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Healthcare
The management of testicular cancer in Victoria, 1988-1993
Guy C Toner, Greg J Neerhut, Max A Schwarz, Vicky J Thursfield, Thomas F
Sandeman, Graham G Giles and Ross M Snow, for the Urology Study
Committee of the Victorian Co-operative Oncology Group
MJA 2001; 174: 328-331
For editorial comment, see Boyer & Stockler
Abstract -
Methods -
Results -
Discussion -
Acknowledgements -
References -
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Objectives: To evaluate the patterns of care and
management of testicular cancer in Victoria.
Design and setting: Retrospective analysis of all cases
of testicular cancer in Victoria from 1988 to 1993 identified through
the Victorian Cancer Registry.
Main outcome measures: Description of patient
characteristics, staging investigations, initial management, and
outcome.
Results: 667 eligible cases of testicular cancer were
identified and questionnaires were returned for 633 of these
patients (94.9% response rate). There were 357 (56.4%) patients with
pure seminoma; 271 (42.8%) with non-seminomatous germ cell tumours,
3 (0.5%) with stromal tumours, and 2 (0.3%) with other tumours. The
median age was 32 years (range, 0-80 years). Preoperative marker
levels were not available for 8% of patients, and initial staging was
considered inadequate in 6%. Surveillance programs used for
patients with Stage I disease were considered inadequate in most.
Relative survival at five years was 99% for patients with seminoma and
91% for non-seminoma.
Conclusions: There was considerable variation in the
investigation, treatment, and follow-up of these patients, which is
likely to have resulted in unnecessary morbidity. Clinical practice
guidelines should be developed and implemented to promote optimal
management.
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Testicular cancer is uncommon but has a significant effect on the
community, as it typically develops in young men. The median age of
incidence is approximately 30 years.1 Excellent survival rates
are expected with the use of surgery, radiation therapy, and
chemotherapy.2 Cure is expected in about 80%
of patients with metastatic and relapsed disease.2
There is a strong evidence base available to guide management, with
relatively uniform practice at major centres internationally. Some
aspects of management are peculiar to this malignancy. These
include:
- the strong reliance on serum tumour markers
for management,3,4
- the use of surveillance in patients with Stage I disease, with
anticipated cure by salvage therapy in those who relapse,5
- the expectation of cure of metastatic disease with a brief,
intensive course of chemotherapy,6 and
- the use of surgery to resect residual masses at metastatic sites
after chemotherapy.7
Because of the potential for cure, the multidisciplinary nature of
management and the availability of high quality evidence to guide
practice, the management of testicular cancer is expected to provide
an excellent assessment of the quality of cancer management in a
community. However, there are no comprehensive data on the
management of testicular cancer in the community in Australia.
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Methods
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The Urology Study Committee of the Victorian Co-operative Oncology
Group undertook a survey of the management of testicular cancer in
Victoria. A population-based sample was identified from the cancer
registry. The period 1988 to 1993 was chosen to allow an adequate
sample size and follow-up for the survey. A questionnaire was
developed covering aspects of presentation, diagnosis, staging
investigations, therapy, and follow-up.
In January 1996, after approval by the Ethics Committee of the
Anti-Cancer Council of Victoria, the questionnaire was sent to the
treating doctors of all patients with testicular cancer in 1988-1993
identified in the cancer registry. Questionnaires were
subsequently sent to other doctors identified as participants in the
patients' care. Neither the doctors' nor the patients' names were
identified to third parties. At the end of the survey, the data were
entered into a database and a de-identified file was used for
analysis.
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Classification of testicular cancer | |
Germ cell tumours were classified as seminoma or non-seminoma.
Seminoma included only those cases with pure seminoma in the
histological specimens and a normal serum  -fetoprotein level.
Cases where any other histological component (such as embryonal
carcinoma, yolk sac or endodermal sinus tumour, choriocarcinoma, or
teratoma) was identified, or in which the serum -fetoprotein level
was elevated, were classified as non-seminoma.
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Analysis |
Analysis was conducted using the SPSS statistical
package8 for descriptive statistics
and  2
tests for significance of associations for categorical data.
