Open Journal of Urology, 2011, 1, 50-55
doi:10.4236/oju.2011.13011 Published Online August 2011 (
Copyright © 2011 SciRes. OJU
Meta-Analysis to Determine the Diagnostic Value of
2-18Fluoro-2-Deoxy-D-Glucose Positron Emission
Tomography in Assessing Residual Tumors after Systemic
Therapy for Metastatic Seminoma
Johannes Mueller1, Thomas Schnoeller1, Friedemann Zengerling1, Sandra Waalkes2,
Andreas Al Ghazal1, Florian Jentzmik1, Mark Schrader1, Andres Jan Schrader1
1Department of Ur ol o gy, University Medical Center Ulm, Ulm, Germany
2Department of Ur ol o gy, MH Hannover, Hannover, Germany
E-mail: johannes.mueller@uniklinik-u
Received June 5, 2011; revised July 1, 2011; accepted July 10, 2011
Background: A meta-analysis was performed to determine the value of 2-18fluoro-2-deoxy-D-glucose posi-
tron emission tomography (FDG-PET) for assessing viable tumor residuals after chemotherapy in patients
with pure seminoma. Materials and methods: This review included five studies published between 1999 and
2010 with a total of 130 patients who underwent both computed tomography (CT) and FDG-PET scanning
for residual tumor detection after systemic therapy. We compared the sensitivity and specificity of FDG-PET
and CT (tumor size or > 3 cm) in identifying vital tumor tissue. Results: On the average, FDG-PET had
higher specificity (92% vs. 59%) and sensitivity (72% vs. 63%) as well as a higher positive predictive value
(PPV) than the solely size-based CT assessment of residual tumors (70% vs. 28%). PET also tended to have
a higher negative predictive value (93% vs. 86%). Conclusion: The present evaluation of currently available
data indicates that FDG-PET is superior to CT in detecting viable tumor residuals after chemotherapy in pa-
tients with metastatic seminoma. Its application can thus be recommended.
Keywords: FDG-PET, Seminoma, Testicular Cancer, Diagnosis, Residual Disease
1. Introduction
Testicular germ cell tumors, the most common malig-
nancies in young men, are classified as seminomas or
nonseminomas. Seminomas comprise about 50% of all
germ cell tumors, but their incidence has doubled in the
last 30 years [1]. More than 97% of patients with clinical
stage I disease can be cured by surgery and, if necessary,
adjuvant radiotherapy or carboplatin-based chemother-
apy. Approximately 25% are advanced-stage cases (Lu-
gano classification IIC or higher) requiring platinum-
containing polychemotherapy. The current guidelines of
the European Germ Cell Cancer Consensus Group (EG-
CCCG) now recommend combination chemotherapy with
cis-platinum, etoposide and bleomycin (PEB) [2,3]. Re-
sidual tumors are found in about 80% of patients with
systemic treatment; they can be diagnosed immediately
after chemotherapy [4,5].
The literature suggests that about 30% of residual le-
sions > 3 cm still contain vital tumor tissue; a biopsy or
resection followed by a histological workup was there-
fore advocated according to the recommendation of the
Sloan-Kettering Cancer Center [6,7]. However, resection
of these residual tumors by retroperitoneal lymphadenec-
tomy is associated with high morbidity, mainly due to
changes after chemotherapy [8,9]. Monitoring the lesions
by alternative diagnostic imaging techniques thus seems
a useful modality to avoid overtreating patients. How-
ever, size alone does not appear to be an optimal crite-
rion for identifying residual tumors or necrosis; sensitiv-
ity and specificity are limited when applying the speci-
fied 3 cm cut-off value [10,11]. The required imaging
technique should enable precise differentiation between
tumor tissue and necrosis. Since 2-18fluoro-2-deoxy-D-
glucose positron emission tomography (FDG- PET) is
suitable for localizing tissue areas of enhanced metabolic
activity, it has the potential for better detection of vital
tumors [12]. This is true for pure seminomas, but FDG-
PET is of limited value in detecting residual tumors of
nonseminomas, because it cannot differentiate mature
teratoma components from fibrosis or necrosis [13,14].
The fact that pure seminomas contain no teratoma com-
ponents could render this examination particularly valu-
able for detecting vital seminoma residuals.
In other malignant diseases, FDG-PET is already re-
garded as a valuable tool for diagnosing vital residual
tumors. High-quality data are available here particularly
for Hodgkin’s and non-Hodgkin’s lymphoma [15-18].
For seminomas, on the other hand, the available data
are sometimes not entirely consistent. The vast majority
of studies have demonstrated the usefulness of FDG-PET
in the follow-up of seminomas [19-22]. Only one study
reported no diagnostic gain: a study by Ganjoo et al. [23]
that dates back to 1999, a time when the FDT-PET tech-
nique was still in the early stages of development.
The present review study analyzes all current publica-
tions on this topic with the aim of determining whether
FDG-PET may provide a useful tool for assessing resid-
ual tumors of pure seminomas after chemotherapy and
whether it may offer an advantage over the solely size-
based CT assessment of residual tumors.
