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Testicular Cancer
191
Reference
Donohue JP, Zachary JM, Maynard BR. Distribution of nodal metastases in nonsemi-
nomatous testis cancer. J Urol. 1982;128(2):315.
9. Prognostic Factors
• Approximately 85% of pure seminoma is localized . Thus patients with pure
seminoma have a better prognosis than those with nonseminoma.
• For patients with seminoma tumor size (> 4 cm), rete testes invasion and vascular
invasion have been shown to be important for predicting relapse risk.
• According to the MRC staging system Retroperitoneal nodal size has been shown to
be associated with the risk of recurrence.
• for stage II seminoma the only prognostic factor described as independent prognostic
factors associatd with local recurrence is the bulk of the lymphadenopathy: Local
recurrence related with size could be approximately summarized as 6% for tumor (T)
< 3 cm, 18% for T = 3–6 cm, 36% for T > 6 cm.
• For non-seminomatous cancer the prognostic factors independently associated with
worse prognosis are; presence of liver, bone, or brain metastases: very high serum
markers, primary mediastinal nonseminoma, and large number of lung metastases.
Reference
Birch R, Williams S, Cone A, Einhorn L, Roark P, Turner S, Greco FA. Prognostic factors for
favorable outcome in disseminated germ cell tumors. J Clin Oncol. 1986;4(3):400.
10. Treatment
• Men with a suspected primary testicular cancer, should be submitted to orchiectomy
to establish the histologic diagnosis and definitive treatment.
• The standard surgical procedure for orchiectomy is a radical inguinal orchiectomy.
This surgical approach is through an inguinal incision to avoid interruption of
testicular lymphatics (figure-5).
• Active surveillance, adjuvant limited field radiation therapy (RT), or a short course
of adjuvant single agente carboplatin can be offered after orchiectomy for seminoma
clinical stage I.
• The choice among these therapy options needs a consideration of the patient's
cooperation to comply with a surveillance program as well as to evaluate the risk and
the benefits of adjuvant chemotherapy or adjuvant RT.
• Active surveillance after radical orchiectomy can be offered for patients with clinical
stage I seminoma who are willing and able to comply with an active surveillance
program.
Gustavo Arruda Viani
192
Study
Description
Fosså et al.
(1999)
478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal
operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients).
Median follow-up time was 4.5 years. The 3-year relapse-free survival was 96% after
PA radiotherapy and 96.6% after DL. Survival at 3 years was 99.3% for PA and
100% for DL radiotherapy.
Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced
in patients in the PA arm. The sperm counts were significantly higher after PA than
after DL irradiation.
Jones et al.
(2005)
Patients were randomly assigned 20 Gy/10 fractions over 2 weeks or 30 Gy/15
fractions.
625 patients were randomly assigned to treatment. With a median follow-up of 61
months, 10 and 11 relapses, respectively, have been reported in the 30- and 20-Gy
groups.
The absolute difference in 2-year relapse rates is 0.7%. Only one patient has died
from seminoma (allocated to the 20-Gy treatment group).
Oliver et al.
(2011)
1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n =
904).
RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT.
One death as a result of seminoma (in RT arm) occurred. Patients receiving at least
99% of the 7×AUC dose had a 5-year RFR of 96.1% compared with 92.6% in those
who received lower doses (P = .08).
• For patients with stage I seminoma with tumor size (> 4 cm), rete testes invasion and
vascular invasion can be treated by adjuvant radiotherapy or adjuvant chemotherapy.
• When adjuvant radiotherapy is the treatment option, radiotherapy fields including
paraaortic dranaige more than dog leg fields are recommended. In this sttings
radiotherapy doses of 20 Gy should be used (table-6)
Figure 5. Inguinal orchiectomy for testicular seminoma.
Table 6. Clinical evidence for adjuvant tretment for seminoma
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193
Study
Description
Classen et
al. (2003)
Patients with stages IIA/B disease (Royal Marsden classification) were assessable for
the trial. Radiotherapy was delivered to para-aortic and high ipsilateral iliac lymph
nodes. The total doses were 30 Gy for stage IIA and 36 Gy for stage IIB disease.
94 patients were included in that trial. Median time to follow-up was 70 months.
There were 66 stage IIA and 21 stage IIB patients.
Actuarial relapse-free survival at 6 years was 95.3% (95% confidence interval [CI],
88.9% to 100%) and 88.9% (95% CI, 74.4% to 100%) for stage IIA and IIB groups,
respectively.
