Download Testicular Cancer

An essay by Peter Perskull
AMS 2000
Testicular Cancer
Introduction:
Testicular cancer is an unusual form of cancer that accounts for about 1% of all cancer in men.
It is the most common form of cancer in the age group 15 - 35 and it is more common in Caucasian
men then in men of any other ethnic group. The tumour is usually confined to one testicle.
In most cases testicular cancer, there is a germ cell tumour; only about 5% are of a somatic origin.
Thirty years ago, testicular cancer accounted for 11.4% of all cancer deaths in the 25- to 34-year-old
age group, with an overall 5-year survival rate of 64%. Now it is highly treatable and has a cure rate
closing on 100%.
The biggest concerns usually evolve continued fertility after the treatment of the tumour and enhanced
risk for a second tumour. The earliest symptom of testicular cancer is, most often, pain, swelling, or
hardness in the testis, or some combination of these symptoms.
Testicular cancer:
Epidemiology and Aetiology:
Testicular cancer can occur at any age but is most common between the ages of 15 and 35 years. There
is a secondary peak in incidence after age 60. Seminoma (se below) is the most common tumour type
in the older population but is rare in those under age 10. (Patrick J et al)
The incidence of testicular tumours is approximately 3-4 cases per 1,00,000 males each year. The
incidence is believed to be doubling every 30 years for the white males. It is lowest in AfricanAmericans. Geographically the incidences are highest in Scandinavia, Switzerland and Germany (5-6
cases per 1,00,000 males annually), intermediate in USA and UK while it is lowest in Asia and Africa
(0.8 per 1,00,000 males in Japan annually). A demographic chart is presented below in figure1.1.
Figure 1:Demographic chart over the cases of testicular cancer
Risk factors:
What causes testicular cancer?
The most common risk factor is to have an undescended testicle or cryptorchidism. One of the testicles
has not descended into the scrotum and remains in the lower abdomen. The level of decent of the
testicle appears to have a correlation with the risk of tumour development. The risk remains even if
surgery is preformed to move down the testicle into the scroutum. There is also a connection with the
sex chromosome disorder Kleinfelter’s syndrome, which is characterised by smallness of the testicle.
Also thought to be at greater risk are patients with testicular feminization, true hermaphrodites and
individuals with persistent müllerian syndrome. A history of previous testicular cancer also increases
the risk of getting cancer in the second testicle. In comparison to monozygotic twins there may also be
an increased risk for testicular cancer in dizygotic twins, which is believed to have a connection to
increased oestrogen exposure.
Recent studies in Norway and Sweden suggest there is a high-frequency recessive gene in familial
testis cancer, as the frequency of relatives with testis cancer was higher than otherwise expected.
There are signs that being HIV-positive may increase the risk, but there has been little hard data. So far,
research has not yet shown a connection between testicular cancer and any particular habits, activities,
or lifestyles. It has been speculated that physical injury to the testis increase the risk of testicular
cancer, but that is most likely just a result of the detection of the tumour during a medical examination
of the injured area.
Physiology:
The physiology of testicular tumours is quite complex with various types of cancer cells.
About 95% of testicular tumours are of germ cell origin (GCT) and the rest of the 5% are of other
histological types. It is often malignant, but if detected early it has a good cure rate. Even in late stages
of the cancer the cure rate is relatively high.
Germ cell tumours are broadly divided into two groups, seminoma and nonseminoma, where seminoma
is the less aggressive and more sensitive to treatment, especially radiation therapy. Seminoma is most
common type and it makes up about 30-50% of the testicular cancers. It occurs when germ cells
become cancerous in a very early stage of development.
Nonseminoma is divided into for groups, embryonal cell carcinomas; teratomas; teratocarcinomas; and
choriocarcinomas. Most tumours are mixed tumours with two or several kinds of different
nonseminoma cells and / or seminoma cells. Only about 40% of all GCT are of a single type (se table
1) while the rest diplay a mixed histology. Those tumours is called mixed tumours and are medically
treated ha nonseminomas.
