Testicular cancer is the most common solid tumor among males 15 to 34 years of age, with an estimated 8,850 new cases and 410 deaths during 2017 in the United States. With effective treatment, the overall five-year survival rate is 97%. The signs and symptoms of testicular cancer include scrotal swelling, scrotal heaviness, painless, solid testicular mass, firmness of the testis, dull ache in the scrotum or abdomen, acute pain in the testis or scrotum. Epididymitis is an important part of the differential diagnosis of a scrotal mass. Epididymitis is an inflammation of the coiled tube (epididymis) at the back of the testicle that stores and carries sperm. If tenderness, swelling, or examination abnormalities persist after antibiotic treatment, further evaluation is necessary to rule out testicular cancer. Individuals with symptoms of metastatic disease (about 5 percent of patients with testicular cancer) may present with a neck mass, abdominal mass, lumbar back pain, cough, hemoptysis, dyspnea, or gastrointestinal symptoms. Approximately 10 percent of men with testicular cancer have gynecomastia from tumors that secrete beta subunit of human chorionic gonadotropin.

Risk factors for testicular cancer are numerous.

• In patients with undescended testis (cryptorchidism), the relative risk of developing testicular cancer ranges from 2.9 to 6.3; the risk is increased in both testes, although the risk is much higher in the ipsilateral (same side) testis. Among these patients, the risk of cancer increases when orchiopexy is delayed until after puberty or never performed compared with early orchiopexy. Orchiopexy describes the operation to surgically correct an undescended testicle to move and/or permanently fix a testicle into the scrotum. Even after early orchiopexy, the risk of testicular cancer remains elevated compared with the general population.
• Patients with a personal history of testicular cancer have a 12-times greater risk of developing a contralateral (opposite side) testicular cancer than the general population. However, the greatest risk is in the first five years after diagnosis, and the 15-year cumulative risk is 1.9%. In addition, patients with a father or brother with testicular cancer have a significantly great risk of developing the disease.
• Moreover, men with infertility have an increased risk of developing testicular cancer, although the underlying mechanism is unclear.
• Associations between testicular cancer and marijuana use, inguinal hernia, diet, maternal smoking, and body size are inconclusive.
• Infections with human papillomavirus (HPV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), parvovirus B-19, and human immunodeficiency virus (HIV) increase an individual’s risk.
• In addition, trauma to the testicle is a risk factor.
• Furthermore, high maternal estrogen levels are also a risk factor.

However, testicular microlithiasis and vasectomy are not risk factors for testicular cancer.

Conventional Therapies

If a solid intratesticular mass is discovered, orchiectomy is both diagnostic and therapeutic. Radical inguinal orchiectomy is a surgical procedure in which one or both testicles are removed, including removal of the spermatic cord to the internal inguinal ring. It is the primary treatment for any malignant tumor found on surgical exploration of a testicular mass. Testis-sparing surgery is generally not recommended but may be performed for a small tumor in one testis or for small bilateral tumors. Orchiectomy may be delayed if life-threatening metastases require more urgent attention. Treatment after orchiectomy is based on histology, staging, prognosis, and an individualized discussion with the patient on the benefits and risks of treatment options. Additional therapies may include radiation and/or chemotherapy.

The high survival rate and young age of patients with testicular cancer result in long periods of survivorship with multiple sources of potential morbidity and mortality. Complications arise from both the disease process and treatment and vary according to each individual.

Secondary malignancy may be a concern in these individuals. Testicular cancer survivors treated with radiotherapy or chemotherapy are at increased risk of secondary malignant neoplasms. There is a threefold increased risk of leukemia among testicular cancer survivors treated with radiotherapy to the abdomen and pelvis. Cisplatin and etoposide therapies also increase the risk of secondary leukemia. Radiotherapy and chemotherapy increase the risk of solid cancers beginning five years after treatment. Sites of secondary malignancy included stomach, pancreas, pleura, bladder, colon, and esophagus.

Infertility and hypogonadism should be addressed. Cancer alone may affect fertility. A systematic review found that up to 50% of patients with testicular cancer have semen abnormalities prior to orchiectomy. Orchiectomy and the effects of chemotherapy and radiation also carry significant risks of future infertility. Retrograde ejaculation (when the semen travels backwards into the bladder) or anejaculation (inability to ejaculate) may occur but advances in surgical techniques have reduced this risk.

