Biomarkers of disease recurrence in stage I testicular germ cell tumours.
Journal
Nature reviews. Urology
ISSN: 1759-4820
Titre abrégé: Nat Rev Urol
Pays: England
ID NLM: 101500082
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
accepted:
29
06
2022
pubmed:
27
8
2022
medline:
5
11
2022
entrez:
26
8
2022
Statut:
ppublish
Résumé
Stage I testicular cancer is a disease restricted to the testicle. After orchiectomy, patients are considered to be without disease; however, the tumour is prone to relapse in ~4-50% of patients. Current predictive markers of relapse, which are tumour size and invasion to rete testis (in seminoma) or lymphovascular invasion (in non-seminoma), have limited clinical utility and are unable to correctly predict relapse in a substantial proportion of patients. Adjuvant therapeutic strategies based on available biomarkers can lead to overtreatment of 50-85% of patients. Discovery and implementation of novel biomarkers into treatment decision making will help to reduce the burden of adjuvant treatments and improve patient selection for adjuvant therapy.
Identifiants
pubmed: 36028719
doi: 10.1038/s41585-022-00624-y
pii: 10.1038/s41585-022-00624-y
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
637-658Informations de copyright
© 2022. Springer Nature Limited.
Références
Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2021. CA Cancer J. Clin. 71, 7–33 (2021).
pubmed: 33433946
doi: 10.3322/caac.21654
Amin, M. B., et al. AJCC Cancer Staging Manual (Springer, 2017).
Kamran, S. C. et al. A review of clinical stage 1 testicular cancer mortality in a high-volume center. J. Clin. Oncol. 33, 390–390 (2015).
doi: 10.1200/jco.2015.33.7_suppl.390
Dong, W., Gang, W., Liu, M. & Zhang, H. Analysis of the prognosis of patients with testicular seminoma. Oncol. Lett. 11, 1361–1366 (2016).
pubmed: 26893743
doi: 10.3892/ol.2015.4065
Moch, H., Cubilla, A. L., Humphrey, P. A., Reuter, V. E. & Ulbright, T. M. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur. Urol. 70, 93–105 (2016).
pubmed: 26935559
doi: 10.1016/j.eururo.2016.02.029
Skakkebaek, N. E. Possible carcinoma-in-situ of the testis. Lancet 2, 516–517 (1972).
pubmed: 4115573
doi: 10.1016/S0140-6736(72)91909-5
Looijenga, L. H. Testicular germ cell tumors. Pediatr. Endocrinol. Rev. 11 (Suppl. 2), 251–262 (2014).
pubmed: 24683949
Yamashita, S. et al. Trends in age and histology of testicular cancer from 1980–2019: a single-center study. Tohoku J. Exp. Med. 252, 219–224 (2020).
pubmed: 33148936
doi: 10.1620/tjem.252.219
Dieckmann, K. P. et al. Testicular germ-cell tumours: a descriptive analysis of clinical characteristics at first presentation. Urol. Int. 100, 409–419 (2018).
pubmed: 29649815
doi: 10.1159/000488284
Rothermundt, C. et al. Baseline characteristics and patterns of care in testicular cancer patients: first data from the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS). Swiss Med. Wkly. 148, w14640 (2018).
pubmed: 30044478
Arturo Enrique, M. G., Joel, J. A., Luis Eduardo, S. S., Arturo, D. H. & Laura Denisse, R. G. Embryonal carcinoma metastasis from pure testicular teratoma mimicking a complex renal cyst. Urol. Case Rep. 34, 101481 (2021).
pubmed: 33204644
doi: 10.1016/j.eucr.2020.101481
Vugrin, D., Chen, A., Feigl, P. & Laszlo, J. Embryonal carcinoma of the testis. Cancer 61, 2348–2352 (1988).
pubmed: 3365662
doi: 10.1002/1097-0142(19880601)61:11<2348::AID-CNCR2820611133>3.0.CO;2-H
Talerman, A., Haije, W. G. & Baggerman, L. Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP. Cancer 46, 380–385 (1980).
pubmed: 6155988
doi: 10.1002/1097-0142(19800715)46:2<380::AID-CNCR2820460228>3.0.CO;2-U
Howitt, B. E. & Berney, D. M. Tumors of the testis: morphologic features and molecular alterations. Surg. Pathol. Clin. 8, 687–716 (2015).
pubmed: 26612222
doi: 10.1016/j.path.2015.07.007
Hedinger, C., von Hochstetter, A. R. & Egloff, B. Seminoma with syncytiotrophoblastic giant cells. A special form of seminoma. Virchows Arch. A Pathol. Anat. Histol. 383, 59–67 (1979).
pubmed: 157614
doi: 10.1007/BF00427010
Niehans, G. A., Manivel, J. C., Copland, G. T., Scheithauer, B. W. & Wick, M. R. Immunohistochemistry of germ cell and trophoblastic neoplasms. Cancer 62, 1113–1123 (1988).
pubmed: 2457424
doi: 10.1002/1097-0142(19880915)62:6<1113::AID-CNCR2820620614>3.0.CO;2-0
Khan, S., Jetley, S., Pujani, M. & Neogi, S. Pure yolk sac tumor of testis in an adult: a rare occurrence. J. Postgrad. Med. 60, 351–353 (2014).
pubmed: 25121392
Kattuoa, M. & Kumar, A. in StatPearls (2021).
Schmoll, H. J. et al. European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann. Oncol. 15, 1377–1399 (2004).
pubmed: 15319245
doi: 10.1093/annonc/mdh301
Alvarado-Cabrero, I., Hernandez-Toriz, N. & Paner, G. P. Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis. Am. J. Surg. Pathol. 38, 111–118 (2014).
pubmed: 24145647
doi: 10.1097/PAS.0b013e3182a2926e
Simmonds, P. D. et al. Primary pure teratoma of the testis. J. Urol. 155, 939–942 (1996).
pubmed: 8583612
doi: 10.1016/S0022-5347(01)66352-3
Stevens, M. J. et al. Prognosis of testicular teratoma differentiated. Br. J. Urol. 73, 701–706 (1994).
pubmed: 8032840
doi: 10.1111/j.1464-410X.1994.tb07560.x
Ueno, T. et al. Spectrum of germ cell tumors: from head to toe. Radiographics 24, 387–404 (2004).
pubmed: 15026588
doi: 10.1148/rg.242035082
Taza, F. et al. Prognostic value of teratoma in primary tumor and postchemotherapy retroperitoneal lymph node dissection specimens in patients with metastatic germ cell tumor. J. Clin. Oncol. 38, 1338–1345 (2020).
pubmed: 32134699
pmcid: 7840096
doi: 10.1200/JCO.19.02569
Carver, B. S., Al-Ahmadie, H. & Sheinfeld, J. Adult and pediatric testicular teratoma. Urol. Clin. North. Am. 34, 245–251 (2007).
pubmed: 17484929
doi: 10.1016/j.ucl.2007.02.013
Chakrabarti, P. R. et al. Histopathological trends of testicular neoplasm: an experience over a decade in a tertiary care centre in the Malwa belt of Central India. J. Clin. Diagn. Res. 10, EC16–EC18 (2016).
pubmed: 27504294
pmcid: 4963654
Krag Jacobsen, G. et al. Testicular germ cell tumours in Denmark 1976–1980. Pathology of 1058 consecutive cases. Acta Radiol. Oncol. 23, 239–247 (1984).
pubmed: 6093440
doi: 10.3109/02841868409136019
Go, J. H. Pure choriocarcinoma of testis with tumor-infiltrating lymphocytes and granulomas. Yonsei Med. J. 47, 887–891 (2006).
pubmed: 17191322
pmcid: 2687833
doi: 10.3349/ymj.2006.47.6.887
Sheikine, Y. et al. Molecular genetics of testicular germ cell tumors. Am. J. Cancer Res. 2, 153–167 (2012).
pubmed: 22432056
pmcid: 3304567
Nicholls, P. K. & Page, D. C. Germ cell determination and the developmental origin of germ cell tumors. Development https://doi.org/10.1242/dev.198150 (2021).
