Testicular Cancer (Germ Cell Tumor) – Risk Factors, Symptoms, Investigations, Staging, Treatment

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testicular cancer image

How a Patient with Test Cancer Presents?

To further understand the disease in a better way, have a look at the video below where CancerBro meets Mr. Tiesto who has recently being diagnosed with testicular cancer. CancerBro asks Mr. Tiesto several important questions related to his disease from SYMPTOMS which lead him to contact an oncologist, to various other risk factors related to testicular cancer.

CancerBro, can you please discuss in detail how the disease presents and what are the risk factors for disease?

Yeah sure, let’s meet Mr. Tiesto.

He is Tiesto, 25 years old boy. One fine day when he got up he incidentally noticed a mass in his right testis. He got very worried and straight away rushed to the hospital. After a series of investigations, he was finally diagnosed as a case of testicular germ cell cancer, let’s meet him.

CancerBro: Hi Mr. Tiesto, how are you feeling today?

Mr. Tiesto: I was very worried for the last few days after I was diagnosed with cancer but after talking to you and learning more about the disease I am feeling better.

CancerBro: That’s great Mr. Tiesto, can I ask you a few questions related to your disease?

Mr. Tiesto: Yeah sure CancerBro, please go ahead.

CancerBro: What were your initial complaints for which you consulted the doctor?

Mr. Tiesto: I was feeling pressure-like sensation and heaviness in my right scrotum. When I palpated it, I felt some mass in my right scrotum.

CancerBro: Did you feel any pain in the mass on applying pressure?

Mr. Tiesto: Not at all CancerBro, it is totally painless.

CancerBro: Did you have any developmental abnormalities in childhood or any sexual complaints as an adult?

Mr. Tiesto: My parents didn’t tell me regarding any developmental issues in my childhood, otherwise, I am absolutely normal as an adult with no sexual problems.

CancerBro: That’s great Mr. Tiesto, did anyone else in your family had similar complaints?

Mr. Tiesto: No CancerBro, as far as I can remember I am the first one to have any such complaint in my family.

CancerBro: Okay Mr. Tiesto, thank you very much.

What are the Risk Factors for Testicular Cancer?

The incidence of testicular cancer is highest in North-European and least in Asians and Africans.

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.

Various syndromes such as Down’s syndrome. Klinefelter’s syndrome and testicular dysgenesis syndrome may also be a risk factor for the disease.

Previous history of cancer in the opposite testis, previous testicular biopsy, testicular atrophy or impaired fertility also increase the testicular cancer risk factor.

testicular cancer risk factors

What are the Testicular Cancer Signs and Symptoms?

Most commonly, testicular cancer symptom present in the form of painless swelling, but sometimes torsion may cause severe pain.

In some cases, pressure like sensation or heaviness may be present in the testis.

Very rarely, back pain, breathlessness or a headache may be present due to the spread of cancer to bones, lungs or brain.

Testicular Cancer Symptoms and signs infographic

What are the Investigations for Diagnosis and Staging of Testicular Cancer?

 
CancerBro, if anyone comes with a testicular mass is it always testicular cancer only?
 
No, not necessarily, conditions other than testicular cancer may also be present similarly. For this, we have to further investigate the patient.
 
The next step is testicular ultrasound. 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.
 
The next step is to do blood tests, to check for tumor markers.
 
Before discussing the tumor markers in detail, we will first discuss the subtypes of testicular cancer. Testicular tumors may be broadly divided into seminomas and non-seminomas. The non-seminomatous germ cell tumors may be further divided into embryonal carcinoma, endodermal sinus or yolk sac tumor, choriocarcinoma or teratoma.
 
Now, let’s discuss the tumor markers for testicular germ cell tumors according to the subtypes.
 
First we will discus about seminoma. In seminoma, LDH is the most commonly elevated tumor marker, and beta-HCG may be elevated in some cases.
 
Next comes choriocarcinoma, in which beta HCG is significantly elevated, and LDH maybe elevated in some cases. In endodermal sinus or yolk sac tumors, AFP is significantly elevated and LDH maybe elevated in some cases. And in embryonal carcinoma all the three, that is, AFP, beta HCG and LDH maybe elevated.
 
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.
 
So after doing testicular ultrasound, tumor markers and system imaging, we are very close to diagnosis, but to be 100% sure, we require a tissue histopathology. So for that, we do high inguinal orchiectomy, in which the involved testis is removed. The procedure is both diagnostic as well as therapeutic because it provides tissue for histopathological diagnosis, as well as it removes the involved testis. 
 
The pathology report after high inguinal orchiectomy confirms the diagnosis of germ cell tumor. It also tells us whether it is a seminoma or non-seminoma or whether it is a mixed germ cell tumor, having components of both. It also tells about the sub-type of non-seminoma, that is, whether it is embryonal carcinoma, endodermal sinus or yolk sac tumor, choriocarcinoma or teratoma.
 
The tumor markers may not be elevated in all the cases, and even if they are elevated they are highly overlapping in different sub-types, so 100% diagnosis is rarely possible with just the tumor markers. Therefore, for the confirmation of the diagnosis of testicular germ cell tumor, we require both, that is histopathology and tumor markers.
 
Rarely, it is possible that histopathology shows seminoma, but AFP is elevated, such cases are related as non-seminoma. So, always remember that elevation of AFP strictly goes in the favor of non-seminoma even if the histopathological diagnosis is suggestive of a seminoma.
 