Maximum acute side effects were 8% grade 3 nausea for stage IIA and 10% grade 3
nausea and diarrhea for stage IIB groups. No late toxicity was observed.
Chung et al.
(2004)
126 men with stage II seminoma were treated at Princess Margaret Hospital. Of
these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT).
At median follow-up of 8.5 years, 10-year overall survival was 93%, the 10-year
cause-specific survival was 94% and the 10-year relapse-free rates was 85%. Patients
with stage IIA and IIB disease treated with RT and stage IIB treated with
chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively.
Age, rete testis invasion and lymphovascular invasion were found not to be of
prognostic significance.
International
Germ Cell
Consensus
Collaborative groups from 10 countries provided clinical data on patients with
metastatic GCT treated with cisplatin-containing chemotherapy. Multivariate
analyses of prognostic factors for progression and survival were performed .
Data were available on 5,202 patients with nonseminomatous GCT (NSGCT) and
660 patients with seminoma.
Median follow-up time was 5 years. For seminoma, the predominant adverse feature
was the presence of NPVM. Integration of these factors produced the following
groupings: good prognosis, comprising 60% of GCT with a 91% (89% to 93%) 5year survival rate; intermediate prognosis, comprising 26% of GCT with a 79% (75%
to 83%) 5-year survival rate; and poor prognosis, comprising 14% of GCT (all with
NSGCT) with a 48% (42% to 54%) 5-year survival rate.
References
Fosså SD, Horwich A, Russell JM et al.. Optimal planning target volume for stage I testicular
seminoma: A Medical Research Council randomized trial. Medical Research Council
Testicular Tumor Working Group. J Clin Oncol. 1999;17(4):1146
Jones WG, Fossa SD, Mead GM et al. Randomized trial of 30 versus 20 Gy in the adjuvant
treatment of stage I Testicular Seminoma: a report on Medical Research Council Trial
TE18, European Organisation for the Research and Treatment of Cancer Trial 30942
(ISRCTN18525328). J Clin Oncol. 2005;23(6):1200.
Oliver RT, Mead GM, Rustin GJ et al. Randomized trial of carboplatin versus radiotherapy
for stage I seminoma: mature results on relapse and contralateral testis cancer rates in
MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011;29(8):95
• Low-dose RT to the paraaortic lymph nodes and superior ipsilateral pelvis (20 Gy)
followed by a small boost to the involved nodal áreas (25 Gy) is recommended for
patients with stage IIA/IIB seminoma.
• Cisplatin-based polychemotherapy is an option for patients in whom RT is not
feasible or for patients with bulky stage IIB/IIC seminoma. The preferred regimen in
this setting include three cycles of cisplatin, etoposide, and bleomycin (BEP) or four
cycles of etoposide platinum (EP), as showed in table-7.
Table 7. Clinical evidence for adjuvant treatment in stage II seminomas
Gustavo Arruda Viani
194
References
Classen J, Schmidberger H, Meisner C, Souchon R, Sautter-Bihl ML, Sauer R, Weinknecht S,
Köhrmann KU, Bamberg M. Radiotherapy for stages IIA/B testicular seminoma: final
report of a prospective multicenter clinical trial. J Clin Oncol. 2003;21(6):1101.
Chung PW, Gospodarowicz MK, Panzarella T, Jewett MA, Sturgeon JF, Tew-George B,
Bayley AJ, Catton CN, Milosevic MF, Moore M, Warde PR. Stage II testicular
seminoma: patterns of recurrence and outcome of treatment. Eur Urol. 2004;45(6):754.
International Germ Cell Consensus Classification: a prognostic factor-based staging system
for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J
Clin Oncol. 1997;15(2):594.
11. Radiotherapy Techniques
A CT scan of the abdomen is taken with the patient lying supine in the treatment position
with arms by his sides. The head and legs are restrained with head rest, ankle and knee
supports. Midline and lateral tattoos are used with laser lights to align the patient and prevent
lateral rotation.
Patients can be planned conventionally in a simulator, or using a CT scan for virtual
simulation of the fields, which gives information on the soft tissue anatomy, and position of
the renal pelvis.
For stage I, the CTV includes lymph node areas at high risk of microscopic involvement
i.e. para-aortic, renal hilar and retro-crural nodes bilaterally. Normal nodes are not visible on
CT scans but intravenous contrast can be used to enhance renal blood vessels to help locate
hilar nodes. If there has been previous scrotal surgery, the target volume also includes
ipsilateral pelvic and inguinal lymph nodes (identified by contrast enhanced pelvic blood
vessels).
