Serum Tumour Markers in Testicular Germ Cell Tumours: Frequencies of Elevated Levels and Extents of Marker Elevation Are Significantly Associated with Clinical Parameters and with Response to Treatment

Abstract

Introduction. Although serum tumor markers beta human chorionic gonadotropin (bHCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are well-established tools for the management of testicular germ cell tumours (GCTs), there are only few data from contemporary cohorts of primary GCT patients regarding these biomarkers. Our aim was to evaluate marker elevations in testicular GCTs and to document their associations with various clinical characteristics.Patients and Methods. A total of 422 consecutive patients with GCTs were retrospectively analysed regarding serum levels of bHCG, AFP, and LDH during the course of treatment. Additionally, the following characteristics were recorded: histology, age, laterality, clinical stage (CS), pT-stage, and tumour size. Marker elevations were first tabulated in dichotomized way (elevated: yes/no) in various subgroups and second as continuous measured serum values. Descriptive statistical methods were employed to look for differences among subgroups and for associations of elevations with clinical parameters.Results. In all GCT patients, the frequencies of elevated levels of bHCG, AFP, LDH, and bHCG or AFP were 37.9%, 25.6%, 32.9%, and 47.6%; in pure seminomas 28%, 2.8%, 29.1%, and 30.3%; and in nonseminoma 53.0%, 60.1%, 38.7%, and 73.8%. Significant associations were noted with pT-stages >pT1, clinical stages >CS1, tumour size, and younger age. Frequencies of marker elevations dropped significantly after treatment, but LDH levels remained elevated in 30.5%-34.1%. Relapsing patients (n=27) had elevated levels of bHCG, AFP, and LDH in 25.9%, 22.2%, and 29.6%, respectively, thirteen of whom with a changed marker pattern.Conclusions. The classical GCT-biomarkers correlate with treatment success. Clinical utility is limited due to proportions of < 50% of patients with elevated levels and the low specificity of LDH. The elevation rates are significantly associated with histology, clinical and pT-stages, tumour size, and younger age. Individual marker patterns may change upon relapse. Clinically, ideal biomarkers are yet to be found.

Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up―A Copenhagen Experience

“…The most important diagnostic gain of using miRNAs is in patients with seminomas, since β-HCG is only elevated in a subset of these patients and LDH is not a reliable tumor marker (30-50% [7,10]). Accordingly, in our study, the STMs showed a sensitivity of 31% for diagnosing primary seminomas, whereas the miRNAs (miR-371a-3p and/or miR-372-3p and/or miR-373-3p) had a sensitivity of 71%.…”

“…To establish whether measuring miRNAs adds value beyond the primary diagnosis, large prospective clinical trials comparing miRNAs and classical tumor markers during the treatment and follow-up of TGCT patients are needed.Cancers 2020, 12, 759 2 of 16 HCG; 7 days for AFP). A major problem is, however, that the STMs are only elevated in 48-60% of TGCT cases at primary diagnosis, irrespective of histological type [4][5][6][7].As an alternative, or in addition to, the STMs, a panel of circulating microRNAs (miR-367-3p, miR-371a-3p, miR-372-3p, and miR-373-3p) has been investigated intensively, due to their high expression in most TGCTs (except teratomas). These miRNAs have been proposed as novel biomarkers that could replace the STMs in the clinical management of patients with TGCTs (for reviews, see Almstrup et al [8], Lobo et al [9] and Murray et al [6]).…”

“…Cancers 2020, 12, 759 2 of 16 HCG; 7 days for AFP). A major problem is, however, that the STMs are only elevated in 48-60% of TGCT cases at primary diagnosis, irrespective of histological type [4][5][6][7].…”

Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor

“…Serum levels of microRNAs (miRs) of the clusters miR-371-373 and miR-302/367 have been suggested as novel biomarkers of testicular germ cell tumors (GCTs) [1][2][3]. Of the candidate miRs, miR-371a-3p appears to be the most promising serum marker of GCT with a sensitivity of 90.1% and specificity of 94.1% [4,5] outperforming the classical markers (alpha fetoprotein, beta human chorionic gonadotropin, lactate dehydrogenase) with their sensitivities of less than 50% [6]. Apparently, miR-371a-3p features almost all of the qualities a valuable tumor marker is supposed to have [7] since it correlates with clinical stages, and tumor sizes, it highlights response (or non-response) to therapy, and it is present in cases with relapsing GCT suggesting a prominent role of this miR upon follow-up examinations [8][9][10][11][12][13][14][15].…”

Serum Level of microRNA-375-3p Is Not a Reliable Biomarker of Teratoma

“…A major limitation of these biomarkers is that they are differently expressed in the various histological subgroups of GCTs. In seminoma, the most frequent subgroup, bHCG and LDH are expressed in roughly 30% of cases, while AFP is not (2). In nonseminoma, the other main subgroup, all three markers are expressed in 30-60% of cases (3,4).…”