Description of the Normal Penis:
The penis is the flexible, expandable male organ; its foreskin is sometimes removed ("circumcision") for religious or perceived hygienic reasons. This penis is comprised of a "shaft" of variable length (average of 5 inches) which arises from the "pubis"
-- the area where the pubic bones join in front. The penis has a "head" atop of the shaft, the largest diameter of the penis is where the head starts and
is called the "corona" (meaning crown). The "urethra" is the hollow tube at the center of the penis, it extends from the neck of the bladder
to the opening at the tip of the penis ("urethral meatus"). The urethra is divided into 3 portions, the "prostatic"
, "membranous"
and "spongy" urethra. Only the spongy urethra, which is the part within the penis, is considered
part of that organ. The urethra carries urine from the bladder and sperm from the
testicles to exit the "urethral meatus" opening at the penile tip. Neither the "testicles" within the "scrotal sac"
, nor the "prostate gland" which enlivens sperm, is considered part of the penis proper-- although the both
feed into it to discharge their fluids through it.
If one slices the penis like a sausage, the urethra is the small central tube within
the organ. The urethra opens up near the tip of the penis, inside the head, into
an area called the "fossa navicularis" (meaning "boat-like" opening). Since the urethra is normally so narrow (only about
4 millimeters in diameter) it is subject to "stricture" from infection, inflammation, injury, scarring, cancer or its treatments-- which
will interfere with the egress of urine and sperm if unrelieved. The spongy urethra
within the penis proper is surrounded by a "loose connective tissue" called the "corpus spongiosum" (meaning "spongy body"). This tissue becomes more prominent at the head of the penis,
in fact lying directly below the skin there. The corpus spongiosum is flexible and
helps protect the delicate urethra. The shaft of the penis is home to a set of paired, expandable tubes, called the "corpus cavernosum" (meaning cave-like body). These are the tubes which fill with blood to expand the
penis during erection. They lie along the shaft of the penis, from where it orginates
(the "crus"
of the penis) at the point where the pubic bones join ("symphysis pubis") and extend to the head of the penis. Both the length of the penis and the shaft diameter
increase during erection. The penis is connected to the pubic bones by the "suspensory ligament of the penis" which allows it to dangle. It blends into a fibrous coating, called "fascia"
, which surrounds the shaft of the penis under the skin and thereby encloses urether,
corpus spongiosum, and 2 corpus cavernosum. The top surface of the penis, as viewed
when erect, is called the "dorsum". The loose tissue on the underside of the head is the "prepuce"
, from which the foreskin may be removed by circumcision.
The corpus cavernosum and corpus spongiosum fill with blood during erection, the
source of that blood are branches from the "dorsal artery of the penis" which arises from the "internal pudic" artery, which itself is a brach of the "anterior
iliac" artery, which branches off of the large "desceding aorta". There are also
smaller arteries from the internal pudic carrying blood to the "bulb" of the penis (which is the very first portion in front of the pubic bones), and an
artery to the "corpus cavernosum". The blood drains from the penis primarily by the "dorsal vein of the penis" and into similarly named venous branches as above, and is ultimately returned to
heart by the large "inferior vena cava". The main blood vessels of the penis lie
directly beneath the skin and fascia membrane coating, together called "integument". The draining veins of the penis can act as conduits for spread of "local" infections or cancer, and carry local diseases to anywhere in the body to become "systemic".
The signal to fill with blood for an erection, or conversely to drain blood and become
flaccid, are controlled by nerves to the penis. The "parsympathetic" nerves from the "nerves erigentes" in the pelvis cause blood to flow into the corpus
cavernosum, engorging and enlarging the penis. The "sympathic" nerves from the "sympathetic chain" along the spinal cord allow the draining veins
to dilate and the penis to shrink to flaccidity. The parasympathetic system is more
active at night, explaining why men have erections while sleeping ("nocturnal erections"). Monitoring for the presence of these with a pressure gauge ("plethysmography") can distingish physical inability to achieve erection ("impotency") from psychological inability to do so. Over 70% of the time the failure to achieve
erection is for psychological reasons, but even so many of these men can get an erection
with new drugs like "Viagra" (Pheizer Pharmaceuticals) which stimulate blood flow to the penis.
The penis also has a system of "lymph channels"
which collect the tissue fluid that seeps out of the smallest blood vessels ("capillaries")
to nourish individual "cells"
(the smallest unit of life). There are two sets of lymphatics to the penis, the "superficial"
and "deep" lymphatics. The former collect "lymph fluid" from the skin, prepuce and inner lining ("mucosa") of the urethera, while the latter emerge from the corpus spongiosum and corpus cavernosum.
The lymph channels carry the lymph fluid to regional "lymph nodes"
, which are normally pea-sized glands that are filled with White Blood Cells. These
"nodes" filter and purify the lymph fluid, which is acually the fluid ("serum") portion of the blood. When germs or cancer cells are trapped by lymph nodes, they
swell ("lymphadenopathy"). By definition, swelling means the lymph nodes are larger than 1 cm. (~1/2 inch)
apiece. The lymph nodes "chains" tend to interconnect, but generally follow established
pathways. The "superficial" lymph nodes of the penis drain to the "external inguinal" nodes, they are located on both inner upper thighs. The "deep" lymph nodes of the
penis drain into the deep "pelvic" lymph nodes, and eventually these a continuous with "para-aortic" lymph nodes which run back up toward the heart. Ultimately, all the lymph fluid from
whatever location converges to rejoin the bloodstream, at the "left thoracic duct" region near the heart. The lymph system can act as a conduit for the spread of infections
or cancer, but may also help trap these diseases to keep them localized.
What is Penile Cancer?
The penis is composed of various "cells"
, which are intricately combined together into "tissues" which form the "organ". The penis contains fat, muscle and skin cells. These cells divide to produce new
ones, and grow very rapidly during womb life, early childhood and puberty. In adulthood,
new cells are produced only to replace those that die of old age, injury or disease.
