Stage I Testicular Cancer
Stage I Seminoma
Stage I Nonseminoma
Current Clinical Trials
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Stage I Seminoma
Stage I seminoma has a cure rate of greater than 95% regardless of whether or not postorchiectomy adjuvant therapy is given.
Standard treatment options:
- Radical inguinal orchiectomy with no retroperitoneal node radiation therapy followed
by frequent determination of serum markers, chest x-rays, and computed tomographic (CT) scans
(surveillance). Results of multiple clinical series, with more than 900
patients with stage I seminoma managed by postorchiectomy surveillance, have
been reported.[1-3] The overall tumor recurrence rate is 15% to 20%, and nearly
all patients whose disease recurred were cured by radiation therapy or
chemotherapy. Thus, the overall cure rate is indistinguishable from that
achieved with adjuvant radiation therapy. Relapses after 5 years are unusual but can occur.[3]
- Radical inguinal orchiectomy followed by single-dose carboplatin adjuvant therapy. In a large randomized controlled equivalency trial comparing para-aortic (or dog-leg field, if clinically indicated) radiation to a single dose of carboplatin (concentration-versus-time curve [AUC] × 7) after radical inguinal orchiectomy, relapse-free survival (RFS) and overall survival (OS) rates were equivalent after a median follow-up of 4 years.[4][Level of evidence: 1iiA]
- Removal of the testicle via radical inguinal orchiectomy followed by radiation
therapy. Many radiation therapists recommend prophylactic radiation of the
retroperitoneal nodes even with a negative lymphangiogram and/or CT scan because approximately 15% of the patients will have occult nodal spread
that can be cured with radiation therapy.[5,6] Relapse rates and toxic effects were studied in a randomized
comparison in the MRC-TE08 trial, for example, of para-aortic radiation therapy alone versus para-aortic radiation
therapy with an added ipsilateral iliac lymph node field.[7] Three-year
RFS rates were virtually identical (96% vs. 96.6%) as
were OS rates (99.3% vs. 100%). Pelvic RFS
rates were 98.2% versus 100%; the 95% confidence interval (CI) for the difference in
pelvic RFS rates was 0% to 3.7%. A statistically
significant increase was observed in leukopenia and diarrhea associated with the ipsilateral
iliac radiation therapy. Patients with tumors with vascular invasion seem at
higher risk for nodal metastases.[8] In a randomized trial (EORTC-30942), radiation to 20 Gy over 10 daily fractions was clinically equivalent to 30 Gy over 15 fractions after a median follow-up of 61 months in both RFS and OS. Patient-reported lethargy and ability to perform normal work were better in the lower-dose regimen.[9][Level of evidence: 1iiA]
Stage I Nonseminoma
Stage I nonseminoma is highly curable (>95%). If preservation of fertility is
an important consideration, a surgical technique for sparing sympathetic
ganglia and chains should be used. This technique is associated with
postoperative fertility in most patients and appears to be as effective as
non-nerve-sparing procedures in preventing retroperitoneal relapse.[10]
Retroperitoneal dissection of lymph nodes is not helpful in the management of
children, and potential morbidity of the surgery is not justified by the
information obtained.[11]
Standard treatment options:
- Removal of the testicle through the groin followed (in adults) by
retroperitoneal lymph node dissection (RPLND) . A nerve-sparing RPLND that preserves ejaculation in virtually every patient has
been described in clinical stage I patients and appears to be as effective as
the standard RPLND dissection.[10,12] Surgery should be followed by monthly
determination of serum markers and chest x-rays for the first year and 1- to 2-month determinations for the second year.[13,14] In patients with pathologic stage
I disease after RPLND, the presence of lymphatic or venous invasion in the
primary tumor appears to predict for relapse.[15] In a large Testicular Cancer
Intergroup Study, the relapse rate was 19% in those with vascular invasion
versus 6% in those without vascular invasion. Retroperitoneal dissection of
lymph nodes is not helpful in the management of children, and potential
morbidity of the surgery is not justified by the information obtained.[11] In
a large study, 27% of clinical stage I tumors had metastatic involvement of
removed lymph nodes and were upstaged to pathological stage II.[16]
Chemotherapy is employed immediately on first evidence of recurrence. In a
large study, 15% of patients with a negative lymph node dissection experienced
recurrence, which was usually pulmonary and usually within 18 months.[16]
- Radical inguinal orchiectomy with no RPLND
followed by regular history (e.g., every 1–2 months), physical examination,
determination of serum markers, and, during the first year, abdominal CT scan
(surveillance).[2] Intervals for abdominal CT scans have varied from every 2
months to scans at 3 months and 12 months postorchiectomy with apparently similar
outcomes .[2,17][Level of evidence: 1iiA] Disease recurrence is rarely detected
by chest x-ray alone, so chest x-ray may play little or no role in routine
surveillance.[18] Long-term follow-up is important since relapses have been
reported more than 5 years after the orchiectomy in patients who did not
undergo a retroperitoneal dissection.[19-21]
This option should be considered only if:
- CT scan and serum markers are negative. Lymphangiography, when CT scan and
serum markers are negative, does not appear to significantly add to patient
management.[22]
- The patient and physician accept the need for repeat CT scans as necessary
to continue the periodic monitoring of the retroperitoneal lymph nodes.
