Value of Supraregional Multidisciplinary Review for the Contemporary Management of Testicular Tumors

Purshouse, Karin; Watson, Robert A.; Church, David N.; Richardson, Charlotte; Crane, Gemma Louise; Traill, Zoë; Sullivan, M.; Roberts, Ian; Browning, Lisa; Turner, Gareth D. H.; Parameshwaran, Vishnu; Joseph, Johnson; Chitnis, Meenali M.; Protheroe, Andrew; Verrill, Clare

doi:10.1016/j.clgc.2016.05.005

Cited by 26 publications

(16 citation statements)

References 16 publications

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“…In a series of 221 patients by Harari et al , reporting of LVI changed in 22% of cases after central pathology review. Purshouse et al reported that in 7.2% of patients with NSGCT the tumour prognostic factors were changed after central pathology review (5% for LVI status, 2.2% for EC >50% vs <50%). These discrepancies emphasise the need for pathology review by an expert genitourinary pathologist.…”

Section: Discussionmentioning

confidence: 99%

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta‐analysis

et al. 2020

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Objective To systematically review the literature on the prognostic value of lymphovascular invasion (LVI) and embryonal carcinoma (EC) for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour (CS I NSGCT). Materials and methods The PubMed, Embase (OVID) and SCOPUS databases were searched up to March 2019. Studies reporting on the association between LVI and/or EC and occult metastatic disease were considered for inclusion. The quality and risk of bias were evaluated by the Quality in Prognosis Studies tool. Results We screened 5287 abstracts and 207 full‐text articles. We included 35 studies in the narrative synthesis and 24 studies in a meta‐analysis. LVI showed the strongest effect. Pooled rates of occult metastasis were 47.5% and 16.9% for LVI‐positive and LVI‐negative patients, respectively (odds ratio [OR] 4.33, 95% confidence interval [CI] 3.55–5.30; P < 0.001). Pooled rates of occult metastasis were 33.2% for EC presence and 16.2% for EC absence (OR 2.49, 95% CI 1.64–3.77; P < 0.001). Pooled rates of occult metastasis were 40.0% for EC >50% and 20.0% for EC <50% (OR 2.62, 95% CI 1.93–3.56; P < 0.001). Conclusions LVI is the strongest risk factor for relapse. The prognostic value of EC is high, but there is no common agreement on how to define this risk factor. Both EC presence and EC >50% have similar ORs for occult metastasis. This shows that the assessment of EC presence is sufficient for the classification of EC.

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Section: Discussionmentioning

confidence: 99%

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta‐analysis

et al. 2020

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“…Assessment of this risk status has been largely dependent on histopathological variables, with vascular invasion being the most consistent prognostic tool for predicting disease relapse [22]. However, disagreements in scoring vascular invasion exist, more evident between peripheral and centralized centers with expertise on germ cell tumors, and these could result in over-and undertreatment [17,18,33]. Surveillance strategies are increasingly being employed in the approach to testicular germ cell tumor patients, given the outstanding cure rates of stage I disease with orchiectomy alone [6].…”