2. Materials and Methods
The electronic databases Pubmed and MEDLINE were
used to carry out a systematic literature search for origi-
nal studies on the value of FDG-PET for assessing re-
sidual tumors in the follow-up of patients with metastatic
seminoma after systemic therapy. The five studies pub-
lished on this topic thus far were examined, analyzed and
summarized with regard to relevant information (number
of patients, number of residual tumors examined, lesion
size, and FDG uptake). SPSS 17.0 software was used to
perform statistical calculations based on the data ob-
tained within the context of this meta-analysis.
3. Results
Our analysis included only four of the five studies pub-
lished on this topic, because two of them had overlap-
ping patient populations. In these studies, a total of 130
patients with residual tumors after chemotherapy for
high-stage seminomas were examined with regard to
FDG uptake by the lesions. The patients had a mean age
of 39.5 years.
Gonadal seminomas were initially diagnosed in 102
patients, while 20 had retroperitoneal and 8 mediastinal
primary tumors. All these patients had residual tumors
after primary first-line chemotherapy with a platinum-
based regimen. Moreover, the studies included 16 pa-
tients after relapse and salvage chemotherapy and an-
other 16 after high-dose chemotherapy and peripheral
stem cell transplantation (Table 1). The total number of
lesions examined and analyzed after systemic therapy
amounted to 161 because some of the patients had sev-
eral lesions and also because some of those in the studies
by Becherer et al. [19] and de Santis et al. [20] were
examined several times due to relapses and repeat FDG-
PET scans.
FDG-PET was used to examine all residual masses for
vital tumor tissue after systemic chemotherapy. The re-
sidual tumor status over time was determined by either
histological examination or clinical follow-up (mean
23.6 months) and imaging procedures. A total of 43 le-
sions (27%) were resected and submitted for histological
workup; 118 residual tumors (73%) were observed using
CT as a diagnostic aid.
Altogether, 33 of 161 residual tumors showed positive
FDG-PET findings (Table 2).
Of the 33 positive results, 23 were true-positive with a
sensitivity of 72% and a specificity of 92% (Table 3).
The diagnostic value of tumor size (maximum tumor
diameter > 3 cm or 3 cm) as the sole criterion was used
for comparison. It proved to be markedly less sensitive
and specific than the FDG-PET examination in its ability
to detect vital tumor tissue in residual masses (Table 3).
Moreover, only 20 of 71 tumors larger than three centi-
meters contained vital tumor tissue (positive predictive
value, PPV = 28%). Here tumor measurement alone had
a sensitivity of only 63%. On the other hand, vital semi-
nomas were detected in 12 of 86 tumors 3 cm (negative
predictive value, NPV = 86%).
In addition, the results of this meta-analysis clearly in-
dicate that, compared to the solely size-based assessment
of residual tumors, the use of FDG-PET can reduce the
probability of both over- and undertreatment. An evalua-
tion of the relatively small number of cases from the
various studies reviewed here suggests that the rate of
overtreated patients could be significantly reduced from
72% to 30% (p < 0.001; Fisher’s exact test) and that of
undertreated patients from 14% to 7% (p = 0.11; Table
4. Discussion
The management of residual tumors after chemotherapy
for seminoma is still controversially discussed. Retro-
spective analyses disclosed no advantage in additionally
irradiating the lesions after systemic therapy for metas-
tatic seminoma [24-26]. Thus there still remain the op-
tions of surgical excision or an “active surveillance”
strategy. There is general consensus that residual tumor
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Copyright © 2011 SciRes. OJU
Table 1. Overview of the patient population and residual tumors in the four publications comparing the two examination
Becheree et al. 2005 Hinz et al. 2008 Ganjoo et al. 1999 De Santis et al. 2001 TOTAL
Total patient population 48 20 29 33 130
Mean age 39 42 38 39 39.5
Primary testicular tumor 39 18 19 26 102
Primary retroperitoneal tumor 7 2 6 5 20
Primary mediastinal tumor 2 0 4 2 8
Total number of lesions 74 20 30 37 161
Status based on histology 13 20 1 9 43
Status based on follow-up 61 0 29 28 118
First-line chemotherapy 40 21 19 28 108
Second-line chemotherapy 7 1 3 5 16
High-dose chemotherapy 5 0 7 4 16
Table 2. Correlation of FDG-PET findings with measurements of the largest tumor diameter ( or > 3 cm) and with the real
presence of vital seminoma cells.