Normally, division of cells is under very tight control. This control is exerted by
the "genes" inside each cell, which are housed in long clumps forming "chromosomes"
, which are visible under a light microscope. The genes themselves are made up of
DNA
, the master genetic code material. If the genes are damaged, say by chemicals or
radiation, the control over cell division may be lost in one particular cell. Ultimately,
cancer is considered a disease of the DNA. Penile cancer starts in a single cell. That cell starts dividing haphazardly, making millions and billions of copies of
itself. It takes up the nourishment needed by other cells, depriving them so the
cancer can continue to grow. Quickly growing cells can clump up to form a "tumor". A tumor simply means a swelling, it can be caused by inflammation or infection.
A "benign" tumor only grows in it's local area (although it may get quite large)-- it cannot
spread and is not
cancer. By contrast, a tumor which can spread to other body areas is called "malignant" and this is cancer. The process of cancer spread to other areas is called "metastasis"
, so only malignant tumors (i.e. cancer) can metastasize. Theoretically, cancer can
spread to any area of the body, and it often grows better in it's area of spread than in it's area
of origin ("primary site"). It is this capacity for spread that makes cancer so dangerous. If not treated successfully,
penile cancer ultimately kills by urinary blockage, debility, anemia, infection,
and damage to distant organs like the liver and brain.
How Common is Penile Cancer?
Penile cancer is relatively rare; each year there are 1500 new cases in the USA. It causes 400 deaths annually. It represents 4% of all "urogenital"
cancers; urogenital means those of the kidneys, bladder, prostate, testicles and
penis. Obviously, all cases are in males, and the average age is 60 years old. In
America, an average of 1 out of 100,000 men per year develop penile cancer. In other
areas of the world (i.e. Africa, Asia) where fewer men are circumsized, penile cancer is
more common. In Paraguay, for instance, it is the most common urogenital malignancy,
accounting for over 50% of male cancers! Also in Uganda, where men are not circumsized, penile cancer is the most common type of cancer found in males. In general, the incidence
(meaning number of new cases per year) of penile cancer in the United States has
been increasing, owing to sexually transmitted diseases that predispose to cancer--
especially in homosexual men.
What Causes, or Increases the Risk, for Penile Cancer?
As for any cancer, the exact reason why one man developes penile cancer and another
does not remains unknown. However, these "risk factors" increase the risk:
1) Being Uncircumsized
is a definite risk factor for getting penile cancer, due to the difficulty in keeping
the area under the foreskin clean. Poor penile hygiene in uncircumsized men raises
the risk of cancer to as high as 1 in 600. Glands near the head of the penis secrete
"smegma"
, which also contains shed skin cells and bacteria. Smegma has been shown to be "carcinogenic"
(meaning
causitive of cancer) in animals. Even if a man keeps the foreskin area clean, it is
impossible to totally prevent some buildup of smegma. Cancer of the penis remains
exceedingly rare in circumsized men.
2) Sexually Transmitted Diseases are less proven to cause cancer than poor penile hygiene, but some association ("correlation")
exists. This is also found for vulvar cancer in women, since the vulva and clitoris
in the female are the counterparts of the scrotum and penis in the male. Specifically, viruses like Human Papilloma Virus ("HPV")
, especially subtypes 16 and 18, are shown to increase the rate of skin cell ("epithelial
cell") division in the penis. Other diseases which may increase the risk for penile
cancer include syphillis, chancroid, and granuloma inguinale.
3) Lowered Immunity from immune system destroying viruses (i.e. HIV) or from immune suppressing medications
(such as those taken after transplanting an organ to avoid rejection) are correlated
with a wide range of cancers, with penis cancer also increased. Particularly the
risk for "Kaposis Sarcoma"
, a local form of cancer which can occur anywhere on the body, is higher for men with
the "AIDS" syndrome from the HIV virus. Normally the immune system has a "surveillance" for
early cancers and destroys them before they get out of control. However, with lowered
immunity this "immunosurveillance" is then compromised, so early cancer cells escape detection, and can grow into large
tumors. The rate of spread of cancer is faster in people with low immunity.
4) Persistant Irritation of any sort, whether from a catheter tip, tight fitting under- garments, applied
chemicals, poor hygiene or chronic viruses is a common link to getting urogenital
cancers. Irritated cells divide more frequently in an attempt to repair perceived
injury. The more commonly cells divide, the higher the chance for a genetically unstable one
to arise, and start dividing without regard for the normal gene control mechanisms.
Again, cancer is caused by genetic damage, when the control of a cell's division
goes awry.
5) Precancerous Lesions of the penis means those that are not yet frankly a cancer, but have a high chance
to become one. These include "leukoplakia"
, a white skin plaque on the penis, "Erythoplasia of Queyrat" which is a raised, velvety sore, "Bowen's disease"
, that is a red plaque, "Balanitis Xerotica Ob- literans",
which is scaly withering, and "Busche-Lowenstein"
that is wart-like.
***Tobacco and Alcohol have NOT been linked to penile cancer, but a recent study
has found tobacco related to a higher risk for vulvar cancer, so it is possible
that future study will link it to penile cancer also.
What are the Signs and Symptoms of Penile Cancer?
A "sign" is something that can be measured, like the diameter of a sore or a fever, while
a "symptom" is something the patient feels, such as pain or fatigue. The way a patient with a
disease looks when they first come to the doctor with it is called their "presentation"
, and physicians are trained to take careful note of the initial presentation when
diagnosing a specific disease. By far, the most common diseases of the penis ARE
NOT cancer, so the doctor has to have a "high index of suspicion"
to even consider cancer as a possibility. Patients often delay coming to a physician
for problems with their "private areas", from a sense of embarrasment and just hoping
the problem will go away on its own. While many non-cancerous problems of the penis
will go away without specific treatment, a cancer problem comes and stays without proper
treatment. The average delay is one year before a patient seeks tratment. When a
patient first "presents"
to their doctor with an abnormality ("lesion")
suspicious for penis cancer, the most common initial "findings" are:
1) A Skin Sore that doesn't heal but instead slowly growths (over months). The most common location
for this is on the underside of the head, at the "glans" area (covered by the foreskin in uncircumsized men). The sore may be in the form
of an "ulcer"
, that is an indentation from the normal area, as a "plaque"
that is slightly raised from the surrounding normal area, or as an "exophytic" (wart-like) lesion. The cancer may grow into an actual "mass"
, which means a firm growth, and may bleed, flake, or become infected. It is usually
painless unless it becomes inflammed or infected. Kaposi's Sarcoma appears as a puplish and slightly raised area on the head or the shaft of the penis;
these areas are often tender to touch.