doi: 10.1242/dev.198150
pubmed: 33913479
Muller, M. R., Skowron, M. A., Albers, P. & Nettersheim, D. Molecular and epigenetic pathogenesis of germ cell tumors. Asian J. Urol. 8, 144–154 (2021).
pubmed: 33996469
doi: 10.1016/j.ajur.2020.05.009
Baroni, T., Arato, I., Mancuso, F., Calafiore, R. & Luca, G. On the origin of testicular germ cell tumors: from gonocytes to testicular cancer. Front. Endocrinol. 10, 343 (2019).
doi: 10.3389/fendo.2019.00343
Skakkebaek, N. E., Berthelsen, J. G., Giwercman, A. & Muller, J. Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int. J. Androl. 10, 19–28 (1987).
pubmed: 3034791
doi: 10.1111/j.1365-2605.1987.tb00161.x
Boileau, M. A. & Steers, W. D. Testis tumors: the clinical significance of the tumor-contaminated scrotum. J. Urol. 132, 51–54 (1984).
pubmed: 6726960
doi: 10.1016/S0022-5347(17)49460-2
Markland, C., Kedia, K. & Fraley, E. E. Inadequate orchiectomy for patients with testicular tumors. JAMA 224, 1025–1026 (1973).
pubmed: 4739918
doi: 10.1001/jama.1973.03220210041009
Werntz, R. P. & Eggener, S. E. Defining risk of micrometastatic disease and tumor recurrence in patients with stage I testicular germ cell tumors. Transl. Androl. Urol. 9, S31–S35 (2020).
pubmed: 32055483
pmcid: 6995846
doi: 10.21037/tau.2019.06.20
Gilligan, T. et al. Testicular cancer, version 2.2020, NCCN clinical practice guidelines in oncology. J. Natl Compr. Cancer Netw. 17, 1529–1554 (2019).
doi: 10.6004/jnccn.2019.0058
Oldenburg, J. et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 24 (Suppl. 6), vi125–vi132 (2013).
pubmed: 24078656
doi: 10.1093/annonc/mdt304
M.P. Laguna (Chair), et al. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan (EAU, 2021).
Mazzone, E. et al. Contemporary assessment of long-term survival rates in patients with stage I nonseminoma germ-cell tumor of the testis: population-based comparison between surveillance and active treatment after initial orchiectomy. Clin. Genitourin. Cancer 17, e1153–e1162 (2019).
pubmed: 31515197
doi: 10.1016/j.clgc.2019.08.009
Petrelli, F. et al. Surveillance or adjuvant treatment with chemotherapy or radiotherapy in stage I seminoma: a systematic review and meta-analysis of 13 studies. Clin. Genitourin. Cancer 13, 428–434 (2015).
pubmed: 25959904
doi: 10.1016/j.clgc.2015.04.005
Cummins, S., Yau, T., Huddart, R., Dearnaley, D. & Horwich, A. Surveillance in stage I seminoma patients: a long-term assessment. Eur. Urol. 57, 673–678 (2010).
pubmed: 19545941
doi: 10.1016/j.eururo.2009.06.006
Sogani, P. C. et al. Clinical stage I testis cancer: long-term outcome of patients on surveillance. J. Urol. 159, 855–858 (1998).
pubmed: 9474168
doi: 10.1016/S0022-5347(01)63753-4
Kollmannsberger, C. et al. Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy. Ann. Oncol. 21, 1296–1301 (2010).
pubmed: 19875756
doi: 10.1093/annonc/mdp473
Kollmannsberger, C. et al. Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance. J. Clin. Oncol. 33, 51–57 (2015).
pubmed: 25135991
doi: 10.1200/JCO.2014.56.2116
Sturgeon, J. F. et al. Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital’s experience. Eur. Urol. 59, 556–562 (2011).
pubmed: 21190791
doi: 10.1016/j.eururo.2010.12.010
Tandstad, T. et al. Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA). Ann. Oncol. 27, 1299–1304 (2016).
pubmed: 27052649
doi: 10.1093/annonc/mdw164
Nappi, L., Nichols, C. R. & Kollmannsberger, C. K. New treatments for stage I testicular cancer. Clin. Adv. Hematol. Oncol. 15, 626–631 (2017).
pubmed: 28949950
Groll, R. J., Warde, P. & Jewett, M. A. A comprehensive systematic review of testicular germ cell tumor surveillance. Crit. Rev. Oncol. Hematol. 64, 182–197 (2007).
pubmed: 17644403
doi: 10.1016/j.critrevonc.2007.04.014
Kersh, C. R. et al. Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy. Cancer 65, 2681–2685 (1990).
pubmed: 2160316
doi: 10.1002/1097-0142(19900615)65:12<2681::AID-CNCR2820651214>3.0.CO;2-V
Leman, E. S. & Gonzalgo, M. L. Prognostic features and markers for testicular cancer management. Indian. J. Urol. 26, 76–81 (2010).
pubmed: 20535291
pmcid: 2878444
doi: 10.4103/0970-1591.60450
Albers, P. et al. Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial. J. Clin. Oncol. 21, 1505–1512 (2003).
pubmed: 12697874
doi: 10.1200/JCO.2003.07.169
Fung, C. Y., Kalish, L. A., Brodsky, G. L., Richie, J. P. & Garnick, M. B. Stage I nonseminomatous germ cell testicular tumor: prediction of metastatic potential by primary histopathology. J. Clin. Oncol. 6, 1467–1473 (1988).
pubmed: 2843611
doi: 10.1200/JCO.1988.6.9.1467
Gilbert, D. C. et al. Defining a new prognostic index for stage I nonseminomatous germ cell tumors using CXCL12 expression and proportion of embryonal carcinoma. Clin. Cancer Res. 22, 1265–1273 (2016).
pubmed: 26453693
doi: 10.1158/1078-0432.CCR-15-1186
Li, X. et al. Surveillance for patients with clinical stage I nonseminomatous testicular germ cell tumors. World J. Urol. 33, 1351–1357 (2015).
pubmed: 25471669
doi: 10.1007/s00345-014-1454-7
Akaza, H., Kameyama, S. & Aso, Y. [Significance of tumor markers in the treatment of urological malignancies]. Gan To Kagaku Ryoho 14, 3034–3040 (1987).
pubmed: 2445294
Gels, M. E. et al. Detection of recurrence in patients with clinical stage I nonseminomatous testicular germ cell tumors and consequences for further follow-up: a single-center 10-year experience. J. Clin. Oncol. 13, 1188–1194 (1995).
pubmed: 7537802
doi: 10.1200/JCO.1995.13.5.1188
Azizi, M., Peyton, C. C., Boulware, D. C., Gilbert, S. M. & Sexton, W. J. Primary tumor size thresholds in stage IA testicular seminoma: Implications for adjuvant therapy after orchiectomy and survival. Urol. Oncol. 38, 7.e9–7.e18 (2020).
doi: 10.1016/j.urolonc.2019.09.022
Blok, J. M. et al. 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. BJU Int. 125, 355–368 (2020).
pubmed: 31797520
pmcid: 7065076
doi: 10.1111/bju.14967
Daugaard, G. et al. Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort. J. Clin. Oncol. 32, 3817–3823 (2014).
pubmed: 25267754
doi: 10.1200/JCO.2013.53.5831
Read, G. et al. Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J. Clin. Oncol. 10, 1762–1768 (1992).
pubmed: 1403057
doi: 10.1200/JCO.1992.10.11.1762
Mortensen, M. S. et al. A nationwide cohort study of stage I seminoma patients followed on a surveillance program. Eur. Urol. 66, 1172–1178 (2014).
pubmed: 25064686
doi: 10.1016/j.eururo.2014.07.001
Nichols, C. R. et al. Active surveillance is the preferred approach to clinical stage I testicular cancer. J. Clin. Oncol. 31, 3490–3493 (2013).
pubmed: 24002502
doi: 10.1200/JCO.2012.47.6010
Yu, H. Y., Madison, R. A., Setodji, C. M. & Saigal, C. S. Quality of surveillance for stage I testis cancer in the community. J. Clin. Oncol. 27, 4327–4332 (2009).
pubmed: 19652075
pmcid: 2744273
doi: 10.1200/JCO.2008.19.9406
Hamilton, R. J. et al. Treatment of relapse of clinical stage I nonseminomatous germ cell tumors on surveillance. J. Clin. Oncol. 37, 1919–1926 (2019).
pubmed: 30802156
doi: 10.1200/JCO.18.01250
Chandran, E. A., Chindewere, A., North, R. & Jameson, M. B. Two cycles of adjuvant carboplatin for clinical stage 1 testicular seminoma in New Zealand centres: a retrospective analysis of efficacy and long-term events. Cancer Rep. 4, e1310 (2021).
