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24-03-2023 | Prostate Cancer | Topic Paper

Gender-specific counselling of patients with upper tract urothelial carcinoma and Lynch syndrome

Authors: Clara Cerrato, Savio Domenico Pandolfo, Riccardo Autorino, Andrea Panunzio, Alessandro Tafuri, Antonio Benito Porcaro, Alessandro Veccia, Vincenzo De Marco, Maria Angela Cerruto, Alessandro Antonelli, Ithaar H. Derweesh, Maria Carmen Mir Maresma

Published in: World Journal of Urology | Issue 7/2023

Abstract

Purpose

Lynch syndrome (LS) is an autosomal dominant genetic syndrome resulting in a wide spectrum of malignancies caused by germline mutations in mismatch repair genes (MMR). Gene mutations have different effects and penetrance between the two genders. The aim of this review is to offer a gender-specific evidence-based clinical guide on diagnosis, screening, surveillance, and counselling of UTUC patients with LS.

Methods

Using MEDLINE, a non-systematic review was performed including articles between 2004 and 2022. English language original articles, reviews, and editorials were selected based on their clinical relevance.

Results

Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Up to 21% of new UTUC cases may have unrecognized LS as the underlying cause. LS-UTUC does not have a clear gender prevalence, even if it seems to slightly prefer the male gender. The MSH6 variant is significantly associated with female gender (p < 0.001) and with gynecological malignancies. Female MSH2 and MLH1 carriers have higher rates for endometrial and ovarian cancer with respect to the general population, while male MSH2 and MLH1 carriers have, respectively, higher rate of prostate cancer and upper GI tract, or biliary or pancreatic cancers. Conflicting evidence remains on the association of testicular cancer with LS.

Conclusion

LS is a polyhedric disease, having a great impact on patients and their families that requires a multidisciplinary approach. UTUC patients should be systematically screened for LS, and urologists have to be aware that the same MMR mutation may lead to different malignancies according to the patient’s gender.

Bucksch K, Zachariae S, Aretz S et al (2020) Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study. BMC Cancer 20:460. https://doi.org/10.1186/s12885-020-06926-xCrossRefPubMedPubMedCentral

Dominguez-Valentin M, Sampson JR, Seppälä TT et al (2020) Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med 22:15–25. https://doi.org/10.1038/s41436-019-0596-9CrossRefPubMed

Roupret M, Catto J, Coulet F et al (2004) Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cell carcinoma. J Med Genet 41:e91. https://doi.org/10.1136/jmg.2003.017871CrossRefPubMedPubMedCentral

Bonis PA, Trikalinos TA, Chung M et al (2007) Hereditary nonpolyposis colorectal cancer: diagnostic strategies and their implications. Evid Rep Technol Assess (Full Rep) 150:1–180

Watson P, Vasen HFA, Mecklin JP et al (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123:444–449. https://doi.org/10.1002/ijc.23508CrossRefPubMedPubMedCentral

Ju JY, Mills AM, Mahadevan MS et al (2018) Universal Lynch syndrome screening should be performed in all upper tract urothelial carcinomas. Am J Surg Pathol 42:1549–1555. https://doi.org/10.1097/PAS.0000000000001141CrossRefPubMed

Rouprêt M, Yates DR, Comperat E, Cussenot O (2008) Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (Lynch syndrome) tumor spectrum. Eur Urol 54:1226–1236. https://doi.org/10.1016/j.eururo.2008.08.008CrossRefPubMed

Barrow PJ, Ingham S, O’Hara C et al (2013) The spectrum of urological malignancy in Lynch syndrome. Fam Cancer 12:57–63. https://doi.org/10.1007/s10689-012-9573-zCrossRefPubMed

Pradere B, Lotan Y, Roupret M (2017) Lynch syndrome in upper tract urothelial carcinoma: significance, screening, and surveillance. Curr Opin Urol 27:48–55. https://doi.org/10.1097/MOU.0000000000000340CrossRefPubMed

10.

Audenet F, Colin P, Yates DR et al (2012) A proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis: proposal of patient-specific risk identification tool. BJU Int 110:E584-589. https://doi.org/10.1111/j.1464-410X.2012.11298.xCrossRef

11.

