JU INSIGHT: Role of Lactate Dehydrogenase in Identifying Relapse for Patients With Stage I Testicular Cancer on Surveillance

By: Adam Bobrowski, MD; Lynn Anson-Cartwright, MSc; Kopika Kuhathaas, HBSc; Di Maria Jiang, MD, MSc; Peter Chung, MD, BCh; Philippe Bedard, MD; Padraig Warde, MBChB, BAO; Martin O’Malley, MD, BCh; Joan Sweet, MD; Robert J. Hamilton, MD, MPH | Posted on: 01 Dec 2022

Bobrowski A, Anson-Cartwright L, Kopika Kuhathaas, et al. Role of lactate dehydrogenase in identifying relapse for patients with stage I testicular cancer on surveillance. J Urol. 2022; 208(6):1250-1258.

Study Need and Importance

Tumor markers alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase (LDH) assume a key role in the management of testicular germ cell tumors (GCTs). Nonetheless, the value of LDH as a marker for disease recurrence and its role in the surveillance of patients with clinical stage I (CSI) testicular GCT has been questioned. Our study sought to better understand the utility of LDH as an independent predictor in determining testicular GCT relapse among CSI seminomas and nonseminomas (NSGCTs) on surveillance, and assessing the incidence of LDH elevation among nonrelapsing patients.

Table. Questionnaire Response by Phone Versus Clinic for All Patients (N = 86)

	Mean
	Phone response	Clinic response	Mean difference (95% CI)	P value
UDI-6 questionnaire
Total score (0-18)	6.9 (6, 7.8)	6.4 (5.5, 7.4)	0.4 (−0.1, 1.0)	.10
Q1: Frequency (0-3)	1.7 (1.5, 1.9)	1.5 (1.2, 1.7)	0.2 (0.0, 0.4)	.033
Q2: Urgency (0-3)	1.3 (1.1, 1.6)	1.3 (1, 1.5)	0.0 (−0.2, 0.2)	.81
Q3: Stress (0-3)	0.9 (0.7, 1.2)	1.1 (0.8, 1.3)	−0.1 (−0.3, 0.0)	.13
Q4: Leakage (0-3)	1 (0.8, 1.2)	1 (0.8, 1.2)	0.0 (−0.1, 0.2)	.78
Q5: Emptying (0-3)	1 (0.7, 1.2)	0.9 (0.7, 1.1)	0.1 (−0.1, 0.2)	.44
Q6: Pain (0-3)	0.9 (0.7, 1.2)	0.8 (0.5, 1)	0.2 (−0.0, 0.3)	.13
IIQ-7 questionnaire
Total score (0-21)	3.8 (2.8, 4.8)	4.2 (3.1, 5.4)	−0.5 (−1.3, 0.4)	.26
Q1: Household chores (0-3)	0.4 (0.2, 0.5)	0.4 (0.2, 0.6)	−0.1 (−0.2, 0.1)	.36
Q2: Physical recreation (0-3)	0.7 (0.5, 1)	0.6 (0.4, 0.8)	0.1 (−0.1, 0.3)	.45
Q3: Entertainment activities (0-3)	0.4 (0.3, 0.6)	0.5 (0.3, 0.7)	−0.1 (−0.3, 0.1)	.42
Q4: Travel by car (0-3)	0.6 (0.4, 0.8)	0.5 (0.3, 0.7)	0.1 (−0.1, 0.3)	.31
Q5: Social activities (0-3)	0.4 (0.2, 0.6)	0.5 (0.3, 0.7)	−0.1 (−0.3, 0.1)	.27
Q6: Emotional health (0-3)	0.5 (0.3, 0.7)	0.6 (0.4, 0.8)	−0.2 (−0.4, 0.0)	.12
Q7: Frustration (0-3)	0.9 (0.6, 1.1)	1.1 (0.8, 1.3)	−0.2 (−0.4, −0.0)	.036
Quality of life (0-10)	5 (4.3, 5.7)	4.6 (3.9, 5.2)	0.3 (−0.3, 1.0)	.28
Abbreviations: CI, confidence interval; IIQ-7, International Incontinence Questionnaire-Short Form; Q, question; UDI-6, Urinary Distress Inventory-Short Form. Questionnaires scores are reported using the 0-3 scale of the subdomains. Bolded P values are statistically significant.

What We Found

We undertook a retrospective cohort study at our high-volume center examining patients from December 1980 to May 2021. We found that LDH was never the sole indicator of relapse for either seminoma or NSGCT cohorts (see Figure). Additionally, approximately half of the nonrelapsing seminoma patients and three-quarters of nonrelapsing NSGCT patients on surveillance experienced potentially anxiety-provoking LDH elevations, with a quarter to half of these including multiple elevations.

Limitations

This is a single-center, retrospective review. While patients were followed on surveillance algorithms, these assessments were not as regimented as a prospective protocol. Additionally, as global awareness of the lack of utility of LDH increased, an isolated LDH finding may not have prompted a full investigation into relapse. However, this bias is mitigated since only 23%-28% of relapses had any associated LDH elevation always paired with either abnormal imaging or elevations in alpha-fetoprotein/human chorionic gonadotropin. We thus feel our findings are robust.

Interpretation for Patient Care

LDH does not independently contribute to relapse detection during surveillance of patients with CSI seminoma or NSGCT, and LDH elevations among nonrelapsing patients were documented in high proportions in both disease states. Our institution has thus eliminated measuring LDH in our CSI surveillance algorithms. These results highlight the ongoing need for better biomarkers to serve this population.