Predictive role of γ-glutamyltransferase in patients receiving nivolumab therapy for metastatic renal cell carcinoma

A Systematic Review of Serum γ-Glutamyltransferase as a Prognostic Biomarker in Patients with Genitourinary Cancer

“…Similar findings were also reported in other organs, including the uterus [81][82][83][84][85], colorectum [86], ovaries [23], esophagus [87,88], breasts [89,90], gallbladder [91], nasopharynx [92,93], stomach [74,94], lungs [95], and pancreas [96]. In urogenital organs, too, recent studies have demonstrated that serum GGT can predict survival in patients with advanced GU cancer, including RCC [11,12], PC [13], and UC [14]. Thus, it can be speculated that serum GGT has the potential to become a general biomarker of the tumor burden in patients with GU cancer, given that tumors arising from the urogenital organs overexpress GGT [46], possibly leading to its release into the bloodstream and its presence in the serum of patients with a metastatic disease in particular.…”

“…It is worth noting that the results of the six studies of RCC were often contradictory; one study enrolling a relatively small patient cohort with heterogeneous clinicopathological demographics (n = 80) showed that elevated serum GGT was observed only in patients with RCC with non-bone metastases but did not predict the survival of the patients [7] while another study enrolling 700 patients with non-metastatic RCC revealed that serum GGT predicted metastasis-free survival but not overall survival or cancer-specific survival [9]. In contrast, the remaining four studies of RCC that included patients with metastatic RCC or RCC with a venous tumor thrombus demonstrated a significant association between the pre-therapeutic serum GGT level on both univariable and multivariable analyses [8,[10][11][12]. Studies of patients with metastatic PC or advanced UC also revealed that elevated serum GGT was independently associated with shorter overall survival [13,14].…”

“…Elevated serum GGT was more predictive of the prognosis of advanced diseases [8,[10][11][12][13][14] than of early stage diseases [7]. It may therefore be hypothesized that the heavy tumor burden is required for GGT overexpression by cancer cells to become detectable in the serum of patients (Figure 4).…”

“…Moreover, a subset of RCC patients with elevated GGT in preoperative serum samples showed a significant decrease in the post-operative serum GGT level [11]. Furthermore, early changes in serum GGT levels during the first two months of nivolumab therapy as well as the baseline serum GGT level were significantly associated with survival in patients with metastatic RCC [12]. An important question is whether the level of systemic serum GGT directly reflects the level of local GGT expression in cancer patients.…”

“…Moreover, serum GGT is reportedly associated with a poor prognosis in patients with liver cancer, reflecting unfavorable clinicopathological features, including vascular invasion and the tumor burden, as demonstrated in previous meta-analyses [5,6]. Subsequently, serum GGT was also found to be a significant prognostic biomarker in patients with a variety of malignant neoplasms; however, reports of serum GGT in relation to genitourinary (GU) cancer are relatively limited, and the findings among studies of renal cell carcinoma (RCC) are sometimes contradictory depending on the metastatic status of the disease [7][8][9][10][11][12]. On the other hand, serum GGT was found to be significantly and independently associated with shorter overall survival in patients with advanced GU cancer, such as metastatic prostate cancer (PC) and advanced urothelial carcinoma (UC) [13,14].…”