Once the diagnosis of the testicular germ cell tumor is confirmed, the next step is staging and risk stratification of the disease.
 
investigations infographic

What is the TNM Staging of Testicular Cancer?

So after discussing the normal anatomy of the testis, we now come to the T staging for testicular tumors. This figure shows the T1 stage in which the tumor is limited to the testis. It may invade the tunica albuginea but not the tunica vaginalis. There is no lymphovascular invasion by the tumor. T1 - infiltrates into the tunica albuginea Next comes the T2 disease. In this, the disease is limited to the testis or epididymis. The tumor may extend through tunica albuginea to involve tunica vaginalis, or there might be the lymphovascular invasion by the tumor. T2 - infiltrates into the tunica vaginalis This figure shows T3 disease in which the tumor infiltrates into the spermatic cord. T3 - infiltrates into the spermatic cord And here the tumor infiltrates into the scrotum, called as T4. T4 - infiltrates into scrotum
 
testicular cancer T Staging [Infographic]
 
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.
 
metastasis to retroperitoneal lymph nodes 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.
 
This figure shows M1a disease due to the involvement of lymph nodes in the mediastinum, this is non-regional lymph nodes because it is outside the retroperitoneum.
 
M1a - involvement of lymph nodes in the mediastinum Similarly, the involvement of inguinal lymph nodes is also M1a disease because it is a non-regional lymph node for testis. M1a - involvement of inguinal lymph nodes And here, the involvement of supraclavicular lymph node is non-regional.
 
M1a - involvement of supraclavicular lymph node M1a disease also includes the cases with pulmonary metastasis, that is spread of the tumor to lungs. M1a - lung metastasis Whereas, spread to the organs of the body other than lung is called as M1b. In this figure spread to liver makes it M1b.
 
M1b - liver metastasis Spread to brain or bones is also M1b.
 
testicular cancer N and M Staging [Infographic]

What are S1, S2 and S3 Tumor Markers in Testicular Cancer?

 testicular cancer tumor markers

As you can see in the above figure, the tumor markers for each subtype may be different, although there is some overlap.
 
Seminoma mostly presents with LDH and/or beta HCG elevation, choriocarcinoma with beta HCG and/or LDH elevation, endodermal sinus/yolk sac tumors with AFP and/or beta HCG elevation, and embyonal tumors may present with elevation of any one or more of three.
 
SX: Tumor marker levels are not available.
S0: Tumor marker levels are normal.
S1: At least 1 tumor marker level is above normal.
  • 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.
S2: At least 1 tumor marker level is substantially above normal.
  • 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.
S3: At least 1 or more tumor marker level is very highly elevated.
  • LDH > 10 times the ULN
  • beta-hCG > 50,000 mIu/mL, and/or
  • AFP > 10,000 ng/mL.

What is Testicular Cancer Stage Grouping?

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.
 
testicular cancer Staging Summary
STAGE TNM  
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 the Treatment of Testicular Cancer?

Treatment for Seminoma Germ Cell Tumor

The seminoma testicular cancer treatment depends on whether it is seminoma or non-seminoma. First, we will discuss the treatment for seminoma.

The treatment options for stage 1 seminoma are surveillance, radiation therapy or chemotherapy. Surveillance is usually preferred from T1 to T3 disease. The final decision is taken by the oncologist after assessing the patient’s condition and discussing all the treatment options with the patient.

For stage 2 seminoma, the treatment depends on whether it is stage 2A, 2B or 2C. For stage 2A, the treatment options are radiotherapy and chemotherapy. For stage 2B also, chemotherapy and radiotherapy are the treatment options but chemotherapy is preferred over radiotherapy in most of the cases. And for stage 2C, chemotherapy is the treatment of choice.

For stage 3 disease also, chemotherapy is the treatment of choice.

Seminoma testicular cancer treatment So these were the treatment options for seminomatous germ cell tumor, but the final decision is taken by the oncologist after assessing the condition of the patient and discussing with the patient the toxicities with various treatments.

In some cases of seminoma, the residual disease may be present even after chemotherapy. In such cases, surgery may be required depending upon the scan findings and if a viable tissue is found after surgery further chemotherapy is given.

Treatment of Non Seminoma Germ Cell Tumor

Now we come to the Non-seminoma testicular cancer treatment.

The treatment options for stage 1 non-seminoma are surveillance, surgery or chemotherapy. Surveillance is usually preferred in T1 disease. The surgery that is done for non-seminomatous germ cell tumors is called as retroperitoneal lymph node dissection or RPLND.

Treatment for stage 2 non-seminoma depends on whether the markers are S0 or S1, that is whether they are normal or elevated. If the markers are elevated, then chemotherapy is the treatment of choice. For stage 2 disease with normal markers, the treatment depends on whether it is stage 2A, 2B or 2C. For stage 2A disease, the treatment options are surgery or chemotherapy. For stage 2B disease also, the treatment options are the same, but chemotherapy is preferred over surgery. And for stage 2C disease, chemotherapy is the treatment of choice.

For stage 3 disease also, chemotherapy is the treatment of choice. So, these were the treatment options for non-seminomatous germ cell tumors.

non seminoma testicular cancer treatment Again, always remember that of all the treatment options the final decision is taken by the oncologist, after assessing the condition of the patient and discussing the various treatment option with the patient.

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