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Taylor A. Johnson
Here at Oncobites, we cover all varieties of cancers, whether they are located in the brain, heart, breast, circulation, or elsewhere. Although we’ve previously discussed ovarian cancer in multiple posts (i.e. Ovarian Cancer and Infections), we have yet to discuss the homologous structure to the ovaries in men; the testes. The testes are fascinating; they house large populations of mixed cell types, all with different phenotypes and functions. Initially, this sounds troublesome, given the variety of cancers that could develop; yet, the survival rates from testicular cancers are extremely high. With this thought in mind, this piece serves to briefly discuss several key considerations pertaining to testicular cancer (A.K.A. the why’s (Y’s) of testicular cancer).
It is important to note that fortunately, testicular cancer is not as common as other cancer types; 1 in every 250 men develop testicular cancer at one point in their life. In addition, the five-year survival rate of testicular cancer is 97% across all races (American Cancer Society). With this in mind, the first “why” question to consider is: Why research testicular cancer if it is rare and the survival rate is high? Unfortunately, testicular cancer is the leading cancer that develops in young-to-middle aged men. Therefore, testicular cancer commonly develops earlier in life than many common forms of cancer. In addition, a critical, and unfortunately overlooked, aspect in patient care is the long-term effects of the cancer and the treatment provided on the patients’ overall quality of life. Considering male fertility, it is well known that testicular cancer is associated with infertility. Approximately 1 in 8 couples are affected by infertility, and men contribute to 50% of the cases. It is worth noting that if a testicle must be removed to treat the patient of the cancer, the other testicle is sufficient enough to produce testosterone and sperm. In addition, fewer than 2% of men develop testicular cancer in both testes, ensuring that most men can retain some fertility after cancer. Collectively, although other cancers may be more common, testicular cancer (if left untreated), could have disastrous long-term effects in men at a very young age.
The next question to consider is: Why (or how) does testicular cancer develop? Imbalances in spermatogenesis (summarized in the image below) , the cellular process that results in sperm production, is one notable cause for cancer development. Starting as spermatogonial stem cells (SSCs), these cells must undergo several divisions (through mitosis and meiosis) in order to generate sperm that are capable of successfully fertilizing an egg. When considering cancer development; a foundational piece is the imbalance growth of a cluster of cells, whether it be due to increased cell proliferation or changes in necessary cell death mechanisms. Given how these germs cells progress through spermatogenesis in a strict step-wise fashion, one can envision how dysregulation at any point in this process could lead to cancer development, as well as infertility.
With this process in mind, one could then answer the question of “Why are there multiple variations of testicular cancer?” Due to the complexity and heterogeneity of the testis, multiple forms of cancer could develop over time. Approximately 90% of testicular cancers arise from different germ cell states. These tumors can take form as seminomas, which develop more commonly in middle-aged adults and are slow spreaders, or as non-seminoma tumors, which develop in the earlier decades of life. Non-seminoma tumors can take for as teratomas or one of multiple carcinomas.
The last, but arguably most important why question, is why do testicular cancer patients have high remission rates compared to other forms of cancer? One explanation is the direct result of the type of cancer that develops. Most testicular cancers that develop are seminomas; cancers that develop in the epithelium of the seminiferous tubule. These are more slow-moving compared to their non-seminoma counterparts. This slow progression not only aids in the detection of the cancer, but also provides clinicians more time to properly treat the condition. A second explanation is that the germ cells within the testis are more sensitive to radiation or chemotherapy compared to other cell types in the body. Earlier this year, a London group showed that a singular treatment of chemotherapy was as effective in preventing testicular cancer remission as multiple rounds of chemotherapy. These are just two proposed responses that may explain this thought-provoking concept.
With these considerations in mind, society as a whole has become more invested in testicular function. On the research front, some areas of interests include the identification of genes up- and down-regulated during cancer development and the design of therapies that are effective and have minimal long-term side effects. At this time, the current approaches (i.e. surgical removal, radiation therapy, chemotherapy) are effective in removing the tumor; however, more work is necessary to identify the cause of the developing tumor. In addition, organizations are designing creative ways to spread advocacy of male reproductive biology. The Testicular Cancer Society, for example, designed an app geared to reminding men to perform monthly check-ups and for providing instructions on self-examinations. Any efforts to increase advocacy are worthwhile, as early detection of these tumors is essential to the removal and/or treatment of the tumor.
Edited by Sara Musetti
Taylor Johnson, M.S. is a doctoral candidate in the Department of Anatomy & Cell Biology at East Carolina University, in Greenville, NC