Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies
ABSTRACT Objective The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early‐stage MCC, prompted this study. Methods A systematic review and meta‐analysis of randomized and non‐randomized...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.70553 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841543389714055168 |
|---|---|
| author | Yves Paul Vincent Mbous Rowida Mohamed Usha Sambamoorthi Murtuza Bharmal Khalid M. Kamal Traci LeMasters Joanna Kolodney George A. Kelley |
| author_facet | Yves Paul Vincent Mbous Rowida Mohamed Usha Sambamoorthi Murtuza Bharmal Khalid M. Kamal Traci LeMasters Joanna Kolodney George A. Kelley |
| author_sort | Yves Paul Vincent Mbous |
| collection | DOAJ |
| description | ABSTRACT Objective The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early‐stage MCC, prompted this study. Methods A systematic review and meta‐analysis of randomized and non‐randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease‐specific survival (DSS), and/or disease‐free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model. Results Forty‐nine studies representing 46,215 participants were included in the meta‐analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62–0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I2 = 94%, 95% CI, 93.0–95.5). Both LR (HR = 1.52, 95% CI, 0.37–6.19) and RR (HR = 0.41, 95% CI, 0.09–1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24–1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13–0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E‐value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS. Conclusions Although adjuvant RTx improves survival and recurrence outcomes among early‐stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed. |
| format | Article |
| id | doaj-art-1584bf6db06145f1a243b3e203be0675 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-1584bf6db06145f1a243b3e203be06752025-01-13T13:22:39ZengWileyCancer Medicine2045-76342025-01-01141n/an/a10.1002/cam4.70553Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized StudiesYves Paul Vincent Mbous0Rowida Mohamed1Usha Sambamoorthi2Murtuza Bharmal3Khalid M. Kamal4Traci LeMasters5Joanna Kolodney6George A. Kelley7School of Pharmacy, Department of Pharmaceutical Systems and Policy, Robert C. Byrd Health Sciences Center [North] West Virginia University Morgantown West Virginia USADepartment of Obstetrics and Gynecology, Biological Sciences Division The University of Chicago Chicago Illinois USASchool of Pharmacy, Department of Pharmaceutical Systems and Policy, Robert C. Byrd Health Sciences Center [North] West Virginia University Morgantown West Virginia USAAstraZeneca Oncology Outcomes Research Boston Massachusetts USASchool of Pharmacy, Department of Pharmaceutical Systems and Policy, Robert C. Byrd Health Sciences Center [North] West Virginia University Morgantown West Virginia USAOPEN Health Bethesda Maryland USADepartment of Hematology/Oncology, School of Medicine, Robert C. Byrd Health Sciences Center [North] West Virginia University Morgantown West Virginia USADepartment of Epidemiology and Biostatistics, School of Public Health, Robert C. Byrd Health Sciences Center West Virginia University Morgantown West Virginia USAABSTRACT Objective The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early‐stage MCC, prompted this study. Methods A systematic review and meta‐analysis of randomized and non‐randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease‐specific survival (DSS), and/or disease‐free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model. Results Forty‐nine studies representing 46,215 participants were included in the meta‐analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62–0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I2 = 94%, 95% CI, 93.0–95.5). Both LR (HR = 1.52, 95% CI, 0.37–6.19) and RR (HR = 0.41, 95% CI, 0.09–1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24–1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13–0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E‐value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS. Conclusions Although adjuvant RTx improves survival and recurrence outcomes among early‐stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.https://doi.org/10.1002/cam4.70553disease‐free survivaldisease‐specific survivallocal recurrenceMerkel cell carcinomameta‐analysisoverall survival |
| spellingShingle | Yves Paul Vincent Mbous Rowida Mohamed Usha Sambamoorthi Murtuza Bharmal Khalid M. Kamal Traci LeMasters Joanna Kolodney George A. Kelley Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies Cancer Medicine disease‐free survival disease‐specific survival local recurrence Merkel cell carcinoma meta‐analysis overall survival |
| title | Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies |
| title_full | Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies |
| title_fullStr | Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies |
| title_full_unstemmed | Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies |
| title_short | Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies |
| title_sort | effectiveness and safety of treatments for early stage merkel cell carcinoma a systematic review and meta analysis of randomized and non randomized studies |
| topic | disease‐free survival disease‐specific survival local recurrence Merkel cell carcinoma meta‐analysis overall survival |
| url | https://doi.org/10.1002/cam4.70553 |
| work_keys_str_mv | AT yvespaulvincentmbous effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT rowidamohamed effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT ushasambamoorthi effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT murtuzabharmal effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT khalidmkamal effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT tracilemasters effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT joannakolodney effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies AT georgeakelley effectivenessandsafetyoftreatmentsforearlystagemerkelcellcarcinomaasystematicreviewandmetaanalysisofrandomizedandnonrandomizedstudies |