2) Discharge from the penis, showing the organ has become infected owing to an invading cancer.
Since poor hygiene of the genital area, and foul smegma, are predisposing factors
to penile cancer, it is not surprising that the area will easily become infected.
The cancer can eat down deeply into penis and invade the delicate ureter, which is a
set up for infection. Discharges due to infection often contain pus, blood, and
smell putrid. They will commonly respond to an antibiotic, and while such medication
will improve symptoms it does nothing to treat underlying cacer.
3) Difficulty Urinating is common as the cancer advances and spreads to the urethral meatus (opening) or
the urethra proper. The ureter may either be com- pressed due to tumor pressure
from outside of it ("extrinsic compression") or may be blocked ("obstructed")
from tumor or scarring (due to infection) inside of it. When the ureter crimps down
upon itself owing to scarring this is called "urethral stricture". Normally, dribbling of urine still occurs to drain the bladder but if the obstruction
becomes complete, this is obviously a surgical emergency.
After the bladder fills, if it cannot empty then it exert urine back-pressure up to
the kidneys, which are connected to the bladder via the paired "ureters". Pressure upon the kidneys damages their delicate structures ("renal papilla) which spray newly formed urine into the hollow part ("pelvis") of the kidney; the pelvis then drains the urine into the bladder via the urethra
tubes. If the kidneys become damaged from excessive urine back pressure, they swell ("hydronephrosis")
and begin to fail. When the kidneys fail, they fail to clear ammonia from blood,
and this builds up ("azotemia") leading to mental dullness, fatigue, and eventual coma and death. A patient with
total kidney failure can only be rescued by doing a "dialysis"
filtration of the blood to purify it. in fact, azotemia is a common cause of death
from advanced penile cancer.
4) Lymph Node Enlargment-
- "lympadenopathy"
is occasionally the first sign, but
usually means "locally advanced" disease. The most likely lymph nodes to be swollen are the "superficial inguinal"
nodes at each inner upper thigh; this is where the superficial lymph node channels
of the penis drain to. Recall that the deep lymph channels of the penis drain to
the deep pelvic lymph nodes, which will usually not cause any symptoms until they
are very large. When they become very large, they can cause pain, and problems with urine voiding
and moving the bowels. It is important to note that infection may be the only cause for the lymph node swelling, but it is also possible to have
lymphadenopathy due to infection and cancer spread at the same time. However, infection
usually stays within the lymph node, but cancer may eventually cause the capsule
of the node to rupture as it enlarges. If the deep lymph nodes of the pelvis are involved,
they drain up into the "para-aortic" nodes along the spine, and so may cause backaches.
5) Signs of Distant Spread
are usually only seen with very advanced disease, even though a cancer can theoretically
spread anywhere at anytime. The most common areas of distant spread are bone, liver,
lung, and brain. Developing new problems in these areas in a patient with penis cancer is suspicious, but not proof, of cancer spread there. Only by taking an actual
piece of the area of [possible] spread for microscopic examination, or occasionally
a sophisticated radiological imaging study (e.g. CT scan or MRI) can the spread be
confirmed.
Can Penile Cancer Be Prevented?
Being circumsized as a child is the main decreasor of risk for penile cancer, getting
this operation later in life is not as preventative but may reduce risk. Especially,
patients with recurrent infections under the foreskin area ("ballanitis") are usually offered circumcision. For uncircumsized men, keeping the prepuce area
clean of smegma is important. Also, staying with a single sexual partner ("monogamy") reduces the risk of sexual transmitted viruses that can predispose to cancer. Any
new abnormal area ("lesion") on the penis that doesn't quickly heal should be shown to a competent physician,
as should swollen lymph nodes in the groin which don't quickly resolve on their own.
Any signs of venereal disease (e.g. syphillis, gonorrhea, chancroid) should be prompty
diagnosed and treated.
What are the Types of Penile Cancer?
Over 90% are "squamous cell carcinoma", this means a cancer that arises from the lining "epithelial" cells of the body (e.g. skin, mucous membranes). About 5% are "sarcomas"
, particularly "Kaposi's Sarcoma"
, which arises from the "mesenchymal" cells of the penis (i.e. fat, muscle, cartilage). Another 3% of cases are "basal cell carcinoma" which is also a form of skin cancer, arising from epithelial cells. Melanoma accounts for about 1% of cancers of the penis, it arises from the "melanocyte"
cells which produce "melanin" pigment to darken and protect the skin.
Rarely (less than 1%) we see lymphoma from immune cells or spread ("metastasis"
) from other "primary cancers" (i.e. lung, prostate, pancreas) to the penis. The treatment for these rare types
is discussed where they are more common.
How is Penile Cancer Detected and Evaluated?
When a first patient "presents" to their physician with signs and/or symptoms suspicious for penile cancer, the
following "evaluation" is standardly done:
1) Complete History and Physical examination, the doctor notes "symptoms"
(that which the patient feels, e.g. pain) and "signs" (that which can be measured e.g. tumor size or fever). Any abnormalities of the penis
are carefully noted and obvious cancer is measured. The area is felt ("palpated")
for tenderness. The groin is examined for enlarged glands ("inguinal nodes") and the size is noted if present. A rectal exam is done to see if the anus or lower
bowel seems involved. A full physical exam is proper to detect signs of distant spread
or other illness.
2) Blood and Urine Tests
are to assess general health; there are no special blood tests ("tumor markers") yet to detect spread of squamous cell cancer as for some other cancers. Routine
tests will include Complete Blood Count ("CBC") to look for anemia and infection. A Blood Chemistry Panel ("SMA") measures sodium, potassium, blood sugar, cholesterol and liver and kidney function.
