Tumor-adjacent B cell infiltration stratifies recurrence risk in localized prostate cancer
- 1Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA
Abstract
BackgroundBiochemical recurrence (BCR) occurs in 20-40% of men after radical prostatectomy. Existing postoperative recurrence risk tools based on PSA and pathology are clinically useful but show only moderate and variable discrimination, highlighting the need for biomarkers that improve risk stratification and consequent treatment decisions. We hypothesized that the prostate microenvironment, including both the tumor and non-cancerous adjacent tissue, may contain prognostic features associated with adverse postoperative PSA outcomes.
MethodsWe assembled a cohort of matched tumor-adjacent benign and tumor prostate tissue from 243 men across three institutions to establish a discovery cohort (n=123; 43 postoperative PSA events, 35%) and validation cohort (n=120; 46 events, 38%). For primary binary analyses, a postoperative PSA event included BCR, defined as two consecutive postoperative PSA values [≥]0.2 ng/mL, or PSA persistence. We performed RNA sequencing of matched tumor-adjacent benign and tumor tissues, quantified immune signatures, and developed an integrated model combining the adjacent-tissue B-cell signature, preoperative PSA, and radical prostatectomy Gleason score ("BRIGADE"). CAPRA-S-adjusted Cox analyses excluding recurrence-time-0 cases evaluated time to BCR, and CD19 multiplex immunofluorescence provided tissue-level confirmation (n=10).
ResultsIn prostatectomy specimens, tumors from patients without a postoperative PSA event were enriched for B-cell transcriptional programs, whereas tumors from event-positive patients showed elevated proliferation signatures. B-cell-related transcriptional programs were correlated between tumor and adjacent tissue. Tumor-adjacent benign B-cell scores were higher in no-event cases and discriminated postoperative PSA-event status in PCBN discovery (AUC 0.63) and BM validation (AUC 0.81) cohorts, outperforming numerous other immune-related signatures. In CAPRA-S-adjusted Cox sensitivity analyses excluding recurrence-time-0 cases, higher adjacent-tissue B-cell activity was associated with reduced recurrence risk in PCBN (HR 0.42, 95% CI 0.19-0.94; BH-adjusted p=0.035) and BM (HR 0.54, 95% CI 0.30-0.95; BH-adjusted p=0.034). Tissue-based validation showed that CD19 B-cell density in adjacent benign tissue was higher in no-event than event-positive patients (median 0.1145 vs 0.0471; p=0.008). BRIGADE achieved an AUC of 0.68 in cross-validation and 0.83 in independent validation, compared to AUCs of 0.54-0.63 and 0.44-0.78 for the tested clinical predictors, respectively. At the fixed classification threshold, the validation-cohort odds ratio for BRIGADE was 2.75. The adjacent B-cell score remained associated with lower odds of a postoperative PSA event after adjustment for PSA and Gleason score.
ConclusionsB-cell infiltration in tumor-adjacent benign prostate tissue may complement existing clinicopathologic models for stratifying adverse postoperative PSA outcomes and subsequent BCR after radical prostatectomy. The transcriptomic signal was recapitulated by CD19-based tissue staining, supporting further development of a pathology-based assay.
Related
- Salvage High-Dose-Rate Brachytherapy for Localized Prostate Cancer Recurrence: A Comparative Analysis of 2 Fractionation Schedules-Single-Institution Study of 223 Patients.
- Prognostic value of postoperative dynamic PNI trajectories for biochemical recurrence in patients with high-risk localized prostate cancer: a longitudinal trajectory clustering study.
- A combined carbohydrate antigen 125 and lymphocyte-to-monocyte ratio score stratifies time-window-specific recurrence after pancreatic cancer surgery.
- Preoperative thymic output and T cell repertoire diversity are associated with recurrence after nephrectomy for localized renal cell carcinoma
- Perioperative apalutamide in high-risk localized or locally advanced prostate cancer: Is PROTEUS trial practice changing?
BibTeX
@misc{wang2026tumoradjacent,
title = {{Tumor-adjacent B cell infiltration stratifies recurrence risk in localized prostate cancer}},
author = {B. Wang and S. Mukherjee and A. Baj and S. Y. Trostel and R. T. Lis and N. C. Whitlock and A. T. Ku and K. E. Heyward and S. Kartal and K. Wang and O. S. Voznesensky and C. Calagua and J. Siddiqui and R. S. Martin and L. A. Kollath and J. Custer and P. D. Michael and L. P. Kunju and R. Lake and C. C. Harris and K. D. Aldape and L. D. True and C. Tatsuoka and E. J. Fertig and A. Chinnaiyan and S. Gurram and P. A. Pinto and A. B. Weiner and C. Morrissey and S. S. Salami and D. J. Einstein and S. P. Balk and A. G. Sowalsky and E. Ruppin},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.26361718},
url = {https://www.medrxiv.org/content/10.64898/2026.08.29.26361718v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Tumor-adjacent B cell infiltration stratifies recurrence risk in localized prostate cancer
AU - B. Wang
AU - S. Mukherjee
AU - A. Baj
AU - S. Y. Trostel
AU - R. T. Lis
AU - N. C. Whitlock
AU - A. T. Ku
AU - K. E. Heyward
AU - S. Kartal
AU - K. Wang
AU - O. S. Voznesensky
AU - C. Calagua
AU - J. Siddiqui
AU - R. S. Martin
AU - L. A. Kollath
AU - J. Custer
AU - P. D. Michael
AU - L. P. Kunju
AU - R. Lake
AU - C. C. Harris
AU - K. D. Aldape
AU - L. D. True
AU - C. Tatsuoka
AU - E. J. Fertig
AU - A. Chinnaiyan
AU - S. Gurram
AU - P. A. Pinto
AU - A. B. Weiner
AU - C. Morrissey
AU - S. S. Salami
AU - D. J. Einstein
AU - S. P. Balk
AU - A. G. Sowalsky
AU - E. Ruppin
PY - 2026
DA - 2026/08/29
PB - medRxiv
DO - 10.64898/2026.08.29.26361718
UR - https://www.medrxiv.org/content/10.64898/2026.08.29.26361718v1
AB - BackgroundBiochemical recurrence (BCR) occurs in 20-40% of men after radical prostatectomy. Existing postoperative recurrence risk tools based on PSA and pathology are clinically useful but show only moderate and variable discrimination, highlighting the need for biomarkers that improve risk stratification and consequent treatment decisions. We hypothesized that the prostate microenvironment, including both the tumor and non-cancerous adjacent tissue, may contain prognostic features associated with adverse postoperative PSA outcomes. MethodsWe assembled a cohort of matched tumor-adjacent benign and tumor prostate tissue from 243 men across three institutions to establish a discovery cohort (n=123; 43 postoperative PSA events, 35%) and validation cohort (n=120; 46 events, 38%). For primary binary analyses, a postoperative PSA event included BCR, defined as two consecutive postoperative PSA values [≥]0.2 ng/mL, or PSA persistence. We performed RNA sequencing of matched tumor-adjacent benign and tumor tissues, quantified immune signatures, and developed an integrated model combining the adjacent-tissue B-cell signature, preoperative PSA, and radical prostatectomy Gleason score ("BRIGADE"). CAPRA-S-adjusted Cox analyses excluding recurrence-time-0 cases evaluated time to BCR, and CD19 multiplex immunofluorescence provided tissue-level confirmation (n=10). ResultsIn prostatectomy specimens, tumors from patients without a postoperative PSA event were enriched for B-cell transcriptional programs, whereas tumors from event-positive patients showed elevated proliferation signatures. B-cell-related transcriptional programs were correlated between tumor and adjacent tissue. Tumor-adjacent benign B-cell scores were higher in no-event cases and discriminated postoperative PSA-event status in PCBN discovery (AUC 0.63) and BM validation (AUC 0.81) cohorts, outperforming numerous other immune-related signatures. In CAPRA-S-adjusted Cox sensitivity analyses excluding recurrence-time-0 cases, higher adjacent-tissue B-cell activity was associated with reduced recurrence risk in PCBN (HR 0.42, 95% CI 0.19-0.94; BH-adjusted p=0.035) and BM (HR 0.54, 95% CI 0.30-0.95; BH-adjusted p=0.034). Tissue-based validation showed that CD19 B-cell density in adjacent benign tissue was higher in no-event than event-positive patients (median 0.1145 vs 0.0471; p=0.008). BRIGADE achieved an AUC of 0.68 in cross-validation and 0.83 in independent validation, compared to AUCs of 0.54-0.63 and 0.44-0.78 for the tested clinical predictors, respectively. At the fixed classification threshold, the validation-cohort odds ratio for BRIGADE was 2.75. The adjacent B-cell score remained associated with lower odds of a postoperative PSA event after adjustment for PSA and Gleason score. ConclusionsB-cell infiltration in tumor-adjacent benign prostate tissue may complement existing clinicopathologic models for stratifying adverse postoperative PSA outcomes and subsequent BCR after radical prostatectomy. The transcriptomic signal was recapitulated by CD19-based tissue staining, supporting further development of a pathology-based assay.
ER -