Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN research group (E2805)

Wenxin Xu; Mäneka Puligandla; Brian Halbert; Naomi B. Haas; Keith T. Flaherty; Robert G. Uzzo; Janice P. Dutcher; Robert S. DiPaola; Venkata Sabbisetti; Rupal S. Bhatt

doi:10.1158/1078-0432.CCR-21-0025

Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN research group (E2805)

Wenxin Xu, Mäneka Puligandla, Brian Halbert, Naomi B. Haas, Keith T. Flaherty, Robert G. Uzzo, Janice P. Dutcher, Robert S. DiPaola, Venkata Sabbisetti, Rupal S. Bhatt

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Purpose: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Experimental Design: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS). Results: Plasma from 418 patients was analyzed. Higher postnephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42-0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (Pinteraction = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56-0.91; P < 0.001). Conclusions: Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.

Original language	English
Pages (from-to)	3397-3403
Number of pages	7
Journal	Clinical Cancer Research
Volume	27
Issue number	12
DOIs	https://doi.org/10.1158/1078-0432.CCR-21-0025
State	Published - Jun 2021

Bibliographical note

Funding Information:
This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer and Mitchell D. Schnall) and supported by the NCI of the NIH under the following award numbers: U10CA180820, U10CA180794, and UG1CA233180. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Funding for biomarker analysis was also provided in part by a Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator Award (to W. Xu). This work was also supported by NIH R01 CA196996 (to R.S. Bhatt), and NIH P50 CA10194212 (to R.S. Bhatt).

Publisher Copyright:
© 2021 American Association for Cancer Research.

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Oncology
Cancer Research

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Xu, W., Puligandla, M., Halbert, B., Haas, N. B., Flaherty, K. T., Uzzo, R. G., Dutcher, J. P., DiPaola, R. S., Sabbisetti, V., & Bhatt, R. S. (2021). Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN research group (E2805). Clinical Cancer Research, 27(12), 3397-3403. https://doi.org/10.1158/1078-0432.CCR-21-0025

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title = "Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN research group (E2805)",

abstract = "Purpose: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Experimental Design: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS). Results: Plasma from 418 patients was analyzed. Higher postnephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42-0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (Pinteraction = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56-0.91; P < 0.001). Conclusions: Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.",

author = "Wenxin Xu and M{\"a}neka Puligandla and Brian Halbert and Haas, {Naomi B.} and Flaherty, {Keith T.} and Uzzo, {Robert G.} and Dutcher, {Janice P.} and DiPaola, {Robert S.} and Venkata Sabbisetti and Bhatt, {Rupal S.}",

note = "Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer and Mitchell D. Schnall) and supported by the NCI of the NIH under the following award numbers: U10CA180820, U10CA180794, and UG1CA233180. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Funding for biomarker analysis was also provided in part by a Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator Award (to W. Xu). This work was also supported by NIH R01 CA196996 (to R.S. Bhatt), and NIH P50 CA10194212 (to R.S. Bhatt). Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",

year = "2021",

month = jun,

doi = "10.1158/1078-0432.CCR-21-0025",

language = "English",

volume = "27",

pages = "3397--3403",

number = "12",

}

Xu, W, Puligandla, M, Halbert, B, Haas, NB, Flaherty, KT, Uzzo, RG, Dutcher, JP, DiPaola, RS, Sabbisetti, V & Bhatt, RS 2021, 'Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN research group (E2805)', Clinical Cancer Research, vol. 27, no. 12, pp. 3397-3403. https://doi.org/10.1158/1078-0432.CCR-21-0025

TY - JOUR

T1 - Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma

T2 - A trial of the ECOG-ACRIN research group (E2805)

AU - Xu, Wenxin

AU - Puligandla, Mäneka

AU - Halbert, Brian

AU - Haas, Naomi B.

AU - Flaherty, Keith T.

AU - Uzzo, Robert G.

AU - Dutcher, Janice P.

AU - DiPaola, Robert S.

AU - Sabbisetti, Venkata

AU - Bhatt, Rupal S.

N1 - Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer and Mitchell D. Schnall) and supported by the NCI of the NIH under the following award numbers: U10CA180820, U10CA180794, and UG1CA233180. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Funding for biomarker analysis was also provided in part by a Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator Award (to W. Xu). This work was also supported by NIH R01 CA196996 (to R.S. Bhatt), and NIH P50 CA10194212 (to R.S. Bhatt). Publisher Copyright: © 2021 American Association for Cancer Research.

PY - 2021/6

Y1 - 2021/6

N2 - Purpose: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Experimental Design: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS). Results: Plasma from 418 patients was analyzed. Higher postnephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42-0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (Pinteraction = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56-0.91; P < 0.001). Conclusions: Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.

AB - Purpose: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Experimental Design: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS). Results: Plasma from 418 patients was analyzed. Higher postnephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42-0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (Pinteraction = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56-0.91; P < 0.001). Conclusions: Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.

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Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN research group (E2805)

Abstract

Bibliographical note

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UN SDGs

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