If a major surgery is contemplated, blood tests for clotting ability (PT, PTT and bleeding time
) are standard. A Urinalysis (UA) to check for protein, blood or infection completes the lab tests. A carefully collected ("clean catch")
urine is sent for "culture and sensitivity" to identify the bacteria in it and the antibiotics that bacteria is susceptible
to. This is especially important if there are complaints of burning or itching ("dysuria")
during urination or a discharge.
3) Imaging Tests
are done in the radiology department and standardly include a Chest X-ray to look for signs of infection or lung tumors. An Intra-Venous Pyelogram ("IVP") if often used to see if there is any obstruction blocking the kidneys, ureters,
or bladder. Recall that advancing penile cancer often will obstruct these areas.
IVP is also good for identifying radio-opaque kidney stones, a common cause of
blood in the urine and pelvic pain. IVP is generally a safe test; the main danger is an allergic reaction to the injected
dye, or the kidneys shutting down from this dye
.
When cancer invades
the ureter, anus, rectum or bladder wall, tests are done for local spread. CT scan
in "thin slices" of the tumor area helps define the extent of the tumor, and is excellent
for looking for spread to lymph nodes in the pelvis which can not be detected on standard physical exam. This will also
show swollen lymph nodes in the inguinal area. Another valuable test to study
soft tissues and lymph nodes in the pelvis is the expensive magnetic Resonance Imaging (MRI) scan.
MRI uses magnetism instead of radiation, allows the area to be viewed in three dimensions.
It is great for looking at the tumor as well as checking local muscle, fat and
nerves
for signs of invasion by cancer. Contrast material
can be injected into the blood- stream prior to either CT scan or MRI, the contrast
runs through and highlights blood vessels. If getting a CT with contrast
, ask for "omnipaque" contrast; other types are less expensive but more likely to cause an allergic reaction.
For MRI scans, a different type of contrast, called "gadolinium" is used. If bowel invasion is suspected, a Barium Enema may be ordered, where some
contrast is put through the anus and X-rays taken. Other more exotic tests are only
obtained in the presence of suspicious symptoms. For instance, a bone scan is gotten if there is new bone pain, a CT of the chest is ordered when
the plain Chest X-ray appears to show tumor in the lung, and a CT of the Brain is
gotten if new neurological symptoms occur. If major surgery
is contemplated, Lung Function Tests ("FEV")
may be done in the pulmonology department to assess lung capacity. An EKG is gotten to rule-out recent heart attack, and if heart abnormalities are suspected
a stress-thallium and/or echocardiogram
look at the heart. Tests can be ordered to look at any area of the body-- but only
if necessary. There is no point in ordering a possibly painful and expensive test
if it's results cannot change the planned therapy for the patient.
4) Cystoscopy and Proctoscopy means putting a visualization tube up the urethra and into the bladder
, and up through the anus and into the rectum
, respectively. These tests are done by a " "urologist"
, a surgeon who specializes in general urinary tract cancers. We need to see if the
inner lining ("mucosa") of the bowel and/or bladder is invaded, as this will have
treatment consequences. These tests may be done during a deep pelvic "Exam Under Anesthesia" (EUA).
5) Biopsy
(sampling) of the tumor
makes the ultimate diagnosis of whether cancer is present or not, and specifies the
particular type. A biopsy may be "excisional"
for a small tumor, meaning the whole thing is removed with a surrounding safety margin,
or "incisional"
for a large tumor, taking a small piece to confirm or deny cancer. Normally a "wedge biopsy" is taken of penile sores ("lesions") which will not remove the whole suspicious
area unless it is very small (less than 2 cm~ about 1 inch). This biopsy is taken
under local anesthesia with numbing lidocaine. The biopsy material will be sent
to the pathologist who examines it with special stains, looking for the frequent cell divisions
and abnormal nuclei (center of the cells) that signifies cancer. The pathologist
will often "grade" the cancer by how aggressive it looks.
"Grade I" looks a lot like the normal tissue or origin and doesn't have very many cell divisions,
it tends to be non-aggressive ("indolent"). "Grade III"
has very many cell divisions, scarcely resembles the tissue of origin, and tends
to be very aggressive. "Grade II"
is intermediate in behavior. If melanoma
is seen, the pathologist specifies the "depth of invasion" into the skin ("Clark's
or Breslow"), which is important for determining whether melanoma has spread distantly.
A pathologist's report often takes several days (of anxious waiting) to complete.
For sarcoma of the penis, an evaluation for Immune Deficiency will be done if HIV
is known or AIDS is suspected. Sarcoma is not graded the same way as Epithelial
Cancers (i.e. squamous cell, basal cell, melanoma) and neither are the rare lymphomas
of the penis. Any cancer which has spread (metasta- sized) to the from another body area
is NOT considered penile cancer, instead it is named after it's location or tissue
of origin.
How is the Extent of Penile Cancer Gauged?
Like all cancers, the extent of penile cancer is described by the "stage". The staging system in widespread use is from the American Joint Committee on Cancer
("AJCC"). It is for the common epithelial cancers, but not for sarcoma or melanoma:
"Stage I"
means the cancer is limited to the connective tissue just under the skin.
"Stage II" means the cancer has invaded the corpus spongiosum, the corpus cavenosum, or both--
and/or has gone to a superficial groin lymph node.
"Stage III" means the cancer has invaded the urethra or prostate, and/or has gone to multiple
superficial groin lymph nodes (on one or both upper thighs).
"Stage IV" means the cancer has spread to adjacent structures (e.g. scrotal sac, rectum,
or pelvic bones), has spread to deep inguinal or deep pelvic lymph nodes, or has
spread distantly to any other organ (e.g. lung, liver).
What is the Survival with Penile Cancer?
This depends upon the subtype of cancer, stage, therapy selected and other medical
conditions the patient suffers from ("comorbid conditions"). In general:
Stage I 95% (survival at 5 years)
Stage II 80% "" " ""
Stage III 60% "" " ""
Stage IV 30% "" " ""
For stage IV
, with pelvic node involvement, survival drops to about 20%, and with more distant
spread including para-aortic lymph node involvement, to about 10%. However, note
that some patients with para-aortic lymph node involvement are still curable. Often
even patients with extensive local disease do better than the above numbers suggest. With
distant spread to lung, liver, bone or brain survival falls to less than 5% at 5
years.
