Transcript Diapositiva 1 - University of Cagliari

TUMORI DEL TESTICOLO
Pathology:
Seminoma
Pure seminoma accounts for 47% of all testis cancer patients (50% of patients
with cryptorchidism have seminoma). More than 90% of the cases of pure
seminoma are of the subtype called classic. These patients usually present
with disease in the fourth or fifth decade.
Approximately 75% of them present with stage I disease. Such patients may
have modest elevations of serum beta -human chorionic gonadotropin (beta HCG). It is worth noting that any elevation of alpha-fetoprotein connotes the
presence of nonseminomatous germ cell tumor.
Spermatocytic seminoma accounts for 7% of all seminomas. The median age
of presentation is in the sixth and seventh decade of life.
Because metastases are extraordinarily rare, orchiectomy is the only required
treatment.
Pathology: Non seminomatous Germ Cell Tumors
Embryonal carcinoma
Choriocarcinoma
Yolk sac carcinoma
Teratoma
Staging of GCTs
• Stage I – Testis only, T1
• Stage II – T2-4, vascular or lymphatic
invasion present
– Stage IIA – nodes <2 cm
– Stage IIB – nodes 2-5 cm
– Stage IIC – nodes >5 cm
• Stage III – Distant metastases
Primary Germ Cell Tumors of the
testis
• Usually present with painless testicular mass
– Retroperitoneal mets can cause back pain
– Pulmonary mets can cause dyspnea
• Initial test if suspicious for malignancy
- testicular ultrasound
• Staging CT of abd/pelvis, chest if X-ray
abnormal
Diagnosis- Ultrasound.
Most patients with testicular cancer present
with a painless scrotal mass. This mass may
be confused with epididymitis, particularly
when pain is noted. Careful attention on physical examination, should
generally discern a testicular mass from epididymitis.
Testicular ultrasound will confirm the findings.
Translumination of the testis may determine if the patient has a hydrocele;
however, about 20% of patients with germ cell tumors of the testis will have
a hydrocele. Testicular ultrasound is one of the most useful tools to evaluate
a testicular mass. Findings reveal solitary or multiple hyperechoic lesions.
Small areas of speckled calcifications suggest carcinoma in situ. Over 95%
of patients with testicular mass will have malignant pathology.
Presenting signs of testicular cancer.
Patients with retroperitoneal spread of tumor may present with back pain,
usually in the lumbar region. Further lymphatic spread to supraclavicular
lymph nodes (Virchow’s node) have also be seen.
Patients with advanced pulmonary disease may have cough, shortness of
breath, and hemoptysis.
Disease spread to the central nervous system and bone is rare; thus,
routine screening by radiograph or radionuclide scans is unnecessary in the
absence of symptoms.
Some patients present with gynecomastia. Although common in
adolescents, new onset of gynecomastia in young adults should suggest germ
cell malignancy or other endocrine abnormalities
Diagnosis and treatment are closely tied.
The preferred approach in a patient with a testicular mass
is a radical orchiectomy using the inguinal approach.
Fine-needle aspiration or trans-scrotal biopsy is
contraindicated because they can cause aberrant spread
of tumor to inguinal and iliac lymph node chains.
Chest radiography should be performed to rule out the
possibility of pulmonary disease.
If negative, CT of the chest should be performed.
An abdominal CT scan should be done
to evaluate the retroperitoneal
lymph nodes.
Serum beta -human chorionic gonadotropin ( beta-HCG)
and alpha-fetoprotein (AFP) levels
are elevated in about 85% of the patients with
disseminated germ cell tumor.
These markers are useful diagnostically and
therapeutically.
In a patient with pathologic stage I testicular cancer, an
orchiectomy should result in the reduction of serum HCG
and AFP levels according to their half lives (1 day and 5
days, respectively).
During treatment with chemotherapy, at least a one log
reduction of serum beta-HCG should occur every 3 weeks.
Patients with elevated AFP have a less predictable decline.
EARLY STAGE DISEASE
Radiation therapy
Radiation therapy is usually used in patients with
seminoma who have stage I or early stage II disease.
Most patients with stage I seminoma can be successfully
treated with the total dose of 2500 to 3500 cGy to a target area,
which includes the periaortic region from approximately the 11th
thoracic vertebrae to the lumbar region and extends to the
ipsilateral hemipelvis to include external iliac lymph nodes.
Routine radiation to the orchiectomy scar or to the testis is not
routinely performed. Bulky stage II disease is usually treated
with moderately higher dosages of 35 to 40 cGy or alternatively
with systemic chemotherapy.
EARLY STAGE DISEASE
Surgery
Retroperitoneal lymphadenectomy.
Retroperitoneal surgery for metastatic testis cancer consists of two primary
operations. In low stage disease, a modified template of dissection is used
contingent upon the side of the primary tumor.
Hence, the field of dissection for
a right-sided testicular tumor
includes the right paracaval
and interaortocaval regions.