Chau, C. et al. Treatment outcome and patterns of relapse following adjuvant carboplatin for stage I testicular seminomatous germ-cell tumour: results from a 17-year UK experience. Ann. Oncol. 26, 1865–1870 (2015).
pubmed: 26037797
doi: 10.1093/annonc/mdv254
Dieckmann, K. P. et al. Adjuvant treatment of clinical stage I seminoma: is a single course of carboplatin sufficient? Urology 55, 102–106 (2000).
pubmed: 10654903
doi: 10.1016/S0090-4295(99)00376-3
Dieckmann, K. P. et al. Testicular seminoma clinical stage 1: treatment outcome on a routine care level. J. Cancer Res. Clin. Oncol. 142, 1599–1607 (2016).
pubmed: 27116691
pmcid: 4899489
doi: 10.1007/s00432-016-2162-z
Diminutto, A. et al. Adjuvant carboplatin treatment in 115 patients with stage I seminoma: retrospective multicenter survey. Clin. Genitourin. Cancer 14, e161–e169 (2016).
pubmed: 26775721
doi: 10.1016/j.clgc.2015.12.009
Oliver, R. T. et al. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J. Clin. Oncol. 29, 957–962 (2011).
pubmed: 21282539
doi: 10.1200/JCO.2009.26.4655
Powles, T. et al. The long-term risks of adjuvant carboplatin treatment for stage I seminoma of the testis. Ann. Oncol. 19, 443–447 (2008).
pubmed: 18048383
doi: 10.1093/annonc/mdm540
Ruf, C. G. et al. Adjuvant carboplatin therapy in patients with clinical stage 1 testicular seminoma: is long-term morbidity increased? J. Cancer Res. Clin. Oncol. 145, 2335–2342 (2019).
pubmed: 31286241
doi: 10.1007/s00432-019-02965-5
Albers, P. et al. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J. Clin. Oncol. 26, 2966–2972 (2008).
pubmed: 18458040
doi: 10.1200/JCO.2007.12.0899
Tandstad, T. et al. One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group. Ann. Oncol. 25, 2167–2172 (2014).
pubmed: 25114021
doi: 10.1093/annonc/mdu375
Hiester, A. et al. Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection — a 13-year follow-up analysis of a phase III trial cohort. Eur. J. Cancer 155, 64–72 (2021).
pubmed: 34371444
doi: 10.1016/j.ejca.2021.06.022
Hiester, A. et al. Late toxicities and recurrences in patients with clinical stage I nonseminomatous germ cell tumor after one cycle of adjuvant BEP versus primary retroperitoneal lymph node dissection: a 13-years follow-up analysis of a phase III trial cohort. J. Clin. Oncol. 38, 5512–5512 (2020).
doi: 10.1200/JCO.2020.38.15_suppl.5512
Capocaccia, R., Gatta, G. & Dal Maso, L. Life expectancy of colon, breast, and testicular cancer patients: an analysis of US-SEER population-based data. Ann. Oncol. 26, 1263–1268 (2015).
pubmed: 25735314
doi: 10.1093/annonc/mdv131
Fischer, S. et al. Outcome of men with relapses after adjuvant bleomycin, etoposide, and cisplatin for clinical stage I nonseminoma. J. Clin. Oncol. 38, 1322–1331 (2020).
pubmed: 31877087
doi: 10.1200/JCO.19.01876
Stutzman, R. E. & McLeod, D. G. Radiation therapy: a primary treatment modality for seminoma. Urol. Clin. North. Am. 7, 757–764 (1980).
pubmed: 7456184
doi: 10.1016/S0094-0143(21)00166-X
De Felice, F., Musio, D., Gravina, G. L., Marampon, F. & Tombolini, V. Adjuvant radiation therapy in stage I seminoma: 20 years of oncologic results. Oncotarget 7, 80077–80082 (2016).
pubmed: 27556300
pmcid: 5346772
doi: 10.18632/oncotarget.11374
Soper, M. S. et al. Observation versus adjuvant radiation or chemotherapy in the management of stage I seminoma: clinical outcomes and prognostic factors for relapse in a large US cohort. Am. J. Clin. Oncol. 37, 356–359 (2014).
pubmed: 23275274
doi: 10.1097/COC.0b013e318277d839
Leung, E. et al. Treatment burden in stage I seminoma: a comparison of surveillance and adjuvant radiation therapy. BJU Int. 112, 1088–1095 (2013).
pubmed: 23937685
doi: 10.1111/bju.12330
Chan, R. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I testicular seminoma: a report on Medical Research Council Trial TE18, European Organisation for Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J. Clin. Oncol. 23, 6806 (2005). author reply 6806-6807.
pubmed: 16170196
doi: 10.1200/JCO.2005.01.8978
Fung, C., Fossa, S. D., Beard, C. J. & Travis, L. B. Second malignant neoplasms in testicular cancer survivors. J. Natl Compr. Cancer Netw. 10, 545–556 (2012).
doi: 10.6004/jnccn.2012.0052
Travis, L. B. et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J. Natl Cancer Inst. 97, 1354–1365 (2005).
pubmed: 16174857
doi: 10.1093/jnci/dji278
Chovanec, M. et al. Late adverse effects and quality of life in survivors of testicular germ cell tumour. Nat. Rev. Urol. 18, 227–245 (2021).
pubmed: 33686290
doi: 10.1038/s41585-021-00440-w
Chovanec, M. et al. Long-term sexual functioning in germ-cell tumor survivors. BMC Cancer 20, 779 (2020).
pubmed: 32819309
pmcid: 7439516
doi: 10.1186/s12885-020-07301-6
van den Belt-Dusebout, A. W. et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J. Clin. Oncol. 25, 4370–4378 (2007).
pubmed: 17906202
doi: 10.1200/JCO.2006.10.5296
Donohue, J. P. & Foster, R. S. Retroperitoneal lymphadenectomy in staging and treatment. The development of nerve-sparing techniques. Urol. Clin. North. Am. 25, 461–468 (1998).
pubmed: 9728215
doi: 10.1016/S0094-0143(05)70035-5
Donohue, J. P., Thornhill, J. A., Foster, R. S., Rowland, R. G. & Bihrle, R. Retroperitoneal lymphadenectomy for clinical stage A testis cancer (1965 to 1989): modifications of technique and impact on ejaculation. J. Urol. 149, 237–243 (1993).
pubmed: 8381190
doi: 10.1016/S0022-5347(17)36046-9
Donohue, J. P., Thornhill, J. A., Foster, R. S., Rowland, R. G. & Bihrle, R. Clinical stage B non-seminomatous germ cell testis cancer: the Indiana University experience (1965–1989) using routine primary retroperitoneal lymph node dissection. Eur. J. Cancer 31A, 1599–1604 (1995).
pubmed: 7488408
doi: 10.1016/0959-8049(95)00330-L
Hermans, B. P., Sweeney, C. J., Foster, R. S., Einhorn, L. E. & Donohue, J. P. Risk of systemic metastases in clinical stage I nonseminoma germ cell testis tumor managed by retroperitoneal lymph node dissection. J. Urol. 163, 1721–1724 (2000).
pubmed: 10799168
doi: 10.1016/S0022-5347(05)67528-3
Klepp, O. et al. Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group. J. Clin. Oncol. 8, 509–518 (1990).
pubmed: 1689773
doi: 10.1200/JCO.1990.8.3.509
McLeod, D. G. et al. Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study. J. Urol. 145, 1178–1183 (1991). discussion 1182–1183.
pubmed: 1851890
doi: 10.1016/S0022-5347(17)38567-1
Nicolai, N. et al. Retroperitoneal lymph node dissection with no adjuvant chemotherapy in clinical stage I nonseminomatous germ cell tumours: long-term outcome and analysis of risk factors of recurrence. Eur. Urol. 58, 912–918 (2010).
