Publication date: July 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 7
Author(s): Georg C. Hutterer, Florian Posch, Lorenz Buser, Richard Zigeuner, Laura Morshäuser, Wolfgang Otto, Peter J. Wild, Maximilian Burger, Matthias May, Martin Pichler, Sabine D. Brookman-May
Abstract
Background
To externally validate‚ BioScore’, a biomarker-based scoring system using immunohistochemical tumor expression levels of B7-H1, survivin, and Ki-67, in a single-center cohort of renal cell carcinoma (RCC) patients. Additionally, we investigated the potential benefit of BioScore as compared to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score.
Materials and Methods
The validation cohort comprised 393 nonmetastatic RCC patients treated with radical nephrectomy or nephron-sparing surgery from 1999 to 2004. Kaplan-Meier estimators, the log-rank test, uni- and multivariable Cox regression models, and measures of discrimination were used to quantify the prognostic performance of BioScore regarding cancer-specific mortality (CSM).
Results
During a median follow-up of 7.8 years, 69/132 (52%) deaths were adjudicated to progressive disease. BioScore was weakly associated with CSM in univariable analysis (hazard ratio per 1 point increase = 1.12, 95% confidence interval = 1.02–1.23, P = 0.023). However, this association did not prevail after adjusting for other adverse prognostic factors as represented by the SSIGN score. The discriminative performance of BioScore was very modest (Harrell's C-Index = 0.60) and did not improve the SSIGN score (P = 0.341), which already showed an excellent discrimination, as evidenced by Harrell's C-Index of 0.81. In a sensitivity analysis regarding clear cell RCC patients only, B7-H1 positivity did not emerge as a statistically significant predictor of CSM.
Conclusion
Although a higher BioScore was significantly associated with a higher CSM, the magnitude of this association was weak and not independent from other prognosticators. Moreover, BioScore did not improve the prognostic accuracy of the SSIGN score.
Publication date: July 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 7
Author(s): Zuzana Strizova, Pavla Taborska, Dmitry Stakheev, Simona Partlová, Klara Havlova, Stepan Vesely, Jirina Bartunkova, Daniel Smrz
Abstract
Objectives
Renal cell carcinoma (RCC) is the most lethal urologic malignancy with increasing incidence worldwide. The conventional treatment strategies for advanced or recurrent RCC are not efficient and show considerable toxicities. Adoptive cell transfer (ACT) has become a promising treatment option for multiple cancers, particularly in combination with other therapeutic approaches. ACT often utilizes extensively in vitro expanded tumor-infiltrating lymphocytes (TILs). However, TILs are a very heterogeneous mix of cell populations and only those populations that have a cytotoxic and migratory potential are thought to deliver a therapeutic impact in ACT. The identification and localization of these therapeutically potent populations are therefore needed.
Methods and materials
A total number of 57 tissue samples from 19 RCC patients who underwent radical nephrectomy was analyzed. The tissue samples were obtained from the tumor, peritumoral tissue, and the adjacent healthy renal tissue. The tissues were sliced, enzymatically dissociated into single cell suspensions and the obtained cells further analyzed by flow cytometry for the expression of markers of lymphocyte cytotoxicity – TRAIL and FasL, and a surrogate marker of lymphocyte migratory activity – PECAM-1. The analyzed data were next correlated with the clinical and histopathological data.
Results
Non-clear cell RCC (non-ccRCC) tumors showed a significantly decreased tumor infiltration with TRAIL+FasL+ NK cells but elevated infiltration with FasL+PECAM-1+ T cells as compared with clear cell RCC (ccRCC) tumors. Further analyses revealed that the peritumoral tissue of ccRCC patients is a reservoir of TRAIL+FasL+, TRAIL+PECAM-1+, or FasL+PECAM-1+ NK and T cells.
Conclusions
The cytotoxic/migratory lymphocytes were identified in tumors of ccRCC patients. These lymphocytes became excluded from the tumor and accumulated in the patient's peritumoral tissue.
Publication date: July 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 7
Author(s): Kohei Hashimoto, Hidetoshi Tabata, Tetsuya Shindo, Toshiaki Tanaka, Jiro Hashimoto, Ryuta Inoue, Takashi Muranaka, Hiroshi Hotta, Masahiro Yanase, Yasuharu Kunishima, Atsushi Takahashi, Naoya Masumori, on behalf of the Sapporo Medical University Urologic Oncology Consortium (SUOC)
Abstract
Objective
Our aim was to evaluate the usefulness of serum testosterone to guide treatment decision for castration-resistant prostate cancer (CRPC).
Methods
We conducted a retrospective analysis of 115 patients with CRPC treated with either abiraterone (n = 43) or enzalutamide (n = 72). A serum testosterone level was measured at time of starting of abiraterone or enzalutamide. We determined whether serum testosterone influenced the outcomes of androgen receptor (AR)-targeted therapy.
Results
In the very-low testosterone group (<5 ng/dl), the rate of prostate-specific antigen (PSA) response was significantly higher among patients treated with abiraterone compared to enzalutamide (62 vs. 32%, respectively; P = 0.033), with no difference in the low testosterone group (5–<50 ng/dl) (93 vs. 81%, respectively; P = 0.429). During the median follow-up of 26 months, PSA progression-free survival was significantly longer in the low testosterone group than in the very-low testosterone group (12.2 vs. 4.5 months, P<0.001). In the very-low testosterone group, enzalutamide use (HR 3.07, 95% CI 1.36–6.94; P = 0.007), primary androgen deprivation therapy <12 months (HR 2.50, 95% CI 1.23–5.08; P = 0.011) and bone metastases (HR 2.60, 95% CI 1.20–5.64; P = 0.015) were significantly associated with PSA progression.
Conclusion
Patients with a serum testosterone level ≥5 ng/dl were more likely to receive therapeutic benefits from AR-targeted therapy compared to those with serum testosterone levels <5 ng/dl. However, even for those with a very low serum testosterone level, the efficacy of abiraterone was slightly higher than that of enzalutamide. Therefore, serum testosterone level is a useful biomarker for informing treatment selection for CRPC.