Metcalfe MJ, Petros FG, Rao P et al (2018) Universal point of care testing for Lynch syndrome in patients with upper tract urothelial carcinoma. J Urol 199:60–65. https://doi.org/10.1016/j.juro.2017.08.002CrossRefPubMed

12.

Marabelle A, Le DT, Ascierto PA et al (2020) Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 38:1–10. https://doi.org/10.1200/JCO.19.02105CrossRefPubMed

13.

Olivier R, Randrian V, Tougeron D, Saurin JC (2021) Endoscopy to diagnose and prevent digestive cancers in Lynch syndrome. Cancers (Basel) 13:3505. https://doi.org/10.3390/cancers13143505CrossRefPubMedPubMedCentral

14.

Donahue TF, Bagrodia A, Audenet F et al (2018) Genomic characterization of upper-tract urothelial carcinoma in patients with Lynch syndrome. JCO Precis Oncol. https://doi.org/10.1200/PO.17.00143CrossRefPubMedCentral

15.

Harper HL, McKenney JK, Heald B et al (2017) Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and Lynch syndrome. Mod Pathol 30:146–156. https://doi.org/10.1038/modpathol.2016.171CrossRefPubMed

16.

Lonati C, Necchi A, Gómez Rivas J et al (2022) Upper tract urothelial carcinoma in the Lynch syndrome tumour spectrum: a comprehensive overview from the European Association of Urology–Young Academic Urologists and the Global Society of Rare Genitourinary Tumors. Eur Urol Oncol 5:30–41. https://doi.org/10.1016/j.euo.2021.11.001CrossRefPubMed

17.

Joost P, Therkildsen C, Dominguez-Valentin M et al (2015) Urinary tract cancer in Lynch syndrome; increased risk in carriers of MSH2 mutations. Urology 86:1212–1217. https://doi.org/10.1016/j.urology.2015.08.018CrossRefPubMed

18.

van der Post RS, Kiemeney LA, Ligtenberg MJL et al (2010) Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet 47:464–470. https://doi.org/10.1136/jmg.2010.076992CrossRefPubMed

19.

Crockett DG, Wagner DG, Holmng S et al (2011) Upper urinary tract carcinoma in Lynch syndrome cases. J Urol 185:1627–1630. https://doi.org/10.1016/j.juro.2010.12.102CrossRefPubMed

20.

Hubosky SG, Boman BM, Charles S et al (2013) Ureteroscopic management of upper tract urothelial carcinoma (UTUC) in patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). BJU Int 112:813–819. https://doi.org/10.1111/bju.12008CrossRefPubMed

21.

Therkildsen C, Eriksson P, Höglund M et al (2018) Molecular subtype classification of urothelial carcinoma in Lynch syndrome. Mol Oncol 12:1286–1295. https://doi.org/10.1002/1878-0261.12325CrossRefPubMedPubMedCentral

22.

Soria F, Shariat SF, Lerner SP et al (2017) Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC). World J Urol 35:379–387. https://doi.org/10.1007/s00345-016-1928-xCrossRefPubMed

23.

(2014) ACOG Practice Bulletin No. 147: Lynch syndrome. Obstet Gynecol 124:1042–1054. https://doi.org/10.1097/01.AOG.0000456325.50739.72

24.

Meyer LA, Broaddus RR, Lu KH (2009) Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control 16:14–22. https://doi.org/10.1177/107327480901600103CrossRefPubMed

25.

Liu YL, Breen K, Catchings A et al (2022) Risk-reducing bilateral salpingo-oophorectomy for ovarian cancer: a review and clinical guide for hereditary predisposition genes. JCO Oncol Pract 18:201–209. https://doi.org/10.1200/OP.21.00382CrossRefPubMed

26.

Patel AP, Wang M, Fahed AC et al (2020) Association of rare pathogenic DNA variants for familial hypercholesterolemia, hereditary breast and ovarian cancer syndrome, and Lynch syndrome with disease risk in adults according to family history. JAMA Netw Open 3:e203959. https://doi.org/10.1001/jamanetworkopen.2020.3959CrossRefPubMedPubMedCentral

27.

Win AK, Young JP, Lindor NM et al (2012) Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol 30:958–964. https://doi.org/10.1200/JCO.2011.39.5590CrossRefPubMedPubMedCentral

28.

