Colorectal cancer

Although colorectal cancer is uncommon in young adults, its incidence is rising in the last decades. This trend is discordant with that one regarding older adults, who benefit from screening programs. Around 10% of colorectal cancers are diagnosed in patients below the age of 50 years, and when considering distant colon and rectal lesions the incidence at younger age is even higher, representing more than 40% of cases (1).

Colorectal cancer is more commonly associated with a familial cancer syndrome, including the presence of a known inherited cancer syndrome or a family history. The most common is Lynch syndrome, an autosomal dominant inherited cancer syndrome caused by pathogenic variants of DNA mismatch repair system genes like MLH1, MLH2, MLH6 and PMS2. It is characterized by the development of colorectal, endometrial, ovarian cancers and other less common neoplastic lesions. This multiorgan presentation involving uterus and the ovaries, and the rare incidence of this syndrome make it hard to achieve consensus about the best fertility sparing approach for patients with Lynch syndrome, since its effectiveness and safety are not yet proven (2). 

The treatment of early-stage disease is radical surgery involving the removal of the tumor and draining lymph nodes. Adjuvant radiotherapy is usually added to reduce the risk of local recurrence. Adjuvant chemotherapy is advisable in case of increased risk of recurrence, like in stage 2 and 3, and is more likely to be offered to younger patients (3).  

Young female patients diagnosed with colorectal cancers may experience infertility issues later in life for a number of reasons, including iatrogenic damage following pelvic surgery, pelvic radiation and chemotherapy (4,5). 

Fertility may be impaired by pelvic surgery like ilea-pouch-anal anastomosis, mainly due to postoperative adhesions leading to fallopian tube obstruction (4). The ovarian reserve may be also injured by adjuvant treatments following surgery. Indeed, pelvic radiations are detrimental for the ovaries depending on age, dose and field of radiation (6). Moreover, chemotherapy may be detrimental as well. In colorectal cancer, it usually involves the use of 5FU, has not been evidenced as gonadotoxic, and oxaliplatin, which on the contrary has a detrimental effect on the ovarian reserve although less than other drugs from the same family (7), plus biologic agents (bevacizumab, cetuximab, panitumumab) for which the gonadotoxic risk has not been completely assessed. 

Young patients have to be informed about their increased risk of infertility due to cancer treatments and their fertility preservation options. Fertility preservation options include oocyte cryopreservation, embryo cryopreservation and ovarian tissue preservation. 

Ovarian cortical strip freezing can be performed in case of macroscopically normal ovaries. The risk of minimal residual disease within the cryopreserved ovarian tissue may range between 0 and 8 %, according to the literature. Colorectal cancer may involve the ovaries by four possible routes, meaning transcoelomic, hematologeneous, lymphatic or direct, being therefore not necessarily related to the most advanced stages. Moreover, ovarian metastases may be visible on the surface of be deep inside the organs, and they are encountered to be microscopical in around 50% of cases. For this reason, it is difficult to determine which patients have the highest risk (8). Preliminary tests involving immunolabeling and molecular biology techniques need to be conducted before ovarian tissue transplantation in all colorectal cancer survivors, to rule out the risk of reimplanting malignant cells within ovarian tissue. 

References:

1. Levine O, Zbuk K. Colorectal cancer in adolescents and young adults: Defining a growing threat. Pediatr Blood Cancer. 2019 Nov;66(11):e27941.
2. Corrado G, Marchetti C, Trozzi R, Scambia G, Fagotti A. Fertility preservation in patients with BRCA mutations or Lynch syndrome. Int J Gynecol Cancer. 2021 Mar;31(3):332-338.
3. Hubbard JM, Grothey A. Adolescent and young adult colorectal cancer. J Natl Compr Canc Netw. 2013 Oct 1;11(10):1219-25.
4. Spanos CP, Mamopoulos A, Tsapas A, Syrakos T, Kiskinis D. Female fertility and colorectal cancer. Int J Colorectal Dis. 2008 Aug;23(8):735-43.
5. Letourneau JM, Ebbel EE, Katz PP, Oktay KH, McCulloch CE, Ai WZ, Chien AJ, Melisko ME, Cedars MI, Rosen MP. Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer. Cancer. 2012 Apr 1;118(7):1933-9.
6. Wallace WH, Thomson AB, Kelsey TW. The radiosensitivity of the human oocyte. Hum Reprod. 2003 Jan;18(1):117-21.
7. Levi M, Shalgi R, Brenner B, Perl G, Purim O, Amit L, Stemmer SM, Ben-Aharon I. The impact of oxaliplatin on the gonads: from bedside to the bench. Mol Hum Reprod. 2015 Dec;21(12):885-93.
8. Pitt J, Dawson PM. Oophorectomy in women with colorectal cancer. Eur J Surg Oncol. 1999 Aug;25(4):432-8.