Figure- xx a shows the “dogleg” field arrangement from the top of T11 (superior border)
to the top of the obturator foramen (inferior border). Figure- 6 demonstrates the paraaorticonly field arrangement from the top of T11 (superior border) to the bottom of L5 (inferior
border). Laterally, the field edge is placed at the tips of the transverse processes, which may
be expanded to include the left renal hilum for left-sided tumors.
Actually 20 Gy in 10 fractions is an acceptable dose for stage I seminoma. For stage IIA
and IIB the first PTV is treated with 20 Gy/10 fractions followed by a boost dose of 30-36 Gy
in larger lymph nodes.
Treatment with the dogleg field and the use of testicular shield, the contralateral
remaining testicle will receive about 1%–2% of the prescribed dose, which can lead to
temporary reduction in spermatogenesis and fertility. About half of the patients have subfertile sperm counts on presentation or after surgery. Fertility usually can be restored within
2–3 years in those who were fertile before radiotherapy. In this period the patients should be
advised to avoid fatherhood.
Testicular Cancer
195
Figure 6. Dog leg and paraortic fields for testicular seminoma.
Conclusion
• Testicular cancer is a highly curable cancer of young and middle-aged men.
• The overall survival of seminoma (all stages combined) exceeds 90%, and
approaches 100% for early-stage diseases.
• Radical inguinal orchiectomy is the standard procedure for diagnosis and treatment.
• Radiation or chemotherapy is the first option for adjuvant therapy in stage I low-risk
seminoma.
• High-risk stage I seminoma (tumor ≥4 cm or Rete testis invasion) and stage IIB
• cases (nodal disease <5 cm) should be treated for radiotherapy.
• For more extensive diseases (stage IIC or higher), chemotherapy is the treatment
choice for adjuvant therapy.
Section - IV. Hematology Cancer
Chapter 13
Non-Hodgkin’s Lymphoma
Introduction
Non-Hodgkin’s lymphoma (NHL) is considered a heterogeneous group of disease. The
majority of histological subtypes are of B-cell origin, with a wide variety of clinical
phenotypes. Chemotherapy is considered the mainstay for treating the majority of symptommatic presentations.
External-beam radiation therapy is an important treatment modality for limited, localized
indolent NHL, as well as in stage I and II aggressive tumors. This chapter will examine the
management of indolent and aggressive non-Hodgkin’s lymphoma.
1. Epidemiology
• NHL occurs with increasing frequency, with approximately 60,000 new cases
annually in the United States.
• The incidence is rising dramatically for unknown reasons. NHLs are the fifth and
sixth most common malignancy in men and women, respectively.
• The increase in incidence appears to be worldwide, with incidences ranging from
approximately 2 per 100,000 per year in Asia to 19 per 100,000 per year in the
United States.
• Data also suggest that the increase is greatest in the elderly and in diffuse large B-cell
lymphoma (DLBCL).
Gustavo Arruda Viani
200
Factor
Description
Altered immunologic states
Acquired immunodeficiency syndrome
Organ transplantation
Sjögren's syndrome
Rheumatoid arthritis
Inherited immune deficiencies
Viruses and bacteria
Human T-cell leukemia/lymphoma virus
Human immunodeficiency virus
Epstein-Barr virus
Human herpesvirus 8
Hepatitis C virus
H. pylori
Borellia
Chemical exposure
Agriculture chemicals
Wood products
Miscellaneous
Prior lymphomas
Part medical history
previous NHL, Hodgkin’s lymphoma,
other lymphoproliferative or hematopoietic malignancies,
basal cell or squamous cell skin cancers
Family history
twofold increase in risk for those who have
at least one 1st-degree relative with NHL
Reference
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10.
2. Risk Factors
Several risk factors have been determined for NHL and they are demonstrated in Table-1.
Table 1. Risk factors for NHL
Reference
Shipp MA, Mauch PM, Harris NL. Non-Hodgkin’s lymphomas. In DeVita VT Jr, Hellman S,
Rosenberg SA (eds): Cancer: Principles and Practice of Oncology, 5th ed. Philadelphia:
Lippincott- Raven, 1997, pp 2165-2220.
Lymph node regions were described for by Kaplan et al with staging purposes and have
been in use for over 40 years