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  • br Discussion Our review underlines


    Discussion Our review underlines the paucity of evidence underpinning the inclusion of AFP, HCG, and LDH in international guidelines for the surveillance of testicular cancer recurrence [7]. The heterogeneity of the included studies, small sample sizes and the lack of contemporary data preclude any firm conclusions about the accuracy of these biomarkers to detect recurrent testicular cancer. The current literature, therefore, remains inadequate to determine whether there is a subgroup of patients under surveillance for recurrent disease for which a follow-up strategy based on biomarkers (alone, or in combination) could provide an alternative cost-effective means of reducing the intensity of follow-up investigations and hospital episodes included in contemporary multi-modal follow-up. A general observation is that the specificity of AFP or HCG alone is typically high (90–100%) and, except for some small studies, the sensitivity is much lower, implying that many recurrences would be missed (false negatives) using biomarker assessment alone at the cut-point adopted. The specificity and sensitivity of LDH appeared low in the three studies that reported it [[24], [25], [26]]. The limited data may support the use of biomarkers in combination, as together AFP and HCG appear to have higher sensitivity and lower specificity for seminoma and NSGCT recurrence than when used individually. Marker Benazepril varies between NSGCTs, reflecting the histological heterogeneity of these tumours, so using a combination of biomarkers may increase rates of detection. However, no evidence was found for the use of LDH in combination with AFP and HCG in relation to any tumour type. LDH is a ubiquitous enzyme, and rises are also seen in other sources of tissue damage, such as inflammation [27]. The lack of evidence on the most efficient multimodal follow-up schedule has been highlighted before [9,28]. The resultant variation in follow-up intensity and composition between institutions is often dependent on judgements based on primary tumour stage, histological composition and treatment history [8,9,29,30]. Following concerns over the risks of serial imaging and the financial burden caused by frequent diagnostic evaluations, research into more efficient follow-up is now taking place. Evidence from a randomized controlled trial led to the recommendation to reduce CT frequency from five times to twice per year in years 1–2 of NSGCT follow-up [31,32]. Physical examination has been shown to provide little additional clinical information when used alongside CT [31]. A recent retrospective analysis of two follow-up cohorts led to the recommendation that, in the context of timely cross-sectional imaging, chest radiographs no longer add any value in the routine surveillance of stage I testicular cancer [14]. However, Reading fram remains unclear from the literature what is the incremental value in using biomarkers in addition to cross-sectional imaging: studies from the early 1980’s are cited to justify the necessity for biomarkers to avoid false-negative CT examinations [29,[33], [34], [35]]. Although imaging techniques have improved since that time and more recent papers have been published looking at biomarker levels at time of recurrence [36], we retrieved no studies examining the role of biomarkers in relation to modern cross-sectional imaging techniques such as Positron Emission Tomography (PET-CT), that has shown greater sensitivity and specificity for detecting active disease than conventional CT [6]. Some authors have called for routine surveillance of tumour markers to be discontinued given the minimal evidence for detecting early recurrence [37], although it is important to emphasise also that lack of published evidence does not necessarily imply lack of utility as seen from direct clinical experience. Nevertheless, tumour markers continue to be recommended on the basis that they will infrequently identify recurrent disease which might otherwise have been missed, despite the fact the cost implications and false positive rates remain poorly defined [38]. A less intensive, evidence-based, multimodal follow-up strategy in primary care could reduce health care costs, potential harms of over-testing, and the patient anxiety associated with hospital follow-up.