Table 1 Frequencies of single cell type GCT
Percent
Tumour showing single cell type
Seminoma
26.9%
Embryonal carcinoma
3.1%
Teratoma
2.7%
Choriocarcinoma
0.03%
Yolk sac tumor
2.4%
The progress of the cancer is divided into three different stages, based on how much it has spread
throughout the body. In stage one the tumour is only found in the testicle. In stage two it has spread to
the para-aortic lymph nodes, usually in the kidney region. Stage three means it has spread beyond the
para-aortic lymph nodes to organs in the abdominal cavity above the diaphragm. Depended on if the
cancer is bulky or non-bulky (se below), it may shave spread differently. Non-bulky is usually confined
to lymph nodes and the lung, whereas the bulky subtype may have spread to other organs such as liver
and brain.
Stage two and three cancer may also be divided into bulky and non-bulky. The division between bulky
and non-bulky depends on whether the lymph nodes in the abdomen can be felt or not and the size of
the tumours.
Genetics:
The genetic background to testicular cancer is complex. It is connected to a problem on chromosome
12. There seems to be a tandem multiplication of the short arm of chromosome 12, in germ cell
tumours, an i(12p). As it is a unique change, it has been used as a genetic marker. (National Center of
Biotechnology Information)
This results in overproduction of different factors, especially cyclin D2, which may have a role in the
development of testicular germ cell cancer. Testis cancer is a tumour suppressor based cancer, so the
duplication of 12p isn’t the whole picture. Deletions in 12q13, 12q24 and 5p15 have also been
detected. Some of these deletions are known to play a role as tumour suppressors in other forms of and
the other deletions are thought to have that function as well.
Treatment:
(Source: CancerNet )
Treatment of the cancer depends on which stage it is in and on which type of testicular cancer it is.
As there is a big variety in the types of testicular cancer the form of treatment is diverse. In most cases
it involve surgical removement of the testicle, or radical inguinal orchiectomy, and in most cases this is
combined with radiation and / or chemotherapy.
Broadly the type of therapy is divided on the bases if the tumour is of seminoma or nonseminoma type.
This is done since seminoma tumours are more sensitive to radiation therapy.
In general a vascular invasion by the tumour results in a higher recurrence rates, and therefore
treatment usually withhold until signs of recurrence are noticed, may be aplyed.
Stage 1
Seminoma
The cure rate of a seminoma in stage 1 is greater then 95 %,
If a seminoma tumour is found, treatment will probably be surgery to remove the testis
(radical inguinal orchiectomy), followed by external-beam radiation to the para-aortic lymph
nodes in the abdomen.
Treatment can also include radical inguinal orchiectomy alone followed by careful testing to
see if the cancer comes back. The overall reoccurrence rate is usually about 15%, which is
then treated by radiation treatment. The cure rate is almost identical whatever method used.
Nonseminoma
The Nonseminoma cure rate is also above 95%.
There are generally two ways of treatment.
1. Removal of the testicle followed by retroperitoneal lymph node dissection, removal of
some of the lymph nodes (in adults). If preservation of fertility is of importance a nerve
sparing technique can be used that preserves the ejaculation ability (RPL= retroperitoneal
lymphadenectomy). It seems to be as effective as the regular method. This is followed by
monthly examinations for relapseation. If the cancer returns chemotherapy is employed.
2. Radical inguinal orchiectomy alone followed up with regular controls. If relapsed
chemotherapy is used.
Stage 2
Seminoma
The treatment is divided into to categories depending if the tumour is considered bulky or nonbulky (se above for definition of bulky and non bulky). They have a cure rate higher then
90%.
 Nonbulky
Radical inguinal orchiectomy followed by radiation to the retroperitoneal and ipsilateral
pelvic lymph nodes.
 Bulky
Radical inguinal orchiectomy followed by combination chemotherapy (with a cisplatin-based
regimen), or by radiation to the abdominal and pelvic lymph nodes. Recurrence rate is higher
after radiation for bulky stage II tumors than radiation for non-bulky tumours.
Nonseminoma
The stage two nonseminoma are highly curable and has cure rates above 95%
The method of treatment varies from case to case.
1. Radical inguinal orchiectomy, removal of retroperitoneal lymph nodes followed by
monthly check ups. If there is a relapse complete the treatment with chemotherapy.
2. Radical inguinal orchiectomy followed by removal of retroperitoneal lymph nodes
followed by chemotherapy and then monthly checkups.