Survival analysis was performed using the RelSurv Version
2.09
software package. First, relative survival proportions were
computed separately for each prognostic indicator. This method
adjusts the survival proportions for the other causes of mortality
associated with age using Victorian life-tables. Second, a
multivariate analysis (proportional hazards regression) was
performed, with variables entered stepwise into the regression
model in descending order of significance in the univariate
analyses. Improvement to the model was tested after each addition and
the variable was removed if the improvement was not significant
(P < 0.05).
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Quality of care |
In an attempt to assess the quality of care provided, a number of
performance measures were developed retrospectively by the working
group after review of the initial data analysis. All patients were
expected to have had preoperative measurement of serum
-fetoprotein and human chorionic gonadotropin levels. Adequate
staging investigations were considered to be computed tomography
(CT) scans of the abdomen and chest (or chest x-ray) for non-seminoma
and Stage II and III seminoma. Staging of Stage I seminoma was expected
to include the above or a lymphangiogram instead of the CT scan.
Adequate surveillance for Stage I non-seminoma was deemed to be at
least six measurements of tumour marker levels and four CT scans of the
abdomen in the first 12 months of follow-up. We arbitrarily defined
these performance measures, but we believe they represent
reasonable standards of care at the time of the study.
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Results
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There were 689 patients with testicular cancer identified in the
Victorian Cancer Registry for the six-year period 1988 to 1993. There
was a trend of increasing incidence, with the age-standardised
incidence per 100 000 men for the six consecutive years increasing
from 3.7 to 5.3, with an average annual rate of increase of 7.5%.
Twenty-two patients were excluded for reasons including residence
outside Victoria, diagnosis outside the study period, and incorrect
diagnosis.
Questionnaires were sent to the treating doctor for all 667 eligible
patients, and replies were received for 633 (94.9% response rate).
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Patient characteristics | |
Patient characteristics are shown in Box 1. There was a slight
predominance of seminoma. In most patients, disease was confined to
the testis at diagnosis; non-seminomas were more likely to present at
an advanced stage. There were 64 (10%) patients with cryptorchidism
and 2 (0.3%) with bilateral tumours at presentation.
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Location of care | |
The 633 patients were treated at 93 hospitals. Eighty-six of these
hospitals treated fewer than five patients with testicular cancer
per year, and 71 treated fewer than two per year. One hundred and
seventeen (19.4%) patients were managed exclusively at centres that
treated fewer than five patients with testicular cancer per year, and
111 patients (17.5%) were treated exclusively in private practice.
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Initial investigation | |
Staging investigations at diagnosis included abdominal CT scan in
591 men (93.4%), thoracic CT in 270 (42.7%), chest x-ray in 496
(78.4%), and lymphangiography in 234 (37.0%). There was a time trend
for less use of lymphangiography (P = 0.02) and greater use of
CT scanning of the chest (P = 0.005) during the period of the
survey.
An abdominal CT scan or lymphangiogram was not performed in 26
patients (4.1%), and a chest CT scan or chest x-ray was not performed in
33 (5.2%). Serum tumour markers were not measured at diagnosis in 16
patients (2.5%) and were recorded as "don't know" in 44 (7.0%).
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Management |
Initial management of the patients is shown in Box 2. Thirty-four
patients with seminoma and 103 patients with non-seminoma were
managed with surveillance. No patients were managed with primary
retroperitoneal lymph node dissection for Stage I or II
non-seminoma. Thirty-one (4.9%) patients did not receive initial
chemotherapy or radiation therapy and did not appear to enter an
active surveillance program.
There was considerable variation in the follow-up of patients on
surveillance, which was inadequate for many patients according to
our criteria. For patients with seminoma, investigations during the
first year of surveillance did not include an abdominal CT scan in 12
(36%), did not include a chest x-ray or chest CT scan in 17 (55%), and
included fewer than four serum tumour marker measurements in 25
(76%). Similarly, for patients with non-seminoma, no abdominal CT
scan was performed in the first year in 6 (6%), no chest imaging in 31
(30%), and fewer than four measurements of serum marker levels in 26
(26%).
Three of the 33 patients with seminoma managed with surveillance
relapsed, and one of these patients died. Twenty-seven of 102
patients with Stage I non-seminoma managed with surveillance
relapsed (one of whom died), with a median time to relapse of nine
months. Overall relative survival for these 102 patients was 99%.
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Survival |
Median follow-up was 87 months. The five-year relative survival
proportion for all men was 95% (95% CI, 94%-97%). There were
significant differences in survival according to histology, age,
and stage. These factors remained significant in multivariate
analysis (Box 3). There was no significant difference in survival by
date of diagnosis (1988-1990 v 1991-1993) or location of treatment
(categorised according to number of patients seen).