***The above textbook numbers are AVERAGES, they do not tell how well any given patient
will do. The numbers include death from all causes, including heart attack, accident,
or some other cancer. Remember that many patients with penile cancer are elderly and have other serious "comorbid" medical conditions. Also note that many patients live high quality lives, often for years, with "incurable" cancer, if the symptoms are properly managed ("palliated").
What is the Conventional Treatment for Penile Cancer?
The Conventional Treatments
for penile cancer have been Radical Surgery for those who could tolerate it, and Radiation Therapy for those who were not "surgical candidates". Each of these is now described in detail:
Surgery
has been, and remains, the mainstay of treatment for penile cancer, and the treatment
to which other methods are compared for effectiveness. Surgery is ideally performed
by a "urologist" a Board-Certified specialty in operating upon teh urogenital tract. For early cancers
of the penile, the surgery is a straightforward "local excision"
which may even be done under local anesthesia at the time of biopsy. If the goal is
to remove the entire lesion, it must be accompanied by an appropriate "safety margin"
to account for cells that have migrated from the main tumor. When the biopsy specimen
is examined by the pathologist (s)he will state whether "clear margins"
were obtained-- that is no tumor cells are seen at the edge of the specimen. This
is obviously very important if local excision is to be the only therapy, for if "clear
margins" were not obtained, we can assume that residual cancer was left behind. The patient will then need to
undergo another surgery for "re-excision" to obtain clear margins. A main problem
with other methods of destroying early tumors, such as burning ("fulguration")
, freezing with nitrogen ("cryotherapy")
or electrically destroying them ("electrodessication") is that there is no pathological specimen to send to determine whether all the cancer was
removed
! Interestingly, even if some cells were left behind, this does not automatically
mean that the tumor will regrow, but it is very possible. Thus, "wedge biopsy"
which removes the entire lesion ("excisional biopsy") is the best choice for early penile cancers.
Very early cancers, or Carcinoma in Situ ("CIS") has almost zero chance of having spread to local lymph nodes in the groin ("inguinal nodes")
and so these nodes are not sampled unless they are enlarged. Also, local excision
is often enough for cancers invading the urethra near the tip of the penis ("distal urethra")
, since the chance of spreading to lymph nodes is small. However, as a cancer grows,
the chance of spread to local lymph nodes increases proportionately. If the cancer
is not removable with simple excisional biopsy, if it invades the urethral deeper
inside the penis ("proximal urethra")
or if lymph nodes in the groin are swollen ("lympadenopathy") then a more radical
procedure is needed-- including sampling of the local lymph nodes in the groin.
The more radical surgical procedure done on the penis is a "partial penectomy"
, which means cutting part of the penis off while under
general or spinal anesthesia. Since penile cancer is usually on the further end of
the penis ("distal penis") enough of the organ can often be retained to keep urinary and sexual function. Even
though the most sensitive area of the penis is the prepuce, erection and ejaculation
can [physically] still be achieved even when half of the penis is cut off. However,
psychological distress may lead to impotence. Besides the actual area of cancer, we
need a 2 cm. (~1 inch) "margin" of apparently normal surrounding tissue to be removed to help ensure the cancer does
not recurr.
When the disease is very "locally advanced"
, or on the portion of the penis closer to the pubis ("proximal penis") might "total penectomy"
-- complete removal of the penis-- be necessary. The remaining urethra is diverted
into an artificial opening made in the perineum-- that is the area between the scrotal
sac and anus. A man will have to sit to urinate if they have this "perineal urethrostomy" created. Obviously, sexual activity will be severely curtailed, but with modifications
some pleasure is still possible. About 50% of patients with locally advanced penile
cancer have enlarged and detectable ("palpable") lymph nodes in the groin on physical exam. However, the chance that these nodes actual contain cancer, when they are
biopsied, averages only 40% (since inflammation and infection can also enlarge them).
The approach to the patient with penile cancer and enlarged groin nodes is to give
a 4 to 6 weeks course of b antibiotics to see if the swelling completely disappears.
If it does not, we procede with an "inguinal lymph node dissection"
at surgery. About 50% of patients will actual spread to the groin lymph nodes can
be cured by this dissection. Even if the disease has spread upward into the iliac
and para-aortic nodes, some patients can still be cured by "surgerizing" these. A
CT scan with contrast of the abdomen will normally show whether these more distant lymph nodes
are enlarged. If the lymph nodes in the groin and pelvis are free of cancer, the
chance that the para-aortic nodes will be involved is less than 2%, and so we don't
treat for it. In general, for stage I disease we do not do a routine lymph node dissection.
For stage II it is controversial whether to do a "prophylactic" dissection (in the absence of any lymphadenopathy) or whether to wait to see if those
nodes eventually enlarge before doing anything to them. If they do enlarge, then
a "therapeutic" dissection will be done. For stage III or local IV disease, routine lymph node sampling
("sentinal node biopsy")
, if not outright dissection, is appropriate.
The reluctance to do a lymph node dissection in early disease is due to two facts--
the chance of involvement of the nodes with cancer is low, and the side-effects ("morbidity") from lymph node dissections can be high. About 1% of patients actually die from
the procedure. The main problem for other is death of overlying skin ("necrosis") in up to 20%, infection in 15%, and swelling of the lower limbs ("edema") which can
be permanent in 30%. This is especially likely if radiation therapy is added afterward.
Rare problems are bleeding ("hemorrhage")
, hernia, and chronic pain in the area. In general, surgery is an effective treatment
for localized penile cancer, and when used alone gives survivals similar to the historical
ones by stage stated above.
Radiation Therapy has been used for the past 8 decades for penile cancer, and it has
had many technical improvements in the past 2 decades. It is attractive to shine
a beam of photons on the cancer to kill it, rather than cutting off much (or all)
of the penis. The main advantages to radiation are the good chance of curing the cancer and
maintaining a functioning penis. Disadvantages include a lower control rate of large
local cancers than surgery (although surgery may be afterwards for salvage).
