What are testes and what is their Anatomy?
Testes (singular: testis or testicle) are paired, oval-shaped, male-reproductive glands, which sit in the scrotum (supporting structure for the testes which hangs beneath the base of the penis) and measure about 5 cm in length and 2.5 cm in diameter.
They normally develop in the abdomen and descend into the scrotum through the inguinal canals during the seventh month of fetus development. The main function of the testes is to produce sperms and the male hormones (androgens) such as testosterone.
What are the types of Testicular Cancers?
The testes are made up of mainly 3 types of cells: spermatogenic cells (germ cells), Sertoli cells, and interstitial (or Leydig) cells. Each of these cells can develop into one or more types of cancer. Germ cell tumors are the most commonly encountered (around 90-95% of all cases) testicular cancer.
Germ cell tumors are classified into following 2 types based on the type of cells involved, growth rate, and type of treatment approach usually followed for such tumors:
- Embronal Carcinoma
- Endodermal Sinus/Yolk Sac Tumors
Testicular Cancer Risk Factors
Cryptorchidism, or failure of descent of the testis into the scrotal sac, is also a risk factor for the disease. In this condition, testis may lie either in the abdomen or in the inguinal canal, as you can see in the figure.
Race and Ethnicity
The risk of testicular cancer is around 4 to 5 times higher in white men living in the United States and Europe compared to that of black men living in Africa or Asia. The incidence of testicular cancer is highest in North-European and least in Asians and Africans. However, the reason for this difference in incidence is unknown.
Individuals with a personal history of testicular are generally at higher risk of developing second cancer in another testicle. Previous history of cancer in the opposite testis, previous testicular biopsy, testicular atrophy or impaired fertility also increase the testicular cancer risk factor.
Risk of developing testicular cancer increases in an individual with a history of testicular cancer in close relatives.
Genetic Cancer Predisposition Syndromes
Various syndromes such as Down’s syndrome. Klinefelter’s syndrome and testicular dysgenesis syndrome may also be a risk factor for the disease.
- Down’s Syndrome (caused due to defect in chromosome 21);
- Klinefelter’s syndrome (caused due to the presence of two or more X chromosomes in males);
- Testicular dysgenesis, and
- Testicular feminization syndrome.
Infection with human immunodeficiency virus (HIV) is associated with an increased risk of testicular cancer.
Abnormal development of testicles, testicular atrophy due to injury, orchitis, and exposure to radiation in past is associated with increased level of follicle-stimulating hormone (FSH) which is postulated to increase the risk of testicular cancer.
Obese and tall men are also considered to be at increased risk of developing testicular cancer.
Symptoms and Signs of Testicular Cancer
Symptoms may be due to local or distant spread.
Local spread may cause:
- Painless testicular swelling
- Change in how testicles feel
- Ache in the lower abdomen.
Distant spread may cause:
- Cough, breathlessness
- Bone pain
Other symptoms of testicular cancer may depend on the site of metastasis. Most common sites of spread of testicular cancer are liver, lung and bone.
Testicular Cancer Staging Investigations
Ultrasound of the scrotum is generally the first test performed when testicular cancer is suspected. It helps us to differentiate whether the mass is intra-testicular or extra-testicular, that is, whether it is inside or outside the testis. Then we have to see whether it is solid or cystic. A solid, intratesticular mass goes in the favor of testicular cancer.
This helps the doctor to examine both the testes along with the nearby structures for any abnormal areas. This test can distinguish testicular cancer from non-cancerous conditions such as testicular torsion, hydrocele, varicocele, spermatocele, and epididymitis.
Blood tests for tumor markers
Human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are common tumor markers for testicular cancer. Assessment of levels of these markers is very useful in testicular cancer as the blood level of these markers convey useful information concerning diagnosis, staging, prognosis (course of a medical condition), disease progression/recurrence, and response to treatment.
Beta HCG (Human Chorionic Gonadotropin)
HCG is a glycoprotein consisting of 2 subunits – alpha and beta. HCG level in blood is generally measured with the help of beta-subunit. An elevated level of HCG is usually associated with embryonal carcinoma, choriocarcinoma, and seminoma. Extremely high level of HCG is generally detected in choriocarcinoma. However, an increase in the level of HCG can also be seen in other cancer types such as prostate, bladder, ureteral, renal cancer, etc.