Grindedal EM, Møller P, Eeles R et al (2009) Germ-line mutations in mismatch repair genes associated with prostate cancer. Cancer Epidemiol Biomarkers Prev 18:2460–2467. https://doi.org/10.1158/1055-9965.EPI-09-0058CrossRefPubMed

29.

Guedes LB, Antonarakis ES, Schweizer MT et al (2017) MSH2 loss in primary prostate cancer. Clin Cancer Res 23:6863–6874. https://doi.org/10.1158/1078-0432.CCR-17-0955CrossRefPubMedPubMedCentral

30.

Lobo J, Pinto C, Pinheiro M et al (2020) Widening the spectrum of Lynch syndrome: first report of testicular seminoma attributable to MSH2 loss. Histopathology 76:486–489. https://doi.org/10.1111/his.13979CrossRefPubMed

31.

Huang D, Matin SF, Lawrentschuk N, Roupret M (2018) Systematic review: an update on the spectrum of urological malignancies in Lynch syndrome. Bladder Cancer 4:261–268. https://doi.org/10.3233/BLC-180180CrossRefPubMedPubMedCentral

32.

Mayer F, Wermann H, Albers P et al (2011) Histopathological and molecular features of late relapses in non-seminomas. BJU Int 107:936–943. https://doi.org/10.1111/j.1464-410X.2010.09631.xCrossRefPubMed

33.

Velasco A, Corvalan A, Wistuba II et al (2008) Mismatch repair expression in testicular cancer predicts recurrence and survival. Int J Cancer 122:1774–1777. https://doi.org/10.1002/ijc.23291CrossRefPubMed

34.

Velasco A, Riquelme E, Schultz M et al (2004) Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence. Cancer Biol Ther 3:1152–1158. https://doi.org/10.4161/cbt.3.11.1218CrossRefPubMed

35.

Honecker F, Wermann H, Mayer F et al (2009) Microsatellite instability, mismatch repair deficiency, and BRAF mutation in treatment-resistant germ cell tumors. J Clin Oncol 27:2129–2136. https://doi.org/10.1200/JCO.2008.18.8623CrossRefPubMed

36.

Vladušić T, Hrašćan R, Krušlin B et al (2014) Histological groups of human postpubertal testicular germ cell tumours harbour different genetic alterations. Anticancer Res 34:4005–4012PubMed

37.

Olasz J, Mándoky L, Géczi L et al (2005) Influence of hMLH1 methylation, mismatch repair deficiency and microsatellite instability on chemoresistance of testicular germ-cell tumors. Anticancer Res 25:4319–4324PubMed

38.

Cárcano FM, Lengert AH, Vidal DO et al (2016) Absence of microsatellite instability and BRAF (V600E) mutation in testicular germ cell tumors. Andrology 4:866–872. https://doi.org/10.1111/andr.12200CrossRefPubMed

39.

Vasen HFA, Mecklin JP, Meera Khan P, Lynch HT (1991) The international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum 34:424–425. https://doi.org/10.1007/BF02053699CrossRefPubMed

40.

Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268. https://doi.org/10.1093/jnci/djh034CrossRefPubMed

41.

Piñol V, Castells A, Andreu M et al (2005) Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA 293:1986–1994. https://doi.org/10.1001/jama.293.16.1986CrossRefPubMed

42.

Lindner AK, Schachtner G, Tulchiner G et al (2021) Lynch syndrome: its impact on urothelial carcinoma. Int J Mol Sci 22:531. https://doi.org/10.3390/ijms22020531CrossRefPubMedPubMedCentral

43.

Leclerc J, Vermaut C, Buisine MP (2021) Diagnosis of Lynch syndrome and strategies to distinguish Lynch-related tumors from sporadic MSI/DMMR tumors. Cancers (Basel) 13:467. https://doi.org/10.3390/cancers13030467CrossRefPubMed

44.

Rouprêt M, Babjuk M, Burger M et al (2020) European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol 79:62–79. https://doi.org/10.1016/j.eururo.2020.05.042CrossRefPubMed

45.

Aarnio M, Säily M, Juhola M et al (2012) Uroepithelial and kidney carcinoma in Lynch syndrome. Fam Cancer 11:395–401. https://doi.org/10.1007/s10689-012-9526-6CrossRefPubMed

46.