For a left testicular primary,
the field includes the left
periaortic and preaortic lymphatics.
The ipsilateral sympathetics are
preserved to guarantee maintenance
of emission and ejaculation
postoperatively
EARLY STAGE DISEASE
Surgery
For early-stage (clinical stage I, IIa or IIb)
nonseminomatous germ cell tumor,
retroperitoneal lymphadenectomy
has been the mainstay of treatment for most of the past
century.
The success of surgery has been predicated on the
observation that testis cancer travels at a predictable
pattern from the testis to the retroperitoneum before
developing systemic metastases. Surgical operations have
evolved from a variety of templates to minimize
complications of retrograde ejaculation.
Year 1
Physical examination
Chest radiography PAL (q 1 mo)
Serum
-HCG/AFP (q 1 mo)
Abdominal CT scan (q 2 mo)
Year 2
Physical examination (q 2 mo)
Chest radiography PAL (q 2 mo)
Serum
-HCG/AFP (q 2 mo)
Abdominal CT scan (q 4 mo)
Years 3-5
Physical examination (q 6 mo)
Chest radiography PAL (q 6 mo)
Serum
-HCG/AFP (q 6 mo)
Abdominal CT scan (year 3 and 4 only)
After year 5 (annually)
Physical examination
Chest radiography PAL
Serum
-HCG/AFP
Surveillance Schedule
For patients with low-volume disease (3 cm in cross-sectional
diameter) and normal (or within predicted half life) serum markers,
the primary retroperitoneal lymph node dissection (RPLND) is preferred
treatment. In such patients, RPLND will result in cures of approximately
70%, without additional therapy.
In patients with completely resected disease but with metastasis to
lymph nodes, adjuvant chemotherapy can be considered. Two cycles of
BEP (bleomycin, etoposide, Platinol) in such patients should reduce the
relapse rate to around 1%. If observed without adjuvant therapy,
approximately 30% of patients have recurrence, but three cycles of BEP
should produce virtually a 100% cure rate for those with relapsing
disease.
For patients with rising markers following orchiectomy or with
retroperitoneal disease greater than 3 cm in cross-sectional diameter
(clinical stage B2 disease), primary chemotherapy is indicated.
In the absence of disease above the diaphragm and with serum beta-human
chorionic gonadotropin and alpha-fetoprotein below 5000 IU/L and 1000
ng/mL, respectively, three cycles of BEP or four cycles of EP (etoposide,
Platinol) are standard therapy.
BEP (bleomycin, etoposide, Platinol)
for treatment of stage C disease
Patients with disseminated disease are treated with cisplatin-based
combination chemotherapy. As mentioned earlier, various staging systems
have been used over the years to categorize patients with disseminated
germ cell tumors. Patients with good-risk disease can be treated with
three cycles of BEP or four cycles of EP (etoposide, Platinol). In a
recent randomized, prospective trial, no therapeutic differences were
observed between the two regimens, with slightly greater hematologic
toxicity associated with the four cycles of EP.
For patients with intermediate and advanced disease, the cure rate is
lower. As such, these patients are candidates for potentially more
aggressive therapy. The standard treatment approach is four cycles of
BEP. For patients with underlying pulmonary disease, substitution of
ifosfamide for bleomycin (VIP) is reasonable. VIP therapy has an
equivalent therapeutic outcome to BEP, but has slightly greater
hematologic toxicity.
Postchemotherapy retroperitoneal lymph node
dissection (RPLND).
RPLND is another operation for metastatic testicular tumors. This
procedure is performed for residual retroperitoneal tumor after
administration of chemotherapy for metastatic testis cancer.
The metastatic tumor can be very adherent to the great vessels and other
structures; thus, proper tissue planes are difficult to determine.
Specialized vascular techniques are sometimes necessary to completely
resect the retroperitoneal tumor, but complete resection of all tumor is
essential to ensure a good outcome.
Results of studies on salvage therapy
Salvage therapy is indicated for patients who relapse from complete
remission or who have an incomplete partial response to primary
chemotherapy. Ifosfamide salvage therapy. VeIP (vinblastine, ifosfamide,
and cisplatin) produces durable complete remissions in about 25% to
30% of patients with recurrent nonseminomatous germ cell tumor
(NSGCT) treated with second-line therapy. In patients with recurrent
seminoma, VeIP chemotherapy will produce durable complete
remissions in approximately 50% of patients. High-dose chemotherapy
with carboplatin and etoposide with peripheral stem cell rescue will
produce durable complete remissions in approximately 50% of patients
as second-line therapy. For patients with relapsing NSGCT, this is
preferred in salvage therapy. Patients who are candidates for salvage
therapy have mixed prognostic factors. Patients with pure seminoma or
longer relapse-free intervals (but < 2 years) have better prognosis than
those patients whose tumors progress on cisplatin, multiple regimens, or
mediastinal primary tumors.