Children are adequately followed by serum markers alpha-fetoprotein (AFP),
chest x-rays, and clinical examination.[11]
- The patient will diligently follow a program of regular checkups for 2 years,
which includes history, physical examination, x-ray of abdominal lymph nodes,
and determination of serum markers.
- The physician accepts responsibility for seeing that a follow-up schedule is
maintained as noted for 2 years and then periodically beyond 2 years.
- Adjuvant
therapy consisting of two courses of cisplatin, bleomycin, and etoposide in patients with clinical stage I disease who are considered at high
risk of relapse (about 50% predicted relapse rate based on presence of vascular
invasion and histologic type).[23] In 114 such patients, the RFS at 2 years was 98% (lower bound of 95% CI, 95%).
Another study of high-risk clinical stage I patients treated with two adjuvant
courses of cisplatin, etoposide, and bleomycin has been reported.[24]
Relapse rates after chemotherapy are less than 5% compared with about 50% in
historical series of high-risk patients followed without adjuvant chemotherapy.
In the historical series, however, cure rates have been 95% or more after
chemotherapy for relapse. It is unclear which approach is superior in outcome.
The adjuvant chemotherapy series is too small to draw conclusions about the
risk of chemotherapy-induced secondary malignancies, impact on fertility, or
risk of late relapse.
Data suggest that relapse rates are higher in patients with histologic evidence
of lymphatic or venous invasion and lower when the primary tumor contains
mature teratoma.[25] Some investigators have reported higher relapse rates in
patients with embryonal cell histology and recommend RPLND for such
patients.[16,26] Other investigators have not found a higher relapse rate for
this subgroup.[25,27] Additionally, some investigators recommend RPLND in
patients with a normal preorchiectomy AFP [16,26] because they feel the marker
cannot be used as an indicator of relapse during follow-up. Since
marker-negative patients may be marker-positive at relapse, and marker-positive
patients may be marker-negative at relapse, some investigators do not view a
negative AFP as a contraindication to a surveillance policy.[27]
A single course of cisplatin, bleomycin, and etoposide has also been given to clinical stage I patients with good results.[28] In a multicenter trial, 382 patients were randomly assigned to chemotherapy versus RPLND. The 2-year recurrence-free rates were 99.5% versus 91.9% (absolute difference 7.6%; 95% confidence interval 3.1% to 12.1%). There were no treatment-related or cancer-specific deaths in either arm of the study.[28][Level of evidence 1iiD]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Gospodarwicz MK, Sturgeon JF, Jewett MA: Early stage and advanced seminoma: role of radiation therapy, surgery, and chemotherapy. Semin Oncol 25 (2): 160-73, 1998.
[PUBMED Abstract]
-
Francis R, Bower M, Brunström G, et al.: Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options. Eur J Cancer 36 (15): 1925-32, 2000.
[PUBMED Abstract]
-
Choo R, Thomas G, Woo T, et al.: Long-term outcome of postorchiectomy surveillance for Stage I testicular seminoma. Int J Radiat Oncol Biol Phys 61 (3): 736-40, 2005.
[PUBMED Abstract]
-
Oliver RT, Mason MD, Mead GM, et al.: Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet 366 (9482): 293-300, 2005 Jul 23-29.
[PUBMED Abstract]
-
Stutzman RE, McLeod DG: Radiation therapy: a primary treatment modality for seminoma. Urol Clin North Am 7 (3): 757-64, 1980.
[PUBMED Abstract]
-
Duchesne GM, Horwich A, Dearnaley DP, et al.: Orchidectomy alone for stage I seminoma of the testis. Cancer 65 (5): 1115-8, 1990.