The relative survival according to tumour type and stage is shown in
Box 4. The relative survival at five years for patients with seminoma
(all stages) was 99% (95% CI, 98%-100%). For patients with
non-seminoma, relative survival at five years was Stage I, 98% (95%
CI, 97%-100%); Stage II, 92% (95% CI, 84%-100%); Stage III, 69% (95%
CI, 56%-82%). The overall relative survival for Stage II and III
patients was 84% (95% CI, 76%-91%).
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Quality of care |
Only 68% of patients completed all the quality-of-care measures that
we considered appropriate (Box 5). There was a correlation between
the successful completion of all measures and the number of cases
treated at an institution (P < 0.001; data not shown).
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Discussion | |
Many published series from major cancer treatment centres
internationally have demonstrated that excellent outcomes are now
the expected result of testicular cancer management. However, less
detailed information is available in population-based series. Our
survey was designed to assess management patterns and results in the
population of Victoria. The 94.9% response rate to the questionnaire
ensured that the results are representative of the entire community.
Studies in Scotland,10 Norway11 and New
York12 have indicated higher
survival proportions for patients treated in centres treating a
greater number of cases of testicular cancer compared with patients
treated in a "community" setting. A recently published clinical
trial performed in 49 European centres found the relative risk of
death was 1.85 (95% CI, 1.16-3.03) for patients with metastatic
poor-prognosis non-seminoma treated at centres entering fewer than
five patients on the study compared with those treated at centres
entering a greater number.13 We found that management
in Australia has been dispersed increasingly to many individual
clinicians and hospitals. In this series, testicular cancer was
managed in 93 centres; 71 of these centres treated fewer than two
patients per year, and 86 fewer than five per year. Yet, we did not find a
significant difference in survival between these centres and ones
that treated more patients.
Our results show a pleasing 95% relative survival of testicular
cancer patients when compared with a matched cohort from the same
population. Survival in other reported series includes a 95.7%
relative survival in the United States Surveillance, Epidemiology
and End Results (SEER) review for a similar time period,14 and a 99%
cancer-related survival in a community survey in southern
Norway.11 The stage at diagnosis and
survival outcomes in the SEER review are very similar to ours. The 69%
relative survival at five years for Stage III non-seminoma is lower
than expected. However, it is difficult to compare this figure with
published results, as not all details of prognostic
factors4 are available.
The 7.5% per year increase in incidence over the six-year period of the
survey is consistent with a continuation of the threefold increase in
Victoria between 1950 and 1980.15 Similar dramatic
increases in incidence have been reported in other Western
countries,1 but the cause remains
uncertain.16
Survival figures alone are an inadequate assessment of treatment.
The aim of management is to achieve cure with the least morbidity.
Patients who are initially managed poorly may be cured by salvage
therapy, but at the price of greater toxicity. The resulting
morbidity may be severe and potentially includes infertility,
sexual dysfunction, and an increased risk of secondary malignancy.
Our survey identified a number of problems. There was a wide variation
in patterns of practice, particularly in patients with early-stage
disease and those undergoing surveillance. Thirty-two per cent of
patients failed to complete five simple measures of quality of care.
More complex measures of quality of care, such as the extent of disease
at relapse after initial surveillance or the quality and type of
radiation therapy and chemotherapy, were not assessed in this
survey.
Surveillance after orchidectomy of Stage I seminoma, as an
alternative to radiation therapy, was initially described in
1988,17 but we did not consider it
to be accepted management during the period of the survey. Thus, we
were surprised by the number of Stage I seminoma patients managed by
surveillance. These patients were managed at multiple centres and
there is no evidence that they were entered into a clinical trial.
We were particularly concerned about inappropriate schedules for
follow-up when surveillance was initiated. Published results of
surveillance programs have emphasised the need for strict and
frequent follow-up and investigation to ensure that any relapse is
detected at an early stage.18 There are no published
data to indicate less rigorous programs of surveillance maintain the
same proportion of cure. Many patients with Stage I disease were also
lost to follow-up or refused therapy. Young men are often not well
motivated to continue regular and extensive follow-up. Therefore,
it is essential to ensure such patients are fully informed about the
options for therapy and the potential risk of unnecessary morbidity
and mortality if an appropriate program of management is not
followed.