Section: Discussionmentioning

confidence: 99%

Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers

et al. 2020

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Background: Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables. We aimed to assess the prognostic value of previously suggested biomarkers, related to proliferation (MIB-1 and TEX19) and to immune microenvironment (CXCL12, CXCR4, beta-catenin and MECA-79) in a surveillance cohort of stage I testicular germ cell tumor patients. Methods: A total of 70 patients were included. Survival analyses were performed, including Cox regression models. Results: Patients with vascular invasion and elevated human chorionic gonadotropin levels showed significantly poorer relapse-free survival in multivariable analysis (hazard ratio = 2.820, 95% confidence interval 1.257-6.328; hazard ratio = 3.025, 95% confidence interval 1.345-6.808). Patients with no vascular invasion but with MIB-1 staining in > 50% tumor cells showed significantly shorter relapse-free survival (p = 0.042). TEX19 nuclear immunoexpression was confirmed in spermatogonial cells, and weak cytoplasmic immunoexpression was depicted in 15/70 tumors, not significantly impacting survival. CXCL12 immunoexpression in tumor cells did not associate with relapse, but non-seminoma patients exhibiting vascular invasion and CXCL12-positive stromal/inflammatory cells showed significantly improved relapse-free survival (p = 0.015). Exclusively nuclear immunoexpression of CXCR4 associated with better relapse-free survival (p = 0.032), but not after adjusting for vascular invasion. Patients with higher beta-catenin scores showed a tendency for poorer relapse-free survival (p = 0.056). MECA-79 immunoexpression was absent. Conclusions: The informative protein biomarkers (i.e., MIB-1, CXCL12, beta-catenin, and possibly CXCR4) may prove useful for risk-stratifying patients if validated in larger, multicentric and well-defined studies. Currently, classical histopathological features of testicular germ cell tumors remain key for relapse prediction.

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“…In fact, the most significant disagreement between these kinds of centers relates to vascular invasion interpretation (especially in nonseminoma cases), putting in evidence that the reproducibility on reporting this parameter by pathologists is far from ideal. [30][31][32] In current guidelines, there is no formal indication for staining with vascular markers in order to aid the detection of vascular invasion, nor is it mandatory to discriminate the type of vessel invasion present in a tumor (either lymph vessel invasion, blood vessel invasion, or both). 24,33 However, studies dealing with this matter in testicular germ cell tumors are lacking, and this was stated as the reason for not establishing a recommendation on the topic in the last International Society of Urological Pathology (ISUP) Testicular Cancer Consultation Cancer Recommendations meeting.…”

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confidence: 99%

Interobserver Agreement in Vascular Invasion Scoring and the Added Value of Immunohistochemistry for Vascular Markers to Predict Disease Relapse in Stage I Testicular Nonseminomas

Lobo

Stoop

Gillis

et al. 2019

American Journal of Surgical Pathology

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Vascular invasion has been identified as an informative risk factor for relapse in stage I testicular nonseminomas, used to tailor treatment. We investigated interobserver agreement in vascular invasion reporting and studied the potential additional value of immunohistochemistry for vascular markers for predicting relapse. Patients (n = 52) with stage I testicular nonseminomas undergoing surveillance (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006) were included (median follow-up of 66 mo). Two formalin-fixed paraffinembedded blocks with > 1 cm 2 tissue and tumor/normal parenchyma interface were stained with hematoxylin and eosin and CD31, FVIII, and D2-40. Slides were assessed by 3 independent testicular germ cell tumor-dedicated pathologists, and agreement was assessed using Cohen κ statistic. Sensitivity, specificity, and accuracy of vascular invasion scoring in predicting relapse were calculated. Agreement among testicular germ cell tumordedicated pathologists was moderate (κ = 0.49 to 0.54), as was performance in predicting disease relapse (particularly, specificity of 86%). Immunohistochemistry increased overall sensitivity (71%), but decreased specificity (71%) in predicting relapse. All patients (n = 8) with both blood and lymphatic vascular invasion developed a relapse. In multivariable analysis (including age, tumor size, rete testis invasion, and serum tumor markers), only vascular invasion had an independent impact in predicting relapse. Assessment of vascular invasion by testicular germ cell tumor-dedicated pathologists is good and is clinically meaningful, predicting disease relapse. Immunohistochemistry for vascular markers improves sensitivity of detecting disease relapse and allows for the identification of high-risk patients with both blood and lymphatic vascular invasion simultaneously, potentially of interest for tailored chemotherapy.

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Value of Supraregional Multidisciplinary Review for the Contemporary Management of Testicular Tumors

Cited by 26 publications

References 16 publications

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta‐analysis

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta‐analysis

Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers

Interobserver Agreement in Vascular Invasion Scoring and the Added Value of Immunohistochemistry for Vascular Markers to Predict Disease Relapse in Stage I Testicular Nonseminomas

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