pubmed: 20817343
doi: 10.1016/j.eururo.2010.08.032
Nicolai, N. et al. A simple model for predicting nodal metastasis in patients with clinical stage I nonseminomatous germ cell testicular tumors undergoing retroperitoneal lymph node dissection only. J. Urol. 171, 172–176 (2004).
pubmed: 14665870
doi: 10.1097/01.ju.0000101513.64777.f2
Beck, S. D., Bey, A. L., Bihrle, R. & Foster, R. S. Ejaculatory status and fertility rates after primary retroperitoneal lymph node dissection. J. Urol. 184, 2078–2080 (2010).
pubmed: 20850817
doi: 10.1016/j.juro.2010.06.146
Mayer, F., Honecker, F., Looijenga, L. H. & Bokemeyer, C. Towards an understanding of the biological basis of response to cisplatin-based chemotherapy in germ-cell tumors. Ann. Oncol. 14, 825–832 (2003).
pubmed: 12796018
doi: 10.1093/annonc/mdg242
Sheinfeld, J. & Motzer, R. J. Stage I testicular cancer management and necessity for surgical expertise. J. Clin. Oncol. 26, 2934–2936 (2008).
pubmed: 18458042
doi: 10.1200/JCO.2008.16.0416
Stephenson, A. J. et al. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J. Clin. Oncol. 23, 2781–2788 (2005).
pubmed: 15837993
doi: 10.1200/JCO.2005.07.132
Warde, P. et al. Prognostic factors for relapse in stage I testicular seminoma treated with surveillance. J. Urol. 157, 1705–1709 (1997). discussion 1709–1710.
pubmed: 9112510
doi: 10.1016/S0022-5347(01)64839-0
Warde, P. et al. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J. Clin. Oncol. 20, 4448–4452 (2002).
pubmed: 12431967
doi: 10.1200/JCO.2002.01.038
Pierorazio, P. M. et al. Comparative effectiveness of surveillance, primary chemotherapy, radiotherapy and retroperitoneal lymph node dissection for the management of early stage testicular germ cell tumors: a systematic review. J. Urol. 205, 370–382 (2021).
pubmed: 32915080
doi: 10.1097/JU.0000000000001364
Boormans, J. L. et al. Testicular tumour size and rete testis invasion as prognostic factors for the risk of relapse of clinical stage I seminoma testis patients under surveillance: a systematic review by the Testicular Cancer Guidelines Panel. Eur. Urol. 73, 394–405 (2018).
pubmed: 29100813
doi: 10.1016/j.eururo.2017.09.025
Chung, P. et al. Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance. Cancer Med. 4, 155–160 (2015).
pubmed: 25236854
doi: 10.1002/cam4.324
Parker, C. et al. The prognostic significance of the tumour infiltrating lymphocyte count in stage I testicular seminoma managed by surveillance. Eur. J. Cancer 38, 2014–2019 (2002).
pubmed: 12376206
doi: 10.1016/S0959-8049(02)00235-6
Aparicio, J. et al. Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG). Ann. Oncol. 25, 2173–2178 (2014).
pubmed: 25210015
doi: 10.1093/annonc/mdu437
Tandstad, T. et al. Management of seminomatous testicular cancer: a binational prospective population-based study from the Swedish Norwegian testicular cancer study group. J. Clin. Oncol. 29, 719–725 (2011).
pubmed: 21205748
doi: 10.1200/JCO.2010.30.1044
Zengerling, F. et al. Prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance — a systematic review. Urol. Oncol. 36, 448–458 (2018).
pubmed: 28712790
doi: 10.1016/j.urolonc.2017.06.047
Fontes-Sousa, M. et al. Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification. BMC Urol. 20, 127 (2020).
pubmed: 32819326
pmcid: 7439661
doi: 10.1186/s12894-020-00682-7
Nayan, M. et al. Conditional risk of relapse in surveillance for clinical stage I testicular cancer. Eur. Urol. 71, 120–127 (2017).
pubmed: 27527805
doi: 10.1016/j.eururo.2016.07.013
von der Maase, H. et al. Surveillance following orchidectomy for stage I seminoma of the testis. Eur. J. Cancer 29A, 1931–1934 (1993).
pubmed: 8280484
doi: 10.1016/0959-8049(93)90446-M
Scandura, G. et al. Pathological risk factors for metastatic disease at presentation in testicular seminomas with focus on the recent pT changes in AJCC TNM eighth edition. Hum. Pathol. 94, 16–22 (2019).
pubmed: 31666197
doi: 10.1016/j.humpath.2019.10.004
Perry, A., Wiley, E. L. & Albores-Saavedra, J. Pagetoid spread of intratubular germ cell neoplasia into rete testis: a morphologic and histochemical study of 100 orchiectomy specimens with invasive germ cell tumors. Hum. Pathol. 25, 235–239 (1994).
pubmed: 7512072
doi: 10.1016/0046-8177(94)90193-7
Berney, D. M. et al. Handling and reporting of orchidectomy specimens with testicular cancer: areas of consensus and variation among 25 experts and 225 European pathologists. Histopathology 67, 313–324 (2015).
pubmed: 25619976
pmcid: 5026308
doi: 10.1111/his.12657
Charitopoulos, K. et al. in Clinical Genitourinary Pathology: a case-based learning approach (ed. Lazaris, A. C.) 397–530 (Springer International Publishing, 2018).
French, B. L. & Zynger, D. L. Do histopathologic variables affect the reporting of lymphovascular invasion in testicular germ cell tumors? Am. J. Clin. Pathol. 145, 341–349 (2016).
pubmed: 27124916
doi: 10.1093/ajcp/aqv091
Verrill, C. et al. Reporting and staging of testicular germ cell tumors: the international society of urological pathology (ISUP) testicular cancer consultation conference recommendations. Am. J. Surg. Pathol. 41, e22–e32 (2017).
pubmed: 28368923
doi: 10.1097/PAS.0000000000000844
Sharma, P., Dhillon, J., Agarwal, G., Zargar-Shoshtari, K. & Sexton, W. J. Disparities in interpretation of primary testicular germ cell tumor pathology. Am. J. Clin. Pathol. 144, 289–294 (2015).
pubmed: 26185314
doi: 10.1309/AJCPJTX8R6CVWSRW
Verrill, C. et al. Intraoperative consultation and macroscopic handling: the international society of urological pathology (ISUP) Testicular cancer consultation conference recommendations. Am. J. Surg. Pathol. 42, e33–e43 (2018).
pubmed: 29579010
doi: 10.1097/PAS.0000000000001049
Nicolai, N. et al. Concordance and prediction ability of original and reviewed vascular invasion and other prognostic parameters of clinical stage I nonseminomatous germ cell testicular tumors after retroperitoneal lymph node dissection. J. Urol. 186, 1298–1302 (2011).
pubmed: 21849196
doi: 10.1016/j.juro.2011.05.070
Purshouse, K. et al. Value of supraregional multidisciplinary review for the contemporary management of testicular tumors. Clin. Genitourin. Cancer 15, 152–156 (2017).
pubmed: 27324054
doi: 10.1016/j.clgc.2016.05.005
van Leenders, G. et al. The 2019 international society of urological pathology (ISUP) consensus conference on grading of prostatic carcinoma. Am. J. Surg. Pathol. 44, e87–e99 (2020).
pubmed: 32459716
pmcid: 7382533
doi: 10.1097/PAS.0000000000001497
Sato, Y. Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct. Funct. 26, 19–24 (2001).
pubmed: 11345500
doi: 10.1247/csf.26.19
Udager, A. M. et al. Utility of ERG immunohistochemistry for evaluation of lymphovascular invasion in testicular germ cell tumors: a retrospective pilot study. Appl. Immunohistochem. Mol. Morphol. 27, 392–401 (2019).
pubmed: 28968266
pmcid: 5876063
doi: 10.1097/PAI.0000000000000597
Lobo, J., Stoop, H., Gillis, A. J. M., Looijenga, L. H. J. & Oosterhuis, W. Interobserver agreement in vascular invasion scoring and the added value of immunohistochemistry for vascular markers to predict disease relapse in stage I testicular nonseminomas. Am. J. Surg. Pathol. 43, 1711–1719 (2019).