AFP (Alpha Feto Protein)
An elevated level of AFP is usually associated with embryonal carcinoma and yolk sac tumors. Seminomas and choriocarcinoma do not increase the level of AFP. However, increased level of AFP may also be found in patients with hepatocellular carcinoma, liver cirrhosis, hepatitis, etc.
LDH (Lactate Dehydrogenase)
LDH is an enzyme which helps in energy production and normally found in almost all body tissues. An elevated level of LDH is generally associated with the tissue damage. In patients with testicular cancer, it is usually related to tumor burden, disease prognosis, and indicates the response to treatment.
So after doing testicular ultrasound and tumor markers, the next step is systemic imaging. This helps us to diagnose the spread of the disease to other part of the body. For systemic imaging, we require the CT scan of abdomen, pelvis and thorax. Very rarely, we may require MRI brain or bone scan to look for the spread of the disease to brain or bones.
- Computed tomography (CT) scan
- Positron emission tomography (PET) scan
- Magnetic resonance imaging (MRI) Scan
High Inguinal orchiectomy
Stages of Testicular Cancer
Before discussing the staging, let’s have a look at the anatomy of human testis. This will help to understand staging better.
Testis is the rounded structure, that produces sperm and testosterone.
The duct joining the testis is called as vas deferens.
In front of the testis lies the penis, through which urethra passes. It is connected superiorly to the urinary bladder and helps in passing the urine.
At the upper part is epidydimis, which joins the vas deferens superiorly.
The covering outside the testis is called as spermatic cord. It is composed of three layers, internal and external spermatic fascia and cremasteric muscle. And the outermost pouch like covering that holds both the testis is called a scrotum.
TNM is the most commonly used system for staging testicular cancer. “T” stands for “Tumor Size”, “N” for “Lymph Nodes”, “M” for “Metastasis”, and “S” stands for “Serum level of tumor markers”.
Tis – The cancer cells are present only in the seminiferous tubules (small tube-like structures inside the testes).
T1 – Tumor limited to testis/epididymis and has invaded up to the tunica albuginea but has not grown into tunica vaginalis or nearby blood vessels/lymphatics. T2 – Tumor limited to testis/epididymis and has invaded up to the tunica vaginalis or blood vessels/lymphatics involvement by the tumor. T3 – Tumor has invaded the spermatic cord with or without blood vessels/lymphatics involvement. T4 – Tumor has invaded the scrotum with or without blood vessels/lymphatics involvement.
So after the T staging, comes the N staging or the nodal staging. The absence of regional lymph nodes is called as N0, whereas, the involvement of regional lymph nodes is called as N1, N2 or N3 depending upon the size and the number of the nodes.
These nodal structures called retroperitoneal lymph nodes are the regional lymph nodes for testicular cancer. Their size and number determine the N-stage, that is N1, N2 or N3.
N0 – No spread to regional lymph nodes
N1 – Tumor spread to single or multiple regional lymph node(s) none >2 cm in greatest dimension
N2 – Tumor spread to single or multiple regional lymph node(s), any one >2 cm but </=5 cm in greatest dimension
N3 – Tumor spread to lymph node mass >5 cm in greatest dimension
After the T and N staging, comes the M staging for testicular cancer.
It is called as M1a if there is spread to non-regional lymph nodes, that is, any nodes except retroperitoneal lymph nodes as discussed above, or if there is spread to lungs that are called as pulmonary metastasis.
Whereas spread to the organs than lungs is called as M1b.
Similarly, the involvement of inguinal lymph nodes is also M1a disease because it is a non-regional lymph node for testis. And here, the involvement of supraclavicular lymph node is non-regional. M1a disease also includes the cases with pulmonary metastasis, that is spread of the tumor to lungs. M1b – Whereas, spread to the organs of the body other than lung is called as M1b. In this figure spread to liver makes it M1b.
Spread to brain or bones is also M1b.
Testicular Tumor Serum Marker Levels
- LDH <1.5 times the upper limit of the normal (ULN) range,
- beta-hCG < 5,000 mIu/mL, and/or
- AFP < 1,000 ng/mL.