Adjuvant therapy increases the short- and long-term risks of cardiovascular disease in testicular cancer survivors. A recent population-based study of more than 15,000 testicular cancer survivors found a fivefold increased risk of cardiovascular mortality within the first year after chemotherapy compared with orchiectomy alone. This cardiovascular risk was not significant beyond the first year. A retrospective study of testicular cancer survivors compared with age-matched control patients showed that radiotherapy or chemotherapy imposes greater than a twofold increased long-term risk (after 10 years posttreatment) for atherosclerotic heart disease; combined therapy increased the risk to almost fivefold. Mediastinal irradiation carries more risk than subphrenic irradiation. There are no evidence-based recommendations for heart disease screening in testicular cancer survivors. Patients and their health care providers should be aware of potential cardiovascular risk in testicular cancer survivors.

Precision Medicine Therapies

Precision medicine therapies include all the conventional approaches discussed previously along with the following treatments.

Smoking. Stop smoking! Smoking cessation therapies have been shown to be helpful for many people.

Stress. Stress from any cause is known to modify the immune response and can partially suppress certain aspects of immune function. In addition, prolonged psychological stress appears to be correlated with cellular aging, inducing characteristic senescence features such as increased oxidative stress, reduced telomere length, chronic exposure to glucocorticoids, decreased thymus, changes in cell trafficking, decreased cell-mediated immune response, steroid resistance, and chronic low-grade inflammation. In fact, immunosenescence (alteration of immune function due to aging) has been widely reported in older individuals, as a result of the chronic antigen stimulation and cellular stress encountered throughout life. Furthermore, both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system in testicular cancer survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases.

The increasing evidence described above that some cancer treatments may induce cellular senescence and aging of the immune system, may have implications on the development of secondary medical conditions later in life. Testicular cancer survivors have an increased risk of suffering late adverse events, including hypogonadism, infertility, metabolic syndromes, neurotoxicity, lower cognitive functions, reduced renal function, heart disease, and secondary cancers. Hypogonadism also increases the risk of developing metabolic syndrome, including cardiovascular complications and diabetes, which appears to be greater after combination therapy (chemo-radiotherapy). In addition, testicular cancer survivors struggle with high rates of anxiety and post-traumatic stress disorder (PTSD).

Inflammation. One study hypothesized a correlation between low testosterone levels and increased secretion of pro-inflammatory cytokines as the cause and maintenance of chronic diseases. The inflammatory component in the body can be lowered with EPA/DHA (fish oil) and curcumin. Compounded prescription low-dose naltrexone is also a fabulous anti-inflammatory agent, and it also has other positive anti-cancer effects.

Low-Dose Naltrexone (LDN). The results of increasing studies indicate that LDN exerts its immunoregulatory activity by binding to opioid receptors in or on immune cells and tumor cells. Consequently, these new discoveries indicate that LDN is a promising immunomodulatory agent in the therapy for cancer and many immune-related diseases. It has also been reported that LDN is able to reduce tumor growth by interfering with cell signaling as well as by modifying the immune system. This data supports further the idea that LDN possesses anticancer activity.

Testosterone Replacement. A recent study is the first to investigate the effect of testosterone replacement in testicular cancer survivors with mild Leydig cell insufficiency. Increasing testosterone levels decreases the risk of developing other long-term diseases such as hypercholesterolemia, insulin resistance, diabetes, metabolic syndrome, weight gain, and sexual dysfunction.

Conclusion

As you have seen there are both conventional and precision/anti-aging medicine treatments that are successful for testicular cancer. The increasing evidence that some cancer treatments may induce cellular senescence and aging of the immune system may have implications on the development of secondary medical conditions later in life. Testicular cancer survivors have an increased risk of suffering late adverse events, including hypogonadism (when the testes produce little or no hormones), infertility, metabolic syndromes, neurotoxicity, lower cognitive functions, reduced renal function, heart disease, and secondary cancers. Hypogonadism also increases a person’s risk of developing metabolic syndrome, including cardiovascular complications and diabetes, which appears to be greater after combination therapy (chemo-radiotherapy). In addition, testicular cancer survivors struggle with high rates of anxiety and post-traumatic stress disorder (PTSD). Many of these disease processes can be mitigated by a precision medicine approach to healthcare.

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