pubmed: 31490238
doi: 10.1097/PAS.0000000000001352
Wobser, M. et al. Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanoma. Arch. Dermatol. Res. 297, 352–357 (2006).
pubmed: 16395613
doi: 10.1007/s00403-005-0633-1
Fukunaga, M. Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology 46, 396–402 (2005).
pubmed: 15810951
doi: 10.1111/j.1365-2559.2005.02098.x
Ghosh, A. et al. The potential of artificial intelligence to detect lymphovascular invasion in testicular cancer. Cancers https://doi.org/10.3390/cancers13061325 (2021).
doi: 10.3390/cancers13061325
pubmed: 34944902
pmcid: 8699240
Andrews, P. W. et al. Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochem. Soc. Trans. 33, 1526–1530 (2005).
pubmed: 16246161
doi: 10.1042/BST0331526
Li, S. & Li, Q. Cancer stem cells and tumor metastasis (Review). Int. J. Oncol. 44, 1806–1812 (2014).
pubmed: 24691919
pmcid: 4063536
doi: 10.3892/ijo.2014.2362
Aparicio, J. et al. Multicenter study evaluating a dual policy of postorchiectomy surveillance and selective adjuvant single-agent carboplatin for patients with clinical stage I seminoma. Ann. Oncol. 14, 867–872 (2003).
pubmed: 12796024
doi: 10.1093/annonc/mdg241
Aparicio, J. et al. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study. J. Clin. Oncol. 23, 8717–8723 (2005).
pubmed: 16260698
doi: 10.1200/JCO.2005.01.9810
Aparicio, J. et al. Risk-adapted treatment in clinical stage I testicular seminoma: the third Spanish Germ Cell Cancer Group study. J. Clin. Oncol. 29, 4677–4681 (2011).
pubmed: 22042940
doi: 10.1200/JCO.2011.36.0503
Aparicio, J. et al. A risk-adapted approach to patients with stage I seminoma according to the status of rete testis: the fourth Spanish Germ Cell Cancer Group Study. Oncology 95, 8–12 (2018).
pubmed: 29587278
doi: 10.1159/000487438
Mrinakova, B. et al. Stage I testicular seminoma risk-adapted therapeutic management. Neoplasma https://doi.org/10.4149/neo_2021_200630N677 (2021).
doi: 10.4149/neo_2021_200630N677
pubmed: 33502887
Maroto, P. et al. Multicentre risk-adapted management for stage I non-seminomatous germ cell tumours. Ann. Oncol. 16, 1915–1920 (2005).
pubmed: 16126737
doi: 10.1093/annonc/mdi397
Tandstad, T. et al. Risk-adapted treatment in clinical stage I nonseminomatous germ cell testicular cancer: the SWENOTECA management program. J. Clin. Oncol. 27, 2122–2128 (2009).
pubmed: 19307506
doi: 10.1200/JCO.2008.18.8953
Ondrusova, M., Waczulikova, I., Lehotska, V., Zeleny, T. & Ondrus, D. Management of clinical stage I nonseminomatous germ cell testicular tumors: a 25-year single-center experience. Clin. Genitourin. Cancer 15, e1015–e1019 (2017).
pubmed: 28673797
doi: 10.1016/j.clgc.2017.05.023
Kamel, M. H. et al. Insurance status and differences in treatment and survival of testicular cancer patients. Urology 87, 140–145 (2016).
pubmed: 26477833
doi: 10.1016/j.urology.2015.06.059
Kuronya, Z. et al. Low socioeconomic position is a risk factor for delay to treatment and mortality of testicular cancer patients in Hungary, a prospective study. BMC Public Health 21, 1707 (2021).
pubmed: 34538241
pmcid: 8451119
doi: 10.1186/s12889-021-11720-w
Wymer, K. M. et al. Adherence to national comprehensive cancer network® guidelines for testicular cancer. J. Urol. 197, 684–689 (2017).
pubmed: 27663460
doi: 10.1016/j.juro.2016.09.073
Ilijazi, D., Shariat, S. F., Hassler, M. R., Lemberger, U. & Ertl, I. E. Epigenetic alterations of testicular germ cell tumours. Curr. Opin. Urol. 30, 264–270 (2020).
pubmed: 31905176
doi: 10.1097/MOU.0000000000000724
Boccellino, M. et al. Testicular cancer from diagnosis to epigenetic factors. Oncotarget 8, 104654–104663 (2017).
pubmed: 29262668
pmcid: 5732834
doi: 10.18632/oncotarget.20992
la Rosa, A. H., Manoharan, M. & Goolam, A. S. Current concepts of epigenetics in testicular cancer. Indian. J. Surg. Oncol. 8, 169–174 (2017).
pubmed: 28546713
pmcid: 5427031
doi: 10.1007/s13193-016-0593-2
Dominguez, G. et al. p14ARF promoter hypermethylation in plasma DNA as an indicator of disease recurrence in bladder cancer patients. Clin. Cancer Res. 8, 980–985 (2002).
pubmed: 11948103
Park, J. Y. Promoter hypermethylation in prostate cancer. Cancer Control. 17, 245–255 (2010).
pubmed: 20861812
doi: 10.1177/107327481001700405
Chovanec, M. et al. Incorporating DNA methyltransferase Inhibitors (DNMTis) in the treatment of genitourinary malignancies: a systematic review. Target. Oncol. 13, 49–60 (2018).
pubmed: 29230671
pmcid: 6428576
doi: 10.1007/s11523-017-0546-x
Dudziec, E., Gogol-Doring, A., Cookson, V., Chen, W. & Catto, J. Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells. PLoS One 7, e32750 (2012).
pubmed: 22412920
pmcid: 3296741
doi: 10.1371/journal.pone.0032750
Ramakrishnan, S. & Pili, R. Histone deacetylase inhibitors and epigenetic modifications as a novel strategy in renal cell carcinoma. Cancer J. 19, 333–340 (2013).
pubmed: 23867515
pmcid: 3766322
doi: 10.1097/PPO.0b013e3182a09e07
Argiropoulos, B. & Humphries, R. K. Hox genes in hematopoiesis and leukemogenesis. Oncogene 26, 6766–6776 (2007).
pubmed: 17934484
doi: 10.1038/sj.onc.1210760
Li, B., Huang, Q. & Wei, G. H. The role of HOX transcription factors in cancer predisposition and progression. Cancers https://doi.org/10.3390/cancers11040528 (2019).
doi: 10.3390/cancers11040528
pubmed: 31905966
pmcid: 7017032
Song, M. S. et al. The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex. Nat. Cell Biol. 6, 129–137 (2004).
pubmed: 14743218
doi: 10.1038/ncb1091
Markulin, D. et al. Association between RASSF1A promoter methylation and testicular germ cell tumor: a meta-analysis and a cohort study. Cancer Genomics Proteom. 14, 363–372 (2017).