3. Radical inguinal orchiectomy followed by chemotherapy with delayed surgery for
removal of residual masses in lymph nodes (if present) followed by monthly checkups.
Stage 3
Stage three tumours are usually curable (70%). They are generally treated with radical
inguinal orchiectomy, combined with chemotherapy, and surgery to remove residual masses.
Clinical trials with high-dose chemotherapy combined with bone marrow transplantations are
being conducted as well.
In those who aren’t cured with standard chemotherapy usually have widespread visceral
metastases, high tumour markers, or mediastinal primary tumours at presentation.
Fertility and other consequences of treatment:
Because testicular cancer rarely occurs in both testes, a patient's remaining testicle can maintain
hormone levels and fertility. Even with the remaining testicle 40% to 70% of patients that has suffered
from testicular cancer are hypofertile, at least temporarily. Radiation therapy also has a depressive
effect on spermatogenesis as has chemotherapy. Sperm cells are fast dividing cells and therefore they
will be targeted by therapeutic methods. If care to preserve fertility isn’t taken ejaculation problems
will be a result of surgery of the lymph nodes (retroperitoneal lymph node dissection).
As with all cancer treatment chemotherapy will result in hair loss and other more classic side effects.
Discussion:
Testicular cancer is a cancer that affect relatively young people. It usually have big psychological
impact on the persons with the disease, and there are many forums giving support for people that feel
that there manhood has been crippled. Information of the cancer is necessary to increase the chances to
find the tumour early . Many physicians suggest that a monthly self-health exam is made to check for
any irregularities in the testis.
The prognosis of testicular cancer is good, and it is a form of cancer that has been successfully treated
during the last 20 years. It has less effect on fertility now days and alternative methods of surgery may
preserve even more of the reproductive function of the diseased.
The causes of the disease are not clear and since there has been an increase in the number of cases the
last years it may be important to understand why. Environmental factors has been suggested, but as
always this is hard to prove.
Overall the treatment and prognosis of testicular cancer has improved and are still improving.
References:
Murty, V. V. V. S.; Chaganti, R. S. K.
A genetic perspective of male germ cell tumors. . Semin. Oncol. 25: 133-144, 1998.
(From their abstract)
Tomatis. L, (WHO). Cancer: Causes, Occurrence and Control. 1990
Jacobsen R, Bostofte E, Engholm G, Hansen J, Olsen JH, Skakkebaek NE, Moller H.
Risk of testicular cancer in men with abnormal semen characteristics: cohort study.
BMJ. 2000 Sep 30; 321(7264): 789-792.
Lancet 1997; 350: 1723-28.
CancerNet – a service from the national cancer institute
http://cancernet.nci.nih.gov/cancer_Types/Testicular_cancer.shtml#toc2
Graeme S. Steele, MBBCh, FCS, and Jerome P. Richie, MD.
Oncology Vol 11, No 5 (May 1997)
http://www.cancernetwork.com/journals/oncology/o9705e.htm
Patrick J. Loehrer, MD, Thomas E. Ahlering, MD, and Alan Pollack, MD, PhD
Testicular Cancer, Cancer Management: A Multidisciplinary Approach Fourth Edition (2000)
http://www.cancernetwork.com/handbook/Testicular.htm
Laurence H. Klotz, MD. Canadian Medical Association Journal 1999; 160:213-4
http://www.cma.ca/cmaj/vol-160/issue-2/0213.htm
Health Oasis - MayoClinic
http://www.mayohealth.org/mayo/9511/htm/testica.htm
Memorial Sloan-Kettering Cancer Center
http://www.mskcc.org/patients_n_public/about_cancer_and_treatment/cancer_information_by_type/tes
ticular_cancer/index_body.cfm?#CGI.PATH_INFO#
National Center of Biotechnology Information
http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?273300
OncologyChannel
http://www.oncologychannel.com/testicularcancer/
National Cancer Data Base (NCDB)
http://www.facs.org/about_college/acsdept/cancer_dept/programs/ncdb/testis1.html
The Cancer Journal - Volume 11, Number 5 (September-October 1998)
http://www.infobiogen.fr/agora/journals/cancer/articles/11-5/vane.htm#4