Serum testosterone reduction during targeted therapies for mRCC.
Mosca Alessandra1, Porta Camillo2, Martignoni Guido3, Ficarra Vincenzo4, Andorno Silvano5,
Aimaretti Gianluca6, Alabiso Oscar1, Terrone Carlo7.
Medical Oncology, 5Statistics, 6Endocrinology, 7Urology, “Maggiore della Carità” University
Hospital, East Piedmont University “A. Avogadro”, Novara, Italy
2
Medical Oncology, IRCCS, San Matteo University Hospital Foundation, Pavia, Italy.
3
Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
4
Department of Urology, University of Udine, Udine, Italy.
1
Introduction & objectives: The primary objective of this study was to assess the variations of
serum testosterone (TST), sexual hormone-binding globulin (SHBG) and thyroid-stimulating
hormone (TSH) during targeted therapies in mRCC male pts. The secondary objective was to
observe androgen, estrogen and progesterone receptor expression in tissue specimens derived from
radical nephrectomies (RN).
Materials & methods: We prospectively evaluated serum levels of TST, SHBG and TSH, at
baseline and after 1 and 2 months of therapy, in 43 consecutive male pts with mRCC (89% clear
cell, 9% papillary, 2% mixed), submitted to Sunitinib (63%), Pazopanib (7%), Sorafenib (16%) and
Everolimus (14%), as I line (81%), II line (14%) and III line (5%) treatment. Furthermore, we
retrospectively assessed androgen, estrogen and progesterone receptors in 64 tissue microarray
specimens of pts submitted to RN.
Results: After 1 and 2 months of therapy, TST significantly decreased (mean values: baseline
316.83 ng/dl; after 1 month 250.82 ng/dl; after 2 months 262.81 ng/dl; p=0.017); SHBG
significantly increased (mean values: baseline 30.88 mmol/l; after 1 month 37.41 mmol/l; after 2
months 40.61 mmol/l; p=0.0007); and, as expected, TSH significantly increased (mean Log values:
baseline 0.82 μUI/ml; after 1 month 1.10 μUI/ml; after 2 months 1.31 μUI/ml; p=0.0052).
Immunoistochemical analysis of RN revealed androgen receptors in 12/64 (19%) of specimens,
progesterone receptors in 1/64 (0.6%) of tissues and no expression of estrogen receptors (0%).
Discussion: Several antiangiogenic therapies have been recently approved for metastatic renal cell
carcinoma (mRCC), targeting the vascular endothelial growth factor axis or the mammalian target
of rapamycin pathway. Efficacy of these agents is largely demonstrated, but toxicity profile may
lack of exhaustive clinical data. Fatigue is experienced up to 77% of patients (pts) receiving
antiangiogenic agents. Hypogonadism contributes to frequent symptoms in cancer pts, including
fatigue, anorexia, depression, and sexual dysfunction. We demonstrate a significant decrease in
serum testosterone level during targeted therapies that could affect quality of life of the patients.
Conclusion: Sunitinib, Pazopanib, Sorafenib, Everolimus caused a statistical significant
suppression of TST levels, with simultaneous offsetting increase of SHBG, in male pts treated for
mRCC. The hypogonadism secondary to antiangiogenic treatment may contribute to fatigue often
described by pts as a serious adverse event. Androgen receptors expression in RN has to be
carefully evaluated when TST replacement is considered.