Marchetti, A. et al. Down regulation of high in normal-1 (HIN-1) is a frequent event in stage I non-small cell lung cancer and correlates with poor clinical outcome. Clin. Cancer Res. 10, 1338–1343 (2004).
pubmed: 14977834
doi: 10.1158/1078-0432.CCR-1174-03
Krop, I. E. et al. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proc. Natl Acad. Sci. USA 98, 9796–9801 (2001).
pubmed: 11481438
pmcid: 55532
doi: 10.1073/pnas.171138398
Costa, A. L. et al. DNA methylation profiling as a tool for testicular germ cell tumors subtyping. Epigenomics 10, 1511–1523 (2018).
pubmed: 30418048
doi: 10.2217/epi-2018-0034
Lobo, J. et al. Combining hypermethylated RASSF1A detection using ddPCR with miR-371a-3p testing: an improved panel of liquid biopsy biomarkers for testicular germ cell tumor patients. Cancers https://doi.org/10.3390/cancers13205228 (2021).
doi: 10.3390/cancers13205228
pubmed: 34771419
pmcid: 8582552
Hindson, C. M. et al. Absolute quantification by droplet digital PCR versus analog real-time PCR. Nat. Methods 10, 1003–1005 (2013).
pubmed: 23995387
pmcid: 4118677
doi: 10.1038/nmeth.2633
Ahmadi, H., Jang, T. L., Daneshmand, S. & Ghodoussipour, S. Editorial by Bendu K. Konneh, John T. Lafin and Aditya Bagrodia on pp. 341-342 of this issue: microRNA-371a-3p as a blood-based biomarker in testis cancer. Asian J. Urol. 8, 400–406 (2021).
pubmed: 34765447
pmcid: 8566368
doi: 10.1016/j.ajur.2021.08.004
Hashemi Goradel, N., Najafi, M., Salehi, E., Farhood, B. & Mortezaee, K. Cyclooxygenase-2 in cancer: a review. J. Cell Physiol. 234, 5683–5699 (2019).
pubmed: 30341914
doi: 10.1002/jcp.27411
Joo, Y. E. et al. Cyclooxygenase-2 expression is associated with well-differentiated and intestinal-type pathways in gastric carcinogenesis. Digestion 66, 222–229 (2002).
pubmed: 12592098
doi: 10.1159/000068366
Wolff, H. et al. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res. 58, 4997–5001 (1998).
pubmed: 9823297
Hase, T. et al. Cyclooxygenase-1 and -2 in human testicular tumours. Eur. J. Cancer 39, 2043–2049 (2003).
pubmed: 12957459
doi: 10.1016/S0959-8049(03)00485-4
Ellinger, J. et al. CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. J. Urol. 182, 324–329 (2009).
pubmed: 19447423
doi: 10.1016/j.juro.2009.02.106
Kobayashi, K. et al. Oncological outcomes in patients with stage I testicular seminoma and nonseminoma: pathological risk factors for relapse and feasibility of surveillance after orchiectomy. Diagn. Pathol. 8, 57 (2013).
pubmed: 23566361
pmcid: 3632495
doi: 10.1186/1746-1596-8-57
Valdevenito, J. P., Gallegos, I., Fernandez, C., Acevedo, C. & Palma, R. Correlation between primary tumor pathologic features and presence of clinical metastasis at diagnosis of testicular seminoma. Urology 70, 777–780 (2007).
pubmed: 17991554
doi: 10.1016/j.urology.2007.05.020
Trevino, K. E. et al. Pathological risk factors for higher clinical stage in testicular seminomas. Histopathology 73, 741–747 (2018).
pubmed: 29858564
doi: 10.1111/his.13667
Kaminska, K. et al. Prognostic and predictive epigenetic biomarkers in oncology. Mol. Diagn. Ther. 23, 83–95 (2019).
pubmed: 30523565
doi: 10.1007/s40291-018-0371-7
Thomas, M. L. & Marcato, P. Epigenetic modifications as biomarkers of tumor development, therapy response, and recurrence across the cancer care continuum. Cancers https://doi.org/10.3390/cancers10040101 (2018).
doi: 10.3390/cancers10040101
pubmed: 30518088
pmcid: 6315759
Chovanec, M. et al. Emerging prognostic biomarkers in testicular germ cell tumors: looking beyond established practice. Front. Oncol. 8, 571 (2018).
pubmed: 30547014
pmcid: 6280583
doi: 10.3389/fonc.2018.00571
Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).
pubmed: 14744438
doi: 10.1016/S0092-8674(04)00045-5
Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).
pubmed: 19167326
pmcid: 3794896
doi: 10.1016/j.cell.2009.01.002
Pileczki, V., Cojocneanu-Petric, R., Maralani, M., Neagoe, I. B. & Sandulescu, R. MicroRNAs as regulators of apoptosis mechanisms in cancer. Clujul Med. 89, 50–55 (2016).
pubmed: 27004025
pmcid: 4777469
Noguer-Dance, M. et al. The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta. Hum. Mol. Genet. 19, 3566–3582 (2010).
pubmed: 20610438
doi: 10.1093/hmg/ddq272
Gillis, A. J. et al. High-throughput microRNAome analysis in human germ cell tumours. J. Pathol. 213, 319–328 (2007).
pubmed: 17893849
doi: 10.1002/path.2230
Palmer, R. D. et al. Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets. Cancer Res. 70, 2911–2923 (2010).
pubmed: 20332240
pmcid: 3000593
doi: 10.1158/0008-5472.CAN-09-3301
Belge, G., Dieckmann, K. P., Spiekermann, M., Balks, T. & Bullerdiek, J. Serum levels of microRNAs miR-371-3: a novel class of serum biomarkers for testicular germ cell tumors? Eur. Urol. 61, 1068–1069 (2012).
pubmed: 22386195
doi: 10.1016/j.eururo.2012.02.037
Dieckmann, K. P. et al. MicroRNAs miR-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours. Br. J. Cancer 107, 1754–1760 (2012).
pubmed: 23059743
pmcid: 3493876
doi: 10.1038/bjc.2012.469
Radtke, A. et al. The novel biomarker of germ cell tumours, micro-RNA-371a-3p, has a very rapid decay in patients with clinical stage 1. Urol. Int. 100, 470–475 (2018).
pubmed: 29698973
doi: 10.1159/000488771
Salem, M. & Gilligan, T. Serum tumor markers and their utilization in the management of germ-cell tumors in adult males. Expert. Rev. Anticancer. Ther. 11, 1–4 (2011).
pubmed: 21166503
doi: 10.1586/era.10.219
Dieckmann, K. P. et al. Serum levels of microRNA-371a-3p (M371 Test) as a new biomarker of testicular germ cell tumors: results of a prospective multicentric study. J. Clin. Oncol. 37, 1412–1423 (2019).
pubmed: 30875280
pmcid: 6544462
doi: 10.1200/JCO.18.01480
Gillis, A. J. et al. Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle. Mol. Oncol. 7, 1083–1092 (2013).
pubmed: 24012110
pmcid: 5528443
doi: 10.1016/j.molonc.2013.08.002
Leao, R. et al. Circulating microRNAs, the next-generation serum biomarkers in testicular germ cell tumours: a systematic review. Eur. Urol. 80, 456–466 (2021).
pubmed: 34175151
doi: 10.1016/j.eururo.2021.06.006
Almstrup, K. et al. Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours. Nat. Rev. Urol. 17, 201–213 (2020).
pubmed: 32157202
doi: 10.1038/s41585-020-0296-x
Morup, N., Rajpert-De Meyts, E., Juul, A., Daugaard, G. & Almstrup, K. Evaluation of circulating miRNA biomarkers of testicular germ cell tumors during therapy and follow-up — a Copenhagen experience. Cancers https://doi.org/10.3390/cancers12030759 (2020).
doi: 10.3390/cancers12030759
pubmed: 32210101
pmcid: 7140092
Anheuser, P. et al. Serum levels of microRNA371a-3p: a highly sensitive tool for diagnosing and staging testicular germ cell tumours: a clinical case series. Urol. Int. 99, 98–103 (2017).
pubmed: 28586780
doi: 10.1159/000477446
van Agthoven, T., Eijkenboom, W. M. H. & Looijenga, L. H. J. microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients. Cell Oncol. 40, 379–388 (2017).
doi: 10.1007/s13402-017-0333-9
Murray, M. J. et al. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours. Br. J. Cancer 114, 151–162 (2016).
pubmed: 26671749
doi: 10.1038/bjc.2015.429
Nappi, L. et al. Developing a highly specific biomarker for germ cell malignancies: plasma miR371 expression across the germ cell malignancy spectrum. J. Clin. Oncol. 37, 3090–3098 (2019).
pubmed: 31553692
pmcid: 7351323
doi: 10.1200/JCO.18.02057
Lobo, J. et al. Utility of serum miR-371a-3p in predicting relapse on surveillance in patients with clinical stage I testicular germ cell cancer. Eur. Urol. Oncol. https://doi.org/10.1016/j.euo.2020.11.004 (2020).
doi: 10.1016/j.euo.2020.11.004
pubmed: 33288479
Fankhauser, C. D. et al. Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours. Br. J. Cancer https://doi.org/10.1038/s41416-021-01643-z (2021).