[PUBMED Abstract]
-
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 17 (4): 1146, 1999.
[PUBMED Abstract]
-
Marks LB, Rutgers JL, Shipley WU, et al.: Testicular seminoma: clinical and pathological features that may predict para-aortic lymph node metastases. J Urol 143 (3): 524-7, 1990.
[PUBMED Abstract]
-
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 23 (6): 1200-8, 2005.
[PUBMED Abstract]
-
Foster RS, McNulty A, Rubin LR, et al.: The fertility of patients with clinical stage I testis cancer managed by nerve sparing retroperitoneal lymph node dissection. J Urol 152 (4): 1139-42; discussion 1142-3, 1994.
[PUBMED Abstract]
-
Huddart SN, Mann JR, Gornall P, et al.: The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.
[PUBMED Abstract]
-
Foster RS, Donohue JP: Surgical treatment of clinical stage A nonseminomatous testis cancer. Semin Oncol 19 (2): 166-70, 1992.
[PUBMED Abstract]
-
Lange PH, Narayan P, Fraley EE: Fertility issues following therapy for testicular cancer. Semin Urol 2 (4): 264-74, 1984.
[PUBMED Abstract]
-
Williams SD, Einhorn LH: Clinical stage I testis tumors: the medical oncologist's view. Cancer Treat Rep 66 (1): 15-8, 1982.
[PUBMED Abstract]
-
Sesterhenn IA, Weiss RB, Mostofi FK, et al.: Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study. J Clin Oncol 10 (1): 69-78, 1992.
[PUBMED Abstract]
-
Klepp O, Olsson AM, Henrikson H, et al.: Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group. J Clin Oncol 8 (3): 509-18, 1990.
[PUBMED Abstract]
-
Rustin GJ, Mead GM, Stenning SP, et al.: Randomized trial of two or five computed tomography scans in the surveillance of patients with stage I nonseminomatous germ cell tumors of the testis: Medical Research Council Trial TE08, ISRCTN56475197--the National Cancer Research Institute Testis Cancer Clinical Studies Group. J Clin Oncol 25 (11): 1310-5, 2007.
[PUBMED Abstract]
-
Sharir S, Jewett MA, Sturgeon JF, et al.: Progression detection of stage I nonseminomatous testis cancer on surveillance: implications for the followup protocol. J Urol 161 (2): 472-5; discussion 475-6, 1999.
[PUBMED Abstract]
-
Rørth M, Jacobsen GK, von der Maase H, et al.: Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group. J Clin Oncol 9 (9): 1543-8, 1991.
[PUBMED Abstract]
-
Sujka SK, Huben RP: Clinical stage I nonseminomatous germ cell tumors of testis. Observation vs retroperitoneal lymph node dissection. Urology 38 (1): 29-31, 1991.
[PUBMED Abstract]
-
Sturgeon JF, Jewett MA, Alison RE, et al.: Surveillance after orchidectomy for patients with clinical stage I nonseminomatous testis tumors. J Clin Oncol 10 (4): 564-8, 1992.
[PUBMED Abstract]
-
Wishnow KI, Johnson DE, Tenney D: Are lymphangiograms necessary before placing patients with nonseminomatous testicular tumors on surveillance? J Urol 141 (5): 1133-5, 1989.
[PUBMED Abstract]
-
Cullen MH, Stenning SP, Parkinson MC, et al.: Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report. J Clin Oncol 14 (4): 1106-13, 1996.
[PUBMED Abstract]
-
Pont J, Albrecht W, Postner G, et al.: Adjuvant chemotherapy for high-risk clinical stage I nonseminomatous testicular germ cell cancer: long-term results of a prospective trial. J Clin Oncol 14 (2): 441-8, 1996.
[PUBMED Abstract]
-
Alexandre J, Fizazi K, Mahé C, et al.: Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse. Eur J Cancer 37 (5): 576-82, 2001.
[PUBMED Abstract]
-
Read G, Stenning SP, Cullen MH, et al.: Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J Clin Oncol 10 (11): 1762-8, 1992.
[PUBMED Abstract]
-
Colls BM, Harvey VJ, Skelton L, et al.: Results of the surveillance policy of stage I non-seminomatous germ cell testicular tumours. Br J Urol 70 (4): 423-8, 1992.
[PUBMED Abstract]
-
Albers P, Siener R, Krege S, et al.: Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol 26 (18): 2966-72, 2008.
[PUBMED Abstract]
Back to Top
< Previous Section | Next Section > |