Becheree et al. 2005 Hinz et al. 2008 Ganjoo et al. 1999 De Santis et al. 2001 TOTAL
Residual tumor > 3 cm 27 12 18 14 71
Vital tumor (true positive) 11 1 1 7 20
No vital tumor (false positive) 16 11 17 7 51
Residual tumor 3 cm 47 8 8 23 86
No vital tumor (true negative) 43 6 4 21 74
Vital tumor (false negative) 4 2 4 2 12
Positive PET 12 12 1 8 33
True positive 12 3 0 8 23
False positive 0 9 1 0 10
Negative PET 62 8 29 29 128
True negative 59 8 23 28 119
False negative 3 0 5 1 9
Relapse 15 3 5 9 32
Table 3. Comparison of the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and the
theoretical over- or undertreatment associated with the solely size-based assessment of residual tumors vs. the FDG-PET
Specificity Sensitivity PPV NPV Overtreatment Undertreatment
Size or 3 cm 59.3% 62.5% 28.2% 86% 71.8% 14%
FDG-PET 92.2% 71.9% 69.7% 93% 30.3% 7%
size is associated with the probability of tumor relapse.
Residuals larger than three centimeters carry an ap-
proximately 30% risk of containing vital tumor tissue
[4,6,7,27]. However, surgical management of these le-
sions involves a high risk of postoperative morbidity
such as retrograde ejaculation and lymphatic or pancre-
atic fistulas [6]. On the other hand, a survival advantage
of operated seminoma patients was demonstrated by de
Santis et al. in 2004 [21], who compared analyses on
“active surveillance” vs. resection of residual tumors. In
fact, 6% (8 of 132) of the patients in the “active surveil-
lance” group died of the tumor disease or as a conse-
quence of salvage therapy, while no deaths (0 of 58) oc-
curred in the operated group [21].
FDG-PET is now a standard diagnostic technique for
detecting vital tumor tissue after chemotherapy, since it
identifies metabolically active areas in the examined
masses and thus enables easy and specific vital tumor
Five study groups have thus far investigated the use-
fulness of FDG-PET and have published partially con-
troversial results [19-23]. For this reason, it has not yet
been possible to recommend FDG-PET as a standard
procedure in the follow-up of seminoma patients. In the
meantime, however, the study group of Heidenreich et al.
[28] and the EGCCCG [2,3] generally recommend per-
forming retroperitoneal lymphadenectomy only after
obtaining positive PET results in patients with semino-
matous residual tumors after chemotherapy.
This study has re-evaluated and summarized the stud-
ies published thus far. The summary of all studies has
demonstrated that FDG-PET may be regarded as a highly
valuable tool for identifying true negative findings. The
negative predictive value was 93% and thus exceeded the
negative predictive value of the solely size-based tumor
assessment (3 cm, 86%). Avital residual tumors could
be detected with a specificity of 92% by FDG-PET and
only 59% by size determination. Residual tumors 3 cm
contained vital seminoma tissue in 14% of the cases;
regardless of tumor size, FDG-negative lesions showed
vital tumor tissue in only 7%. FDG-PET thus seems able
to better identify a group of patients who do not require
primary surgery for residual tumors after systemic ther-
apy. In patients with FDG-negative lesions, the increased
postoperative morbidity makes it seem justified to adopt
a watchful waiting attitude with observation of residual
tumors and to only consider resection if they grow larger.
However, false-positive findings in FDG-PET must
still be regarded as a problem. Comprising 30% of all
positive findings in FDG-PET, they would lead to over-
treatment of one third of all patients with FDG-PET-
positive residual tumors. At just under 70%, however,
the positive predictive value of the FDG-PET examina-
tion here was still significantly above that of using re-
sidual tumor size alone (28%) as the basis for making
treatment decisions. Nevertheless, a significant weak
point of the examination method is evident here [29].
In conclusion, an analysis of studies published thus far
indicates that FDG-PET may indeed be regarded as a
valuable diagnostic tool for examining postchemotherapy
tumor residuals in cases of pure seminoma. In particular,
it has proved superior to solely size-based tumor assess-
ment in its sensitivity and specificity as well as its posi-
tive and negative predictive value. Given that surgical
removal of residual tumors exceeding three centimeters
is widely recommended [20,21], overtreatment could be
reduced in more than half of all cases by relying on the
FDG-PET findings.
Considering the (false) positive findings in FDG-PET,
which include avital tissue in 30%, the decision to surgi-
cally remove the lesions should, in some cases, be partly
based on the tumor size and resectability and possibly
also the growth tendency and perioperative risk.
Moreover, the rate of false positive findings can be
further reduced by making sure that there is a time inter-
val of at least six weeks between the completion of che-
motherapy and the diagnostic FDG-PET scan. Perform-
ing the examinations too early increases the false posi-
tive rate. On the other hand, combined FDG-PET/CT
examinations are better able to morphologically assess
foci of increased FDG uptake, which optimizes the di-
agnostic value. In addition, PET examinations should be
assessed by an experienced nuclear medicine specialist;
if necessary, a second opinion should be sought at a spe-
cialized center. There are no data thus far on the use of
an alternative tracer, nor does it seem useful to repeat the
examination after a certain interval in view of the high
costs and low diagnostic gain.
5. Summary
In summary, the data presented here confirm that
2-18fluoro-2-deoxy-D-glucose positron emission tomo-
graphy corresponds to the current clinical standard in the
follow-up of residual tumors after systemic therapy for
advanced pure seminoma.
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