doi: 10.1038/s41416-021-01643-z
pubmed: 34912073
Dieckmann, K. P. et al. Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1. World J. Urol. https://doi.org/10.1007/s00345-021-03876-2 (2021).
doi: 10.1007/s00345-021-03876-2
pubmed: 34854948
pmcid: 8921055
Bagrodia, A. et al. Impact of circulating microRNA test (miRNA-371a-3p) on appropriateness of treatment and cost outcomes in patients with Stage I non-seminomatous germ cell tumours. BJU Int. https://doi.org/10.1111/bju.15288 (2020).
doi: 10.1111/bju.15288
pubmed: 33124175
Dieckmann, K. P. et al. Serum levels of microRNA miR-371a-3p: a sensitive and specific new biomarker for germ cell tumours. Eur. Urol. 71, 213–220 (2017).
pubmed: 27495845
doi: 10.1016/j.eururo.2016.07.029
Vigneron, N. et al. Towards a new standardized method for circulating miRNAs profiling in clinical studies: Interest of the exogenous normalization to improve miRNA signature accuracy. Mol. Oncol. 10, 981–992 (2016).
pubmed: 27083764
pmcid: 5423189
doi: 10.1016/j.molonc.2016.03.005
Roest, H. P., IJzermans, J. N. M. & van der Laan, L. J. W. Evaluation of RNA isolation methods for microRNA quantification in a range of clinical biofluids. BMC Biotechnol. 21, 48 (2021).
pubmed: 34362351
pmcid: 8344161
doi: 10.1186/s12896-021-00706-6
Myklebust, M. P. et al. Quantitative PCR measurement of miR-371a-3p and miR-372-p is influenced by hemolysis. Front. Genet. 10, 463 (2019).
pubmed: 31191602
pmcid: 6539204
doi: 10.3389/fgene.2019.00463
Conduit, C. & Tran, B. Improving outcomes in germ cell cancers using miRNA. Ther. Adv. Med. Oncol. 13, 17588359211027826 (2021).
pubmed: 34262617
pmcid: 8252353
doi: 10.1177/17588359211027826
Vilela-Salgueiro, B. et al. Germ cell tumour subtypes display differential expression of microRNA371a-3p. Philos. Trans. R. Soc. Lond. B Biol. Sci. https://doi.org/10.1098/rstb.2017.0338 (2018).
doi: 10.1098/rstb.2017.0338
pubmed: 29685967
pmcid: 5915726
Belge, G. et al. Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor. Oncotarget 11, 1462–1473 (2020).
pubmed: 32363003
pmcid: 7185068
doi: 10.18632/oncotarget.27565
Belge, G., Grobelny, F., Matthies, C., Radtke, A. & Dieckmann, K. P. Serum level of microRNA-375-3p is not a reliable biomarker of teratoma. In Vivo 34, 163–168 (2020).
pubmed: 31882475
pmcid: 6984070
doi: 10.21873/invivo.11757
Lafin, J. T. et al. Serum small RNA sequencing and miR-375 assay do not identify the presence of pure teratoma at postchemotherapy retroperitoneal lymph node dissection. Eur. Urol. Open Sci. 26, 83–87 (2021).
pubmed: 33997822
pmcid: 8121258
doi: 10.1016/j.euros.2021.02.003
Anderson, N. M. & Simon, M. C. The tumor microenvironment. Curr. Biol. 30, R921–R925 (2020).
pubmed: 32810447
pmcid: 8194051
doi: 10.1016/j.cub.2020.06.081
Arneth, B. Tumor microenvironment. Medicina https://doi.org/10.3390/medicina56010015 (2019).
doi: 10.3390/medicina56010015
pubmed: 31906017
pmcid: 7023392
Sionov, R. V., Fridlender, Z. G. & Granot, Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron. 8, 125–158 (2015).
pubmed: 24895166
doi: 10.1007/s12307-014-0147-5
Wu, L., Saxena, S., Awaji, M. & Singh, R. K. Tumor-associated neutrophils in cancer: going pro. Cancers https://doi.org/10.3390/cancers11040564 (2019).
doi: 10.3390/cancers11040564
pubmed: 31906036
pmcid: 7017320
Horzum, U. et al. CD66b
pubmed: 32632664
doi: 10.1007/s00262-020-02656-y
Yamada, Y. et al. Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor. BMC Cancer 16, 898 (2016).
pubmed: 27863478
pmcid: 5116192
doi: 10.1186/s12885-016-2926-5
Mann, K. [Tumor markers in testicular cancer]. Urologe A 29, 77–86 (1990).
pubmed: 2158684
Dieckmann, K. P. et al. 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. Biomed. Res. Int. 2019, 5030349 (2019).
pubmed: 31275973
pmcid: 6558624
doi: 10.1155/2019/5030349
Kausitz, J., Ondrus, D., Belan, V. & Matoska, J. Monitoring of patients with non-seminomatous germ cell tumors of the testis by determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels and by computed tomography. Neoplasma 39, 357–361 (1992).
pubmed: 1283444
Norgaard-Pedersen, B. et al. Tumour markers in testicular germ cell tumours. Five-year experience from the DATECA Study 1976-1980. Acta Radiol. Oncol. 23, 287–294 (1984).
pubmed: 6208749
doi: 10.3109/02841868409136024
Venkitaraman, R. et al. The utility of lactate dehydrogenase in the follow-up of testicular germ cell tumours. BJU Int. 100, 30–32 (2007).
pubmed: 17552950
doi: 10.1111/j.1464-410X.2007.06905.x
Ackers, C. & Rustin, G. J. Lactate dehydrogenase is not a useful marker for relapse in patients on surveillance for stage I germ cell tumours. Br. J. Cancer 94, 1231–1232 (2006).
pubmed: 16622461
pmcid: 2361409
doi: 10.1038/sj.bjc.6603087
Trigo, J. M. et al. Tumor markers at the time of recurrence in patients with germ cell tumors. Cancer 88, 162–168 (2000).
pubmed: 10618619
doi: 10.1002/(SICI)1097-0142(20000101)88:1<162::AID-CNCR22>3.0.CO;2-V
Milose, J. C., Filson, C. P., Weizer, A. Z., Hafez, K. S. & Montgomery, J. S. Role of biochemical markers in testicular cancer: diagnosis, staging, and surveillance. Open Access. J. Urol. 4, 1–8 (2011).
pubmed: 24198649
pmcid: 3818947
Li, D., Mallory, T. & Satomura, S. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clin. Chim. Acta 313, 15–19 (2001).
pubmed: 11694234
doi: 10.1016/S0009-8981(01)00644-1
Leerapun, A. et al. The utility of lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: evaluation in a United States referral population. Clin. Gastroenterol. Hepatol. 5, 394–402 (2007). quiz 267.
pubmed: 17368240
pmcid: 1931510
doi: 10.1016/j.cgh.2006.12.005
Zhou, J. M., Wang, T. & Zhang, K. H. AFP-L3 for the diagnosis of early hepatocellular carcinoma: a meta-analysis. Medicine 100, e27673 (2021).
pubmed: 34713864
pmcid: 8556013
doi: 10.1097/MD.0000000000027673
Kawai, K. et al. Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity. Int. J. Urol. 12, 284–289 (2005).
pubmed: 15828957
doi: 10.1111/j.1442-2042.2005.01032.x
Kamoto, T. et al. Lectin-reactive alpha-fetoprotein (AFP-L3%) curability and prediction of clinical course after treatment of non-seminomatous germ cell tumors. Jpn. J. Clin. Oncol. 32, 472–476 (2002).
pubmed: 12499420
doi: 10.1093/jjco/hyf094
Beck, S. D., Foster, R. S., Bihrle, R. & Donohue, J. P. Significance of primary tumor size and preorchiectomy serum tumor marker level in predicting pathologic stage at retroperitoneal lymph node dissection in clinical stage A nonseminomatous germ cell tumors. Urology 69, 557–559 (2007).
pubmed: 17382165
doi: 10.1016/j.urology.2006.12.011
Wishnow, K. I. et al. Identifying patients with low-risk clinical stage I nonseminomatous testicular tumors who should be treated by surveillance. Urology 34, 339–343 (1989).