We believe the development and implementation of management
guidelines for testicular cancer in our community may help to reduce
the problems we identified.
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Acknowledgements | |
We gratefully acknowledge the support of the Anti-Cancer Council of
Victoria, the Urological Study Committee of the Victorian
Co-operative Oncology Group, the Victorian Cancer Registry, and the
urologists and oncologists who participated in the survey and
completed the questionnaires.
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- McKiernan JM, Goluboff ET, Liberson GL, et al. Rising risk of
testicular cancer by birth cohort in the United States from 1973 to
1995. J Urol 1999; 162: 361-363.
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Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J
Med 1997; 337: 242-253.
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Bosl GJ, Geller NL, Cirrincione C, et al. Serum tumor markers in
patients with metastatic germ cell tumors of the testis. A 10-year
experience. Am J Med 1983; 75: 29-35.
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International Germ Cell Cancer Collaborative Group.
International Germ Cell Consensus Classification: a prognostic
factor-based staging system for metastatic germ cell cancers. J
Clin Oncol 1997; 15: 594-603.
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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 1992; 10: 1762-1768.
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Einhorn LH. Testicular cancer as a model for a curable neoplasm: the
Richard and Hinda Rosenthal Foundation Award Lecture. Cancer
Res 1981; 41: 3275-3280.
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Toner GC, Panicek DM, Heelan RT, et al. Adjunctive surgery after
chemotherapy for nonseminomatous germ cell tumors:
recommendations for patient selection. J Clin Oncol 1990; 8:
1683-1694.
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SPSS Inc. SPSS-X user's guide. 3rd ed. New York: McGraw-Hill; 1988.
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Hedelin G. RELSURV: a program for relative survival. Technical
report of the Department of Epidemiology and Public Health, Faculty
of Medicine. Strasbourg, France: Louis Pasteur University, 1995.
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Harding MJ, Paul J, Gillis CR, Kaye SB. Management of malignant
teratoma: does referral to a specialist unit matter. Lancet
1993; 341: 999-1002.
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Hernes EH, Harstad K, Fossa SD. Changing incidence and delay of
testicular cancer in southern Norway (1981-1992). Eur Urol
1996; 30: 349-357.
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Feuer EJ, Frey CM, Brawley OW, et al. After a treatment
breakthrough: a comparison of trial and population-based data for
advanced testicular cancer. J Clin Oncol 1994; 12: 368-377.
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Collette L, Sylvester RJ, Stenning SP, et al. Impact of the
treating institution on survival of patients with "poor-prognosis"
metastatic nonseminoma. European Organization for Research and
Treatment of Cancer Genito-Urinary Tract Cancer Collaborative
Group and the Medical Research Council Testicular Cancer Working
Party. J Natl Cancer Inst 1999; 91: 839-846.
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Ries LAG, Kosary CL, Hankey BF, et al. SEER cancer statistics
review, 1973-1996. Bethesda, MD: National Cancer Institute, 1999.
-
Stone JM, Cruickshank DG, Sandeman TF, Matthews JP. Trebling of
the incidence of testicular cancer in Victoria, Australia
(1950-1985). Cancer 1991; 68: 211-219.
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Bergstrom R, Adami HO, Mohner M, et al. Increase in testicular
cancer incidence in six European countries: a birth cohort
phenomenon. J Natl Cancer Inst 1996; 88: 727-733.
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Horwich A, Peckham MJ. Surveillance after orchidectomy for
clinical stage I germ-cell tumours of the testis. Prog Clin Biol
Res 1988; 269: 471-479.
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Boyer MJ, Cox K, Tattersall MH, et al. Active surveillance after
orchidectomy for nonseminomatous testicular germ cell tumors: late
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(Received 28 Jun, accepted 7 Nov, 2000)
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Peter MacCallum Cancer Institute, Melbourne, VIC.
Guy C Toner, MD, FRACP, Head, Medical Oncology;
Thomas F
Sandeman, MD ChB, FRACR, Radiation Oncologist.
Geelong Hospital, Geelong, VIC.
Greg J Neerhut, MB BS, FRACS(Urol), Urologist.
Alfred Hospital, Melbourne, VIC.
Max A Schwarz, MB BS(Hons), FRACP, Head, Medical Oncology
Unit;
Ross M Snow, MB BS, FRACS(Urol), Head, Urology Unit.