Like surgery, radiation therapy is a local treatment, but a wider "field"
may be radiated than removed surgically. As will be seen, it can be combined with
other therapies to increase "local control" of vulvar cancer , since return of vulvar area disease has been a major problem
for unsuccessfully treated patients. Radiation Therapy can also help relieve ("palliate") the symptoms caused by distant spread of the disease. Treatment is administered
under a "Radiation Oncologist"
, a cancer doctor who specializes in utilizing radiation.
Radiation kills cancer cells by damaging their DNA
, they die when they try to divide. Thus, damaged cancer cells die even after the
treatment is complete. Radiation will also kill normal cells, which limits the amount
that can be given.
However, it usually takes more radiation to kill normal cells than cancer cells, and
normal cells can often repair the radiation damage, while cancer cells can not. Nevertheless,
it is important to be as exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells. Particular areas
of concern when radiating the penis and groin include the rectum and small bowel and bladder
.
To receive therapy, a patient is first seen in "consult" by a radiation oncologist, who reviews the patient's medical record, complaints,
and radiology films. After explaining the possible benefits and side-effects of radiation,
the patient is scheduled for a "simulation". This means the area to be treated is marked out on a replica treatment machine,
and films are taken. Some barium contrast material is usually squirted up the patient's
rectum. Watercolor marks are painted on the patient to denote the treatment area,
and eventually small, permanent tattoos are placed on the skin. Sometimes the patient
is sent for a CT scan along with the simulation, the whole process takes less than
2 hours, and is painless. Information from the simulation and relevant scans is placed
into a "treatment planning computer"
, which generates a "plan". This plan tells how much radiation is going to the tumor area, and how much to adjoining
normal tissues. For penile cancer, particular attention is paid for how much radiation
is going to the bladder, rectum, and small intestine. The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior
to starting therapy. The patient then comes in for their "treatment start". They are placed on a hard, flat table in a specially shielded room and aligned with
laser lights.
The actual treatments are given by "Radiation Therapists"
, or "R.T.T's"
, who are first certified for diagnostic X-rays and then get additional training to
deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not tell anything about the cancer.
The actual treatment only takes a couple of minutes and is given with a Linear Accelerator (or occasionally older Cobalt-60) which precisely aims a beam of photons at the treatment
area. The head of the machine can swivel about the patient, to give the treatment
from different angles. The patient needs only to lie still. Areas that are not to
be treated can be "blocked"
with special lead-type blocks in the head of the treatment machine.
Normally, patients area treated 5 days a week, Monday through Friday, taking only
several minutes each day. The usual dose for penile cancer is 60 Gray (units of radiation)
given at 10 Gray per week. If a treatment is missed, it is simply tacked on to the
end so full prescribed dose it given. It is common to "cone down" off of the full pelvis after 50 Gray (since this is the tolerance dose for the small
bowel) and shrink the field to treat the penis
proper only. This is called a "boost". Be aware that treatment normally covers the major lymph nodes in the pelvis. To
cover the inguinal area properly, a pad material ("bolus") is often used to cover the groin;
will boost up the dose to the shallow tissues, important for full inguinal node coverage.
Alternately, the inguinals can be "boosted" up with a electron beam field, which
is less penetrating than the photons used to treat deeper tissues. Sometimes just
the penis itself is treated, in this case a wax mold may be made around it to keep it
upright, and it can be treated through and through with photons.
Alternately, for very small lesion to be radiated, "orthovoltage" machines can be used which aim lower energy radiation (~200 Kilovolts) directly at
the area, and the field can be shaped with lead cut by a scissors. The problem with
this is that it does nothing for possible groin lymph nodes or disease that has spread
up into the pelvis. Yet another possibility is to give "Brachytherapy"
, which means actually (temporarily) implanting a radioactive source (like Iridium
192 wire) into the lesion. The advantage of this is that a very high dose can be
given to a tumor, with minimal dose to surrounding normal tissues. Implants are commonly
left in place 3 to 5 days during which the patient is hospitalized in a specially shielded
room. The main disadvantage is that it is a very local treatment and does nothing
for spread of disease.
Radiation to the penis or pelvis area is painless, the patient does not become "radioactive", nauseated or lose their scalp hair. The patient can usually maintain normal activities, such as working, driving, and
intake of alcoholic beverages. The side-effects of External Beam treatments are
classified as "acute" (during treatment) or "late" (months to years after treatment). The most common acute symptoms are reddening of
the skin in the treatment area, and anal area irritation. After several weeks of
radiation therapy, it is common to develop frequent urination and diarrhea as the
bladder and rectum (respectively) become irritated. The physician should prescribe steroid
suppositories and anti-diarrheal medicine; this is usually all that's necessary to
treat these acute effects; some dietary modification (less fruit and fiber) may also
help. There is often a sense of greater fatigue while receiving radiation.
As the dose "builds up" with successive treatments, more blood in the urine may be seen. In general, however,
radiation treatments are very well tolerated
, the expected side-effects are confined to the treatment area, and abate after completion
of therapy. Of more concern are possible "late" effects, which tend to be long lasting or permanent if they occur. Specifically,
impotence develops in about 50% of irradiated patients, bladder constriction ultimately
requiring cystectomy in 10%, chronic diarrhea in 5%, and bowel or urethral obstruction requiring eventual surgery in 5%. Incontinence is rare (2%) as are second cancers
caused by radiation (<1%). For a properly designed filed, the scrotum should be relatively
protected but decrease in sperm production for at least 6 months is common. Rarely total sterility will result. Patients are advised not to impregnate a women for
at least 6 months after treatment to minimize the chance of a radiation caused genetic
mutation in the offspring. Giving the treatment as many fractions, instead of in one large dose, helps reduce
the incidence of late reactions. The patient returns for follow-up after completion
of treatments, seeing both their urologist and radiation oncologist. If all goes
well, they are ultimately seen once or twice yearly for routine check. Overall, radiation treatments are safer than surgery. The results of radiation therapy
alone for invasive penile cancer show about 60% of patients surviving 5 years-- which
is the same as surgery! This is especially remarkable since most of these patients have more advanced tumors or are medically sicker than surgical patients.