pubmed: 2480680
doi: 10.1016/0090-4295(89)90436-6
Bruns, F., Raub, M., Schaefer, U. & Micke, O. No predictive value of beta-hCG in patients with stage I seminoma-results of a long-term follow-up study after adjuvant radiotherapy. Anticancer. Res. 25, 1543–1546 (2005).
pubmed: 16033057
Weissbach, L. et al. Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group. Eur. Urol. 36, 601–608 (1999).
pubmed: 10559615
doi: 10.1159/000020055
Badia, R. R. et al. Pre-orchiectomy serum tumor markers as a predictor of recurrence in stage I germ cell tumors. J. Clin. Oncol. 39, 389–389 (2021).
doi: 10.1200/JCO.2021.39.6_suppl.389
Mouliere, F. et al. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aat4921 (2018).
doi: 10.1126/scitranslmed.aat4921
pubmed: 30404863
pmcid: 6483061
Ellinger, J. et al. Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J. Urol. 181, 363–371 (2009).
pubmed: 19010497
doi: 10.1016/j.juro.2008.08.118
Lo, Y. M. et al. Rapid clearance of fetal DNA from maternal plasma. Am. J. Hum. Genet. 64, 218–224 (1999).
pubmed: 9915961
pmcid: 1377720
doi: 10.1086/302205
Ellinger, J., Albers, P., Muller, S. C., von Ruecker, A. & Bastian, P. J. Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker. BJU Int. 104, 48–52 (2009).
pubmed: 19154496
doi: 10.1111/j.1464-410X.2008.08289.x
Farci, F. & Shamsudeen, S. in StatPearls (2022).
Yang, Q. E., Kim, D., Kaucher, A., Oatley, M. J. & Oatley, J. M. CXCL12-CXCR4 signaling is required for the maintenance of mouse spermatogonial stem cells. J. Cell Sci. 126, 1009–1020 (2013).
pubmed: 23239029
pmcid: 4074255
Gilbert, D. C. et al. Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents. J. Pathol. 217, 94–102 (2009).
pubmed: 18839394
doi: 10.1002/path.2436
Fankhauser, C. D. et al. CXCL12 expression is an adverse predictor for disease recurrence in patients with metastatic non-seminomatous testicular germ cell tumors. BMC Cancer 19, 802 (2019).
pubmed: 31412792
pmcid: 6693197
doi: 10.1186/s12885-019-5961-1
Lobo, J., Gillis, A. J. M., van den Berg, A. & Looijenga, L. H. J. Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers. BMC Cancer 20, 728 (2020).
pubmed: 32758242
pmcid: 7405370
doi: 10.1186/s12885-020-07220-6
Datta, M. W., Renshaw, A. A., Dutta, A., Hoffman, M. A. & Loughlin, K. R. Evaluation of cyclin expression in testicular germ cell tumors: cyclin E correlates with tumor type, advanced clinical stage, and pulmonary metastasis. Mod. Pathol. 13, 667–672 (2000).
pubmed: 10874672
doi: 10.1038/modpathol.3880117
Albers, P. et al. MIB-1 immunohistochemistry in clinical stage I nonseminomatous testicular germ cell tumors predicts patients at low risk for metastasis. Cancer 79, 1710–1716 (1997).
pubmed: 9128986
doi: 10.1002/(SICI)1097-0142(19970501)79:9<1710::AID-CNCR11>3.0.CO;2-0
Albers, P. et al. Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors. Mod. Pathol. 8, 492–497 (1995).
pubmed: 7545814
Sanmamed, M. F. et al. Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours. J. Transl. Med. 15, 62 (2017).
pubmed: 28320414
pmcid: 5358043
doi: 10.1186/s12967-017-1162-3
Miyoshi, E., Terao, M. & Kamada, Y. Physiological roles of N-acetylglucosaminyltransferase V(GnT-V) in mice. BMB Rep. 45, 554–559 (2012).
pubmed: 23101508
doi: 10.5483/BMBRep.2012.45.10.190
Kyan, A. et al. Positive expressions of N-acetylglucosaminyltransferase-V (GnT-V) and beta1-6 branching N-linked oligosaccharides in human testicular germ cells diminish during malignant transformation and progression. Int. J. Oncol. 32, 129–134 (2008).
pubmed: 18097551
Hatakeyama, S. et al. Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor. Int. J. Cancer 127, 1052–1059 (2010).
pubmed: 20017138
pmcid: 2897929
doi: 10.1002/ijc.25117
Gagliardi, M., Strazzullo, M. & Matarazzo, M. R. DNMT3B functions: novel insights from human disease. Front. Cell Dev. Biol. 6, 140 (2018).
pubmed: 30406101
pmcid: 6204409
doi: 10.3389/fcell.2018.00140
Arai, E., Nakagawa, T., Wakai-Ushijima, S., Fujimoto, H. & Kanai, Y. DNA methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma. Histopathology 60, E12–E18 (2012).
pubmed: 22394436
pmcid: 3465786
doi: 10.1111/j.1365-2559.2012.04174.x
Moroy, T. & Geisen, C. Cyclin E. Int. J. Biochem. Cell Biol. 36, 1424–1439 (2004).
pubmed: 15147722
doi: 10.1016/j.biocel.2003.12.005
Furusato, B., Mohamed, A., Uhlen, M. & Rhim, J. S. CXCR4 and cancer. Pathol. Int. 60, 497–505 (2010).
pubmed: 20594270
doi: 10.1111/j.1440-1827.2010.02548.x
Martinet, L. et al. Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res. 71, 5678–5687 (2011).
pubmed: 21846823
doi: 10.1158/0008-5472.CAN-11-0431
Okayama, H. et al. Ectopic expression of MECA-79 as a novel prognostic indicator in gastric cancer. Cancer Sci. 102, 1088–1094 (2011).
pubmed: 21281400
doi: 10.1111/j.1349-7006.2011.01895.x
Planells-Palop, V. et al. Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis. Mol. Cancer 16, 84 (2017).
pubmed: 28446200
pmcid: 5406905
doi: 10.1186/s12943-017-0653-4
Shang, S., Hua, F. & Hu, Z. W. The regulation of beta-catenin activity and function in cancer: therapeutic opportunities. Oncotarget 8, 33972–33989 (2017).
pubmed: 28430641
pmcid: 5464927
doi: 10.18632/oncotarget.15687
Azam, A. S. et al. Diagnostic concordance and discordance in digital pathology: a systematic review and meta-analysis. J. Clin. Pathol. 74, 448–455 (2021).
pubmed: 32934103
doi: 10.1136/jclinpath-2020-206764
Colling, R. et al. Digital pathology transformation in a supraregional germ cell tumour network. Diagnostics https://doi.org/10.3390/diagnostics11122191 (2021).
doi: 10.3390/diagnostics11122191
pubmed: 34943429
pmcid: 8700654
Lewin, J. et al. Gene expression signatures prognostic for relapse in stage I testicular germ cell tumours. BJU Int. 122, 814–822 (2018).
pubmed: 29726090
doi: 10.1111/bju.14372
Cullen, M. et al. The 111 study: a single-arm, phase 3 trial evaluating one cycle of bleomycin, etoposide, and cisplatin as adjuvant chemotherapy in high-risk, stage 1 nonseminomatous or combined germ cell tumours of the testis. Eur. Urol. 77, 344–351 (2020).
pubmed: 31901440
pmcid: 7026695
doi: 10.1016/j.eururo.2019.11.022
Oliver, R. T. et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet 366, 293–300 (2005).
pubmed: 16039331
doi: 10.1016/S0140-6736(05)66984-X
Groot, H. J. et al. Risk of solid cancer after treatment of testicular germ cell cancer in the platinum era. J. Clin. Oncol. 36, 2504–2513 (2018).
pubmed: 29989856
doi: 10.1200/JCO.2017.77.4174
Westermann, D. H. et al. Long-term followup results of 1 cycle of adjuvant bleomycin, etoposide and cisplatin chemotherapy for high risk clinical stage I nonseminomatous germ cell tumors of the testis. J. Urol. 179, 163–166 (2008).
pubmed: 18001800
doi: 10.1016/j.juro.2007.08.172