winter_Layout 1 16/03/2010 10:35 Page 23
Optimising Treatment of Testicular Cancer
Non-seminoma stage IIA/B without elevated tumour markers can be six weeks after chemotherapy. The need for an RTR in the face of
treated with primary RPLND, if possible using a nerve-sparing normal CT findings is controversial. CT criteria alone are not
technique. If undifferentiated embryonal carcinoma is detected, sufficiently reliable to distinguish viable tumour or teratoma from
adjuvant chemotherapy with two cycles of BEP is indicated, necrosis. Overall, following chemotherapy, only 10% of residual
depending on the size of metastatic disease and lymph-node density. masses contain viable cancer, 50% contain mature teratoma and
If teratoma is detected, post-operative surveillance is recommended 40% contain necrotic tissue. Unresected teratoma or viable GCT are
after a complete resection. As an alternative to RPLND, a surveillance at least partly chemorefractory and, if untreated, will progress. So,
strategy with a follow-up examination at six weeks is indicated to completeness of resection is an independent and consistent
evaluate whether the retroperitoneal lesion has grown, is stable or predictive variable of clinical outcome.
has shrunk. In cases where progressive or stable disease with
negative tumour markers, a teratoma or a growing undifferentiated In RTR, surgical margins should not be compromised in an attempt to
malignant tumour is suspected, RPLND is indicated. A shrinking lesion preserve ejaculation, although nerve-sparing dissections are
is likely to be of non-malignant origin and should be observed in possible in patients with marker normalisation after chemotherapy
further follow-up examinations. and necrotic tissue in frozen-section histology. In these patients,
nerve-sparing techniques and the reduction of the surgical field to
Treatment of Advanced Seminoma/ the left- or right-sided template are applicable to preserve antegrade
Non-seminoma Stages IIC and III ejaculation and fertility.
In advanced GCT, chemotherapy with BEP, etoposide plus cisplatin or PEI
(cisplatin, etoposide, ifosfamide) according to IGCCCG risk classification The size and location of residual masses make RTR a technically
remains standard treatment. In ‘good-prognosis’ patients, three cycles demanding procedure that should be performed by experienced
of BEP or (in cases of bleomycin contraindications) four cycles of surgeons in dedicated referral centres. Flechon et al. at the 2004
etoposide plus cisplatin should be given. In ‘intermediate/poor- meeeting of the American Society of Clinical Oncology (ASCO)
prognosis’ patients, four cycles BEP or four cycles of PEI are published a retrospective analysis comparing number of procedures
recommended. In several phase III trials, other chemotherapy regimens and adherence to guideline recommendations with clinical outcome.
have not proved to be more effective or less toxic. For example, recently They investigated the impact of conformity in RTR surgical
Culine et al. compared CISCA/VB (cyclophosphamide, doxorubicin, procedures and the experience level of the surgeon. RTRs were
cisplatin/vinblastine, bleomycin) versus the four-cycle BEP standard performed in 153 patients after chemotherapy by 67 different
regimen in advanced non-seminoma patients with ‘intermediate/poor surgeons. One experienced surgeon operated on 49 patients and the
prognosis’. They showed equivalent efficacy but higher haematological remaining 104 patients were operated on by 66 different surgeons.
and gastrointestinal toxicity in the CISCA/VB-treated group compared All of the latter operated fewer than eight times within the eight-year
with the BEP group, suggesting that the standard treatment should period studied. In 71 of