Radiation therapy may be used to shrink stage III and IVA tumors, to make them amenable
to surgical removal. When surgery has been performed first, and two or more inguinal nodes are involved,
post-operative radiation therapy reduces local recurrence and increases long-term
survival
. In this case the dose given is lower, 50 Gray, since we are only radiating for "microscopic residual" disease, all the "gross tumor"
having been removed surgically. If radiation does fail, then penectomy (possibly in
conjunction with lymph nodes removing procedures) can be considered for "salvage" and works about 25% of the time. In general, while the Acute Effects of radical
radiation may be hard to take, with a lot of anal, scrotal and perineal irritation,
the outcome is worth the temporary discomfort. Radiation is particularly effective
for Kaposi's Sarcoma of the penis and may be given in lower dose (~25 Gray). CancerAnswers has available an In-Depth Transcript about Radiation Therapy which may
be ordered through our Web Site.
Chemotherapy
is not curative alone for penile cancer, except when injections of chemotherapy "agents"
are given for Kaposi's sarcoma. For Squamous Cancers we require surgery and/or radiation
for "local control". However, these methods do nothing for "distant disease"
, it is [theoretically] possible for any cancer to spread at any time. The greater
the extent of local disease, the greater the chance that some tumor cells have "escaped"
and "seeded" to distant parts of the body, such as the liver and lung. Initially these "seeds"
will be too small to detect with any available test or scan, and are called "micro-metastasis". Ultimately, if not controlled they will grow into large tumors and kill the patient.
Chemotherapy is the best current way of "systemically"
treating penile cancer-- that means treating the entire body.
The most effective current chemotherapy to shrink epithelial tumors is cisplatin,
a derivative of platinum. Carboplatin can be substituted for patients who have weak
kidney function, since cisplatin is "nephrotoxic'- that is damaging to the kidneys.
At MD Anderson Cancer center, cisplatin was combined with methotrexate and mitomycin-- two
other potent chemotherapy drugs. Obviously, this type of treatment must be carefully
monitored by an expert "medical oncologist". The results showed a "response rate" of over 70%, but the average length of response was only 6 months. This is because
cancers develop resistance to chemotherapy much like bacteria do toward antibiotics.
However, it may be useful to get the tumor to shrink down enough to be operated on,
including lymph nodes in the groin that are large. Radiation can also be given to these
patients. Using all three methods ("multimodality") is the latest effective treatment for locally advanced penile cancer. Other drugs
that can be used include 5-Fluorouracil (5-FU), taxols, and bleomycin. The more drugs
used, the greater the response (in general) but also the more side effects ("toxicity")
-- so keen judgement on the part of the oncologist is required. The "MVAC" chemotherapy
used for bladder cancer was NOT effective when tried with penile cancer. Theoretically,
at least, any effective chemotherapy drug should reduce the later risk of "distant failure" in other body organs-- by killing the cancer "seeds" when they are smallest and easiest
to obliterate. Unfortunately, we don't expect today's chemotherapy to cure massive
distant disease, but it may help relieve ("palliate") its symptoms.
Latest Effective Treatment:
A relatively new treatment, AFTER APPROPRIATE EXCISIONAL SURGERY, is the use of Topical
(spread on the skin) 5% 5-Fluorouracil ("5-FU") cream. This is usually spread over the penis on seven consecutive days, with 3 treatment
"cycles" being at least 2 weeks apart. This "topical chemotherapy" vastly reduces the number of new vulvar cancers forming, and treats residual cancer
cells that were missed at surgery. It may irritate the area, but otherwise has no
appreciable body wide ("systemic") side effects, as it is only local treatment. Studies show it about 90% effective
at preventing recurrence, and the treatment may be repeated if necessary. This therapy
is only effective for squamous cell cancer or precancer, not for melanoma of the
penis.
For patients with deeper invasion of penilecancer, up to about 5 millimeters into
the skin, surgery remains the first choice A "radical local excision with bilateral
(i.e. both sides) inguinal lymph node dissection
" is done for any localloy advanced penile cancer in patients who can tolerate surgery.
If positive lymph nodes are found in the groin, it is appropriate to add extra ("adjuvant") radiation therapy to 50 Gray over 5 weeks to the groins and pelvis, both since pelvic
lymph nodes may be involved, and to reduce the recurrence risk in the groin. On the
other hand, radiation alone is NOT usually curative for disease larger than about
3 cm. in the groin-- the tumor needs to be "debulked" with surgery (either before or
after radiation). For patients who can't tolerate surgery, "primary radiation therapy"
with at least 60 Gray should be given to the cancer area (including the groin), but
the pelvic dose should be limited to 50 Gray to minimize Late Effects there. This
50 Gray is sufficient for mopping up "microscopic disease"
, but higher doses (i.e. 65 - 70 Gray in 7 weeks) are necessary for "gross disease". Since we cannot re-irradiate to these high levels, it is crucial to do it right
the first time with an expert radiation doctor.
For patients with stage II
or greater ("locally advanced")
penile cancer have been treated with either partial penectomy
or total penectomy
, with bilateral inguinal lymph node dissection. Patients who had massive local disease
got "exenteration" procedures, which means cutting out the bladder and prostate as well as the penis
and possibly scrotum. Using separate incisions to remove groin lymph nodes reduces
the risk of lower extremity swelling ("edema") and wound breakdown ("dehiscence"). The latest effective treatment for these patients is to use "combination pre-operative chemo-radiation"
to shrink the tumor, followed by radical local excision of any residual tumor and
"bilateral groin lymph node dissection". This "combination therapy" is the same strategy as has been used successfully for anal, vulvar and esophagus
cancers, it is available at University Academic Medical Centers. It should be administered
jointly by cooperation between the urologist
and radiation oncologist
. Insist upon proper specialists, and not "general surgeons" or "medical oncologists"
to the surgery and chemotherapy.
The chemotherapy agents commonly used for combined treatment are Intravenous 5-Fluorouracil, Mitomycin-C, and Adriamycin. These agents can cause lowering of blood counts, intense local irritation, nausea
and diarrhea, and baldness and heart damage (Adriamycin). CancerAnswers offers a much more In-Depth understanding of Chemotherapy is available
through our Web Site. We can extrapolate results for female vulvar cancer to penile cancer, since it
is basically the same counterpart tissue- and vulvar cancer is much more common in
the USA. Better results may be gotten with 5-Fluorouracil, the most popular agent,
if it is given slowly by "infusion pump" instead of in large injected doses ("bolus"). The results of chemo-radiation show: For locally advanced penile cancer, over 60% of patients appear cured in limited
series, and 50% of "salvage patients" (treated after failed surgery) stay free of
disease for long periods (years)
.
