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Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes
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- Sjödahl, Gottfrid (author)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,Genomiska analyser av urinblåscancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urology - urothelial cancer, Malmö,Lund University Research Groups,Urothelial Cancer Genomics,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital,Lund Univ, Sweden; Skane Univ Hosp, Sweden; Lund Univ, Sweden
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- Abrahamsson, Johan (author)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urology - urothelial cancer, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital,Lund Univ, Sweden; Skane Univ Hosp, Sweden
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- Holmsten, Karin (author)
- Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden; Capio St Goran Hosp, Sweden
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- (creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
- In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 81:5, s. 523-532
- Journal article (peer-reviewed)
Abstract
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- BACKGROUND: For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.OBJECTIVE: To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.DESIGN, SETTING, AND PARTICIPANTS: Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.RESULTS AND LIMITATIONS: Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.CONCLUSIONS: Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.PATIENT SUMMARY: This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Basal/squamous
- Bladder cancer
- Chemotherapy
- Cisplatin
- Luminal
- Molecular subtypes
- Neoadjuvant
- Osteopontin
- Response
- Signature
- SPP1
- Survival
- Urothelial carcinoma
- Bladder cancer; Urothelial carcinoma; Molecular subtypes; Luminal; Basal; squamous; Cisplatin; Chemotherapy; Neoadjuvant; Response; Survival; Osteopontin; SPP1; Signature
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- art (subject category)
- ref (subject category)
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