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Background Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer. Patients and Methods Men with localized or metastatic prostate cancer were included in this study. Cytokine serum levels including interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, monocyte chemotactic protein 1 (CCL-2), tumor necrosis factor α, and growth-regulated oncogene α (CXCL-1) using a multiplex enzyme-linked immunosorbent assay and T. vaginalis serology were measured in blood samples at diagnosis. Results A total of 324 patients were identified at time of localized disease and 118 at time of metastatic disease. Of the 189 patients with localized disease and clinical follow-up data (median, 73 months), 28 developed lethal disease. There was no association between circulating cytokine levels above median concentrations nor T. vaginalis seropositivity and risk of intermediate- to high-risk or lethal prostate cancer. Conclusion Higher levels of serum cytokine levels and T. vaginalis seropositivity at diagnosis are not associated with high-grade or lethal prostate cancer and do not aid risk stratification of localized prostate cancer.

The development of immune checkpoint inhibitors (ICI) has dramatically changed the landscape of therapies for metastatic renal cell carcinoma. However, many patients do not benefit from such therapy and prognostic or predictive validated biomarker validated for ICI are still needed to better select and treat patient. Plasmatic soluble immune checkpoints have been described as potential immune biomarkers in hematological malignancies and solids tumors, then, we would like to explore the prognostic value of different soluble immune checkpoints in patients with mRCC treated with nivolumab after TKI. We prospectively collected plasma samples before nivolumab infusion from 38 patients previously treated for mRCC with TKI at Paoli-Calmettes Institute, from the NIVOREN GETUG-AFU 26 study (NCT03013335). Enzyme-linked immunosorbent assays (ELISA) were performed for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3A1 and BTN2A1. Among the different soluble checkpoints analyzed, only high baseline plasmatic level of BTN2A1 was significantly associated with shorter PFS: median PFS was 3.95 months for sBTN2A1high vs 14.30 months for sBTN2A1low (sBTN2A1 cut-off: 6.7ng/mL; HR = 2.26, 95%CI [0.68 – 4.60], p = 0.0307). There was no statistical difference in OS between sBTN2A1high and sBTN2A1low. Our results suggest that the baseline level of plasmatic BTN2A1 could be an independent prognosis factor of PFS after nivolumab for pre-treated patient with mRCC. However, these results need to be validated in a larger prospective cohort and the biological role of BTN subfamily and γδ T cell immunity in mRCC must be elucidated.

One of the standard management options for high-risk localized prostate cancer is radiotherapy combined with long-term androgen deprivation therapy. Trials involving chemotherapy or next-generation hormone therapies in combination with a local treatment are ongoing for this specific subgroup.

Background High-dose chemotherapy (HDCT) with autologous stem-cell transplantation (aSCT) has been a standard therapy for relapsed metastatic germ-cell tumors (GCTs) over the last 2 decades, but there have been many changes in practice over time with respect to stem-cell source, mobilization, and conditioning regimens. Mobilization is impaired with greater cisplatin exposure. Patients and Methods Patients with relapsed GCT who received HDCT/aSCT at Dana-Farber Cancer Institute between 1997 and 2017 were identified. Diagnosis, first-line chemotherapy, stem-cell mobilization, HDCT, toxicity, and survival outcomes were annotated and descriptively summarized. Univariable associations of clinicopathologic features and relapse and survival were assessed. Time-to-event analyses were performed by HDCT type and duration. Results Thirty-five eligible patients were identified. The most common regimen before HDCT was paclitaxel, ifosfamide, and cisplatin, and it resulted in a high rate of successful initial mobilization (95%). Ten patients (29%) were mobilized with filgrastim and plerixafor (CXCR4 antagonist). All plerixafor-treated patients were mobilized with sufficient cells for 2 transplants. Oxazaphosphorine (cyclophosphamide or ifosfamide)-containing (O-C) HDCT was provided between 1997 and 2008, and subsequent patients were treated with high-dose carboplatin plus etoposide (CE). O-C HDCT was associated with excessive cardiac (33%), severe liver (93%), and renal dysfunction compared to CE. Two O-C–treated patients died of drug-related lung toxicity. Fifty-one percent of the cohort experienced relapse, and 46% died. Conclusion Plerixafor has a role in stem-cell mobilization and aSCT for relapsed GCT when cisplatin in bridging before HDCT may be problematic. O-C and CE HDCT regimens have different toxicity patterns that are clinically meaningful.

Monoclonal antibodies targeting immune checkpoint molecules CTLA-4, PD-1 or PD-L1 are emerging as promising anticancer therapeutics in multiple cancer subtypes resulting in remarkable and long-lasting clinical responses. These immune checkpoint blockers (ICBs) have already obtained approval for the treatment of patients with metastatic melanoma, advanced/refractory non-small cell lung cancer and renal cell cancer. ICBs enhance immune responses against cancer cells but can also lead to inflammatory side effects called immune-related adverse events (irAEs). Such toxicities are distinct from those associated with traditional chemotherapeutic agents or molecularly targeted therapies. Although severe irAEs remain rare (~10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. As malignancies are frequently diagnosed in older patients, ICB treatment of elderly presents a unique challenge. However, the knowledge about efficacy and toxicity of these molecules in this specific population is limited, as most of the studies have involved a low number of older patients. In this review, we will discuss about the different ICB efficacy data available for older patients. We will then highlight the specific spectrum of immunotherapy toxicities and talk about their management in the context of older adults.