A common place for recurrence after surgery, especially in patients who did not receive
radiation, is the groin. This can lead to severe open wound problems with cancer
spreading on the skin, infection and pain. Radiation treatment with Hyperthermia means heating the area (to about 110 degrees F.) and then delivering radiation. If
External Beam with electrons or photons has already been given to the area, an "implant"
of radioactive material ("brachytherapy")
over several days may control the tumor, with minimal dose to surrounding normal tissues.
Also 5-Fluorouracil cream and Retinoic Acid cream (a vitamin "A' derivative) can be spread over the area to fight existing cancer and
minimize new cancer formation.
Treatment for Melanoma is discussed separately in a specialized transcript.
Relief of Symptoms ("Palliation"):
When penile cancer is Stage IV
, with distant spread through the body, the objective is no longer cure but symptom
relief ("palliation"). The patient should always be made as comfortable as possible,
and narcotic medicines like morphine (which Osler called "G-d's own medicine) should
never be withheld for fear of causing "addiction". Using "Fentanyl Patches"
applied to the skin helps give a continuous amount of narcotic, eliminating the problems
of forgotten doses, "loss" of narcotics, and smoothing out the dosing for less disturbing
"highs and lows". Importantly, Radiation Treatment can help pelvic pain, urinary obstruction, bleeding and bone pain in over 80% of patients. It is also useful
for reducing the symptoms, and even extending survival, in patients with spread to
the brain. Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the
spinal cord. Any patient with penile cancer who experiences new weakness of the extremities, numbness,
or loss of bowel or bladder function must be brought into the Emergency Room immediately
to see whether the tumor is compressing the spinal cord causing these symptoms
. Up to 60% of new back pain in a cancer patient is caused by spread of cancer there.
The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for
"epidural spinal cord compression". If this is caught early, and treatment is given, permanent paralysis may be prevented
It is sadly uncommon to reverse symptoms of paralysis once they have set it, however,
so quick recognition is essential.
Obviously, it is crucial to keep urine outflow going and many surgeries can be used to "divert" the urine into the bowel or a perineal
opening. A "bag" to collect it stationed on the abdomen may occasionally be necessary,
if continence is lost. Frequently a catheter (tube) can be put into a hole where the ureter exits and a "leg bag" of plastic can be used to collect urine. The muscle
which controls continence is on the membranous portion of the urethra, and if often
spared.
As mentioned, radiation treatment can be very helpful for metastatic penile cancer. A relatively new method of radiation
for spread to the brain is "Stereotactic Radiosurgery"
, where multiple beams of convergent radiation are aimed onto the area(s) of spread
in brain, in a single painless session of one afternoon. This is usually followed
by 10 to 20 treatments with conventional "External Beam" radiation. The advantage of Stereotactic Radiosurgery is that it can give a very
high dose of radiation to areas of brain metastasis, and possibly enhance survival
for these patients, without the risk of an open brain surgery from a neurosurgeon.
Other options for patients in severe pain for multiple areas of spread to bone include
"hemi-body" radiation, and "strontium-89". Hemi-Body radiation uses a low
dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple
areas of bony involvement; some anti-nauseants are usually necessary and it lowers
blood counts. It is over 90% effective for pain relief lasting an average of 6 months. Strontium-89 is an injected radioisotope that goes through the bloodstream to all
bony areas, and is especially attracted to cancerous areas. It also lowers blood
counts but is very effective at palliating pain. It can only be done once. If no
relief is gotten from medications or radiation, neurosurgical techniques to cut sensory nerves
can usually afford relief, to this small population of patients. Committing suicide
because of unrelieved pain should NEVER be necessary with pain science today.
The patient with newly diagnosed penile cancer should not rely on any one therapy,
but instead should use a combination approach to maximize the chance for success Specifically, besides the conventional medical
therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative
therapy that you believe in, a program of spiritual renewal, "mind over cancer',
nutritional therapy and exercise. Keep the most positive attitude possible-- research
has shown this to be an important factor in survival. CancerAnswers has a transcript available on reasonable alternative treatments which
you can order through our web-site. Using a true "multi-modality" approach will give the confidence that you have done everything possible for a happy
outcome, and certainly improve the current quality of life.
In conclusion, new techniques utilizing surgery, radiation therapy and chemotherapy
are showing better survival rates than ever before for penile cancer. If cure is
the objective, consider getting treatments at a University Academic Center and joining
ongoing research trials which offer the latest therapies. The National Cancer Institute
keeps a listing of open cancer trials on their website (they change frequently).
Especially look for ones listed as "Intergroup" studies, or in conjunction with the Radiation Oncology Therapy Group ("RTOG"). The future has never looked brighter for penile cancer patients!
This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Penile Cancer. Much more, including latest additional treatments for Penile Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.
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ADDITIONAL TOPICS
Acute Leukemia
Anal Cancer
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer: Early
Breast Cancer: Advanced
Cartilage Cancer
Cervical Cancer
Chronic Leukemia
Colo-rectal Cancer
Esophagus Cancer
Fat Cancer
Gall-Bladder Cancer
Hodgkin's disease
Kidney Cancer
Larynx Cancer
Liver Cancer
Lung Cancer
Lung "small cell" Cancer
Lymphoma
Melanoma
Mesothelioma
Mouth Cancer
Multiple Myeloma
Muscle Cancer
Muscle and Fat Tumors
Nasal Cavity Cancer
Nasopharynx Cancer
Ovarian Cancer
Pancreas Cancer
Penile Cancer
Plasmacytomia
Prostate Cancer
Skin Cancer
Stomach Cancer
Testicle Cancer
Thyroid Cancer
Tongue Base and Tonsil
Cancer of Unknown Origin
Uterine Cancer
Vaginal Cancer
Vulvar Cancer
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