0.28-0.62, p<0.001), which was mainly reflected in the highest response rate to atezolizumab (CC1 vs. CC3: OR=0.47, 95% CI=0.29-0.75, p=0.002; CC2 vs. CC3: OR=0.38, 95% CI=0.24-0.59, p<0.001). For chemotherapy, CC3 had the lowest response rate to the overall chemotherapy (CC1 vs. CC3: OR=2.05, 95% CI=1.23-3.41, p=0.006; CC2 vs. CC3: OR=2.48, 95% CI=1.50-4.10, p<0.001). Compared with CC2, CC3 responded poorly to both neo-adjuvant chemotherapy (NAC) (OR=1.93, 95% CI=1.09-3.41, p=0.020) and chemoradiation therapy (CRT) (OR=6.07, 95% CI=1.87-19.71, p<0.001). Compared with CC1, CC3 only showed a poorer response to CRT (OR=4.53, 95% CI=1.26-16.27, p=0.020), and no difference in NAC. Our study suggested that molecular classifications are important predictors of cancer treatment outcomes of BC patients and could identify subgroup patients who are most likely to benefit from specific cancer treatments.
Insights
Bladder cancer molecular subtypes significantly impact treatment response. CC3 subtypes show higher immunotherapy response but lower chemotherapy response, guiding personalized treatment strategies.
Area of Science:
- Oncology
- Translational Research
- Cancer Genomics
Background:
- Bladder cancer (BC) exhibits diverse molecular subtypes.
- Understanding subtype-specific treatment responses is crucial for optimizing patient outcomes.
Purpose of the Study:
- To systematically evaluate therapeutic response differences to chemotherapy and immunotherapy across distinct molecular subtypes of bladder cancer.
- To identify which molecular subtypes benefit most from specific treatments.
Main Methods:
- A meta-analysis was conducted on eight studies involving 1,463 patients, up to December 2021.
- Consensus clusters 1 (CC1), CC2, and CC3 molecular subtypes were analyzed.
- Pooled odds ratios (ORs) with 95% confidence intervals (CIs) assessed treatment response using fixed-effect modeling.
Main Results:
- Molecular subtype CC3 demonstrated the highest response rate to immunotherapy, including atezolizumab, compared to CC1 and CC2.
- Conversely, CC3 exhibited the lowest response rate to overall chemotherapy, neo-adjuvant chemotherapy (NAC), and chemoradiation therapy (CRT).
- CC3 showed poorer responses to NAC and CRT compared to CC2, and poorer response to CRT compared to CC1.
Conclusions:
- Molecular classification is a key predictor of bladder cancer treatment outcomes.
- Identifying specific molecular subtypes can guide the selection of optimal cancer therapies for individual patients.
- This research supports personalized treatment approaches based on bladder cancer molecular subtypes.
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