Anti-Cancer Council of Victoria, Melbourne, VIC.
Vicky J Thursfield, BSc, GradDip(Applied Stats),
Information Manager, Cancer Epidemiology Centre;
Graham G
Giles, PhD, Director, Victorian Cancer Registry.
Reprints will not be available from the authors.
Correspondence:
Associate Professor G C Toner, Head, Medical Oncology, Peter
MacCallum Cancer Institute, St Andrew's Place, East Melbourne, VIC
3002.
gtonerATpetermac.unimelb.edu.au
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| 1: Patient characteristics |
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Seminoma |
Non-seminoma |
Total* |
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| Number of patients |
357 |
271 |
633 |
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| Stage |
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| I (confined to testis) |
295 (83%) |
158 (58%) |
457 (72%) |
| II (retroperitoneal nodes) |
50 (14%) |
61 (23%) |
112 (18%) |
| III (more extensive) |
12 (3%) |
52 (19%) |
64 (10%) |
| Median age (range)† |
35 (17-80) |
27 (0-76) |
32 (0-80) |
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| * Includes three patients with
stromal tumours and two with "other" histology. † The difference in age
between men with seminoma and non-seminoma was significant (P<0.001). |
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| Back to text |
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| 2: Principal initial management after orchidectomy |
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Surveillance |
Radiation therapy |
Chemotherapy |
Other |
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| Seminoma (Stage) |
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| I (confined to testis) |
33 |
239 |
6 |
17 |
| IIa,b (RP nodes <5cm) |
1 |
25 |
6 |
1 |
| IIc,d (RP nodes >5cm) |
0 |
2 |
15 |
0 |
| III (more extensive) |
0 |
2 |
9 |
1 |
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| Non-seminoma (Stage) |
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| I (confined to testis) |
102 |
5 |
39 |
12 |
| II (RP nodes) |
1 |
0 |
60 |
0 |
| III (more extensive) |
0 |
0 |
52 |
0 |
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| Patients who received more than
one form of therapy (eg, radiation and chemotherapy) were classified to
the most significant form of treatment. Patients in the "other" category
were reported as lost to follow up, 7 (22.6%); refused therapy, 16 (51.6%);
received other therapy, 6 (19.4%); and not stated, 3 (9.7%). RP nodes=retroperitoneal
nodes. |
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| Back to text |
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| 3: Multivariate analyses of prognostic
factors for survival |
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Non-seminoma (n=266) |
All patients (n=633) |
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5-year survival |
RR (95% CI) |
P |
5-year survival |
RR (95% CI) |
P |
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| Morphology |
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| Seminoma |
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|
99% |
1.0 |
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| Non-seminoma |
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|
91% |
6.2 (1.9-20.0) |
<0.001 |
| Other |
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65% |
51.9 (8.5-319) |
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| Age |
|
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| <30 years |
93% |
1.0 |
|
96% |
1.0 |
|
| 30-49 years |
92% |
1.4 (0.5-3.6) |
0.039 |
98% |
1.5 (0.6-3.7) |
0.002 |
 50
years |
61% |
6.0 (1.9-19.3) |
|
78% |
9.8 (4.4-32.0) |
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| Stage |
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| I |
98% |
1.0 |
|
99% |
1.0 |
|
| II |
92% |
3.6 (0.8-17.0) |
<0.001 |
96% |
2.4 (0.7-8.6) |
<0.001 |
| III |
69% |
15.3 (4.4-52.8) |
|
73% |
11.9 (4.4-32.0) |
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| Multivariate analysis of survival for seminoma
was not appropriate given the small number of deaths in this group. RR=relative
risk. |
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| Back to text |
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| Back to text |
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| 5: Measures of quality of
care |
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| Measure |
Eligible |
Completed |
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| Preoperative measurement of tumour markers |
633 |
584 (92%) |
| Adequate staging investigations |
633 |
595 (94%) |
| Radiation therapy for Stage I seminoma |
295 |
239 (81%) |
| Appropriate surveillance for |
|
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| Stage I non-seminoma |
102 |
22 (22%) |
| Chemotherapy for Stage IId, III seminoma |
|
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| and Stage II, III non-seminoma |
132 |
127 (96%) |
| All of the appropriate measures |
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| completed in each case |
633 |
430 (68%) |
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| Back to text |
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