Tafuri A, Odorizzi K, di Filippo G et al (2021) Acute kidney injury strongly influences renal function after radical nephroureterectomy for upper tract urothelial carcinoma: a single-centre experience. Arch Ital Urol Androl 93:9–14. https://doi.org/10.4081/aiua.2021.1.9CrossRefPubMed

47.

Tafuri A, Marchioni M, Cerrato C et al (2022) Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium). World J Urol 40:2771–2779. https://doi.org/10.1007/s00345-022-04156-3CrossRefPubMedPubMedCentral

48.

Loizzo D, Pandolfo SD, del Giudice F et al (2022) Ureteroscopy and tailored treatment of upper tract urothelial cancer: recent advances and unmet needs. BJU Int 130:35–37. https://doi.org/10.1111/bju.15746CrossRefPubMed

49.

Rosenberg JE, Hoffman-Censits J, Powles T et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920. https://doi.org/10.1016/S0140-6736(16)00561-4CrossRefPubMedPubMedCentral

50.

Yates DR, Catto JWF (2013) Distinct patterns and behaviour of urothelial carcinoma with respect to anatomical location: How molecular biomarkers can augment clinico-pathological predictors in upper urinary tract tumours. World J Urol 3:21–29. https://doi.org/10.1007/s00345-012-0946-6CrossRef

51.

Califano G, Ouzaid I, Verze P et al (2021) Immune checkpoint inhibition in upper tract urothelial carcinoma. World J Urol 39:1357–1367. https://doi.org/10.1007/s00345-020-03502-7CrossRefPubMed

52.

Møller P, Seppälä TT, Bernstein I et al (2018) Cancer risk and survival in path-MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 67:1306–1316. https://doi.org/10.1136/gutjnl-2017-314057CrossRefPubMed

53.

Gupta S, Weiss JM, Burke CA, et al (2022) NCCN guidelines version 1.2022 genetic/familial high-risk assessment: colorectal continue. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf

54.

Giri VN, Knudsen KE, Kelly WK et al (2018) Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017. J Clin Oncol 36:414–424. https://doi.org/10.1200/JCO.2017.74.1173CrossRefPubMed

55.

Wimmer katharina, Kratz CP, VasenHFA, et al (2014) Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium “Care for CMMRD” (C4CMMRD). J Med Genet 51:355–365. https://doi.org/10.1136/jmedgenet-2014-102284CrossRef

56.

Spencer SJ, Fullerton SM (2022) Population genomic screening: ethical considerations to guide age at implementation. Front Genet 13:899648. https://doi.org/10.3389/fgene.2022.899648CrossRefPubMedPubMedCentral

57.

Fulda KG, Lykens K (2006) Ethical issues in predictive genetic testing: a public health perspective. J Med Ethics 32:143–147. https://doi.org/10.1136/jme.2004.010272CrossRefPubMedPubMedCentral

58.

Brubaker L, Shull B (2015) EGGS for patient-centered outcomes. Int Urogynecol J 16:171–173. https://doi.org/10.1007/s00192-005-1300-yCrossRef

59.

Balzarro M, Rubilotta E, Goss C et al (2018) Counseling in urogynecology: a difficult task, or simply good surgeon—patient communication? Int Urogynecol J 29:943–948. https://doi.org/10.1007/s00192-018-3673-8CrossRefPubMed

60.

Win AK, Dowty JG, Reece JC et al (2021) Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study. Lancet Oncol 22:1014–1022. https://doi.org/10.1016/S1470-2045(21)00189-3CrossRefPubMedCentral

Title: Gender-specific counselling of patients with upper tract urothelial carcinoma and Lynch syndrome
Authors: Clara Cerrato
Savio Domenico Pandolfo
Riccardo Autorino
Andrea Panunzio
Alessandro Tafuri
Antonio Benito Porcaro
Alessandro Veccia
Vincenzo De Marco
Maria Angela Cerruto
Alessandro Antonelli
Ithaar H. Derweesh
Maria Carmen Mir Maresma
Publication date: 24-03-2023
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Prostate Cancer
Urothelial Cancer
Urothelial Cancer
Published in: World Journal of Urology / Issue 7/2023
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-023-04344-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Gender-specific counselling of patients with upper tract urothelial carcinoma and Lynch syndrome

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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