- LDH is 1.5 to 10 times the ULN
- beta-hCG is 5,000 to 50,000 mIu/mL, and/or
- AFP is 1,000 to 10,000 ng/mL.
- LDH > 10 times the ULN
- beta-hCG > 50,000 mIu/mL, and/or
- AFP > 10,000 ng/mL.
3 Stages of Testicular Germ Cell Tumors
Once T, N, M, and S categories are determined through different diagnostic techniques, this information is combined to assign an overall stage (from 0 to IV) to the disease.
|0||Tis N0 M0 S0|
|IA||T1 N0 M0 S0|
|IB||T2 N0 M0 S0|
|T3 N0 M0 S0|
|T4 N0 M0 S0|
|IS||Any T N0 M0 S1-3|
|IIA||Any T N1 M0 S0-1|
|IIB||Any T N2 M0 S0-1|
|IIC||Any T N3 M0 S0-1|
|IIIA||Any T Any N M1a S0-1|
|IIIB||Any T N1-3 M0 S2|
|Any T Any N M1a S2|
|IIIC||Any T N1-3 M0 S3|
|Any T Any N M1a S3|
|Any T Any N M1b Any S|
What is Stage 3 Disease? Is it Curable?
Stage 3 includes cases of testicular cancer that has spread to non-regional lymph nodes (other than retroperitoneal lymph nodes) like mediastinal, supraclavicular, inguinal, etc. Also, it includes cases with spread to distant sites like lungs, brain, liver, bones, etc. Also, the cases with serum tumor marker levels in S2 or S3 range (discussed above) are classified as stage 3. Stage 3 testicular cancer is definitely curable, with 5 year survival rate of around 80%.
What is Stage 4 Disease?
As you can see in the stage grouping above, there is no stage 4 in testicular cancer. Involvement of non-regional lymph nodes and/or distant metastasis is classified as Stage 3, unlike other cancers where it is stage 4.
Treatment of Testicular Germ Cell Tumor
The testicular cancer treatment depends on the type of testicular cancer (seminoma versus non-seminoma), stage of the disease, performance status of the patient, along with other factors.
Treatment of Seminoma Testis
Stage 0Tis N0 M0 S0 Surveillance is generally preferred approach for patients with Stage 0 seminomas. The patient should be screened frequently for any sign of disease progression. No other treatment is generally recommended.
Stage IT1-4 N0 M0 Sx
Stage IIAny T N1-3 M0 Sx
Stage IIIAny T Any N M1 Sx
Treatment of Non-Seminoma Testis
Stage 0Tis N0 M0 S0
Stage IT1-4 N0 M0 Sx
Stage IIAny T N1-3 M0 Sx
Stage IIIAny T Any N M1 Sx
Surgery for Testicular Cancer
Mainly 2 types of surgeries are performed for testicular cancer treatment: High inguinal orchiectomy and retroperitoneal lymph node dissection (RPLND).
In high inguinal orchiectomy, the affected testicle, spermatic cord, and associated blood and lymph vessels (that can provide passage for cancer spread) are removed.
In RPLND, the cancer-containing lymph nodes in the abdomen (known as retroperitoneal lymph nodes surrounding the aorta and inferior vena cava) are removed. RPLND can be performed as an open surgery or as a laparoscopic procedure. Also, some patients may opt for sperm banking for fertility preservation before the surgery.
Chemotherapy for Testicular Cancer
Testicular cancer is one of the most chemoresponsive tumor. Indications of chemotherapy in seminoma and non-seminoma are discussed above.
Some chemotherapy drugs that are a part of testicular cancer treatment regimens are-
Best Testicular Cancer (Germ Cell Tumor) Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating testicular cancer patients with chemotherapy. He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Tumor Markers- AFP, Beta HCG, LDH, High Inguinal Orchidectomy, CT Guided Biopsy, etc. Other treatment facilities for Testicular Cancer available are Retroperitoneal Lymph Node Dissection, Radical Inguinal Orchidectomy, Laproscopic Sugery, Radiation Therapy, etc.
Call +91 9686813020 for appointment.