Summary Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8 + T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4 + T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4 + T cell states that are clonally expanded. These CD4 + T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4 + T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.
Purpose-Early intervention for prostate cancer is associated with excellent long-term survival, but many affected men, especially those with low-risk disease characteristics, might not suffer adverse impact to quantity or quality of life were treatment deferred. We sought to characterize temporal trends in clinical presentation and primary disease management among patients with low-risk prostate cancer.Methods-Data were abstracted from CaPSURE, a disease registry of 8685 men with various stages of prostate cancer. 2078 men were included who were diagnosed between 1989 and 2001 and had a serum prostate specific antigen (PSA) ≤ 10 ng/ml, Gleason sum ≤ 6, and clinical Tstage ≤ 2a. Trends in risk distribution, tumor characteristics, and primary treatment were evaluated.
BACKGROUND.Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early‐stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance.METHODS.All men who were managed initially with active surveillance were identified through the authors' institutional database. Selection criteria for active surveillance included: prostate‐specific antigen (PSA) <10 ng/mL, biopsy Gleason sum ≤6 with no pattern 4 or 5, cancer involvement of <33% of biopsy cores, and clinical stage T1/T2a tumor. Patients were followed with PSA measurements and digital rectal examination every 3 to 6 months and with transrectal ultrasound at 6‐ to 12‐month intervals. Beginning in 2003, patients also underwent repeat prostate biopsy at 12 to 24 months. The primary outcome measured was active treatment. Evidence of disease progression, defined as an increase in rebiopsy Gleason sum or significant PSA velocity changes (>0.75 ng/mL per year), was a secondary outcome. Chi‐square and log‐rank tests were used to compare groups. The association between clinical characteristics and receipt of active treatment was analyzed by using Cox proportional hazards regression.RESULTS.Three hundred twenty‐one men (mean age [±standard deviation]: 63.4 ± 8.5 years) selected active surveillance as their initial management. The overall median follow‐up was 3.6 years (range, 1–17 years). The initial mean PSA level was 6.5 ± 3.9 ng/mL. One hundred twenty men (37%) met at least 1 criterion for progression. Overall, 38% of men had higher grade on repeat biopsy, and 26% of men had a PSA velocity >0.75 ng/mL per year. Seventy‐eight men (24%) received secondary treatment at a median 3 years (range, 1–17 years) after diagnosis. Approximately 13% of patients with no disease progression elected to obtain treatment. PSA density at diagnosis and rise in Gleason score on repeat biopsy were associated significantly with receipt of secondary treatment. The disease‐specific survival rate was 100%.CONCLUSIONS.Selected individuals with early‐stage prostate cancer may be candidates for active surveillance. Specific criteria can be and need to be developed to select the most appropriate individuals for this form of management and to monitor disease progression. A small attrition rate can be expected because of men who are unable or unwilling to tolerate surveillance. Cancer 2008. © 2008 American Cancer Society.
A B S T R A C T PurposeActive surveillance (AS) is an option for the initial management of early-stage prostate cancer. Current risk stratification schema identify patients with low-risk disease who are presumed to be most suitable for AS. However, some men with higher risk disease also elect AS; outcomes for such men have not been widely reported. ; log-rank P ϭ .88). Among men undergoing surgery, none were node positive and none had biochemical recurrence within 3 years. Patients and Methods ConclusionSelected men with intermediate-risk features be appropriate candidates for AS, and are not necessarily more likely to progress. AS for these men may provide an opportunity to further reduce overtreatment of disease that is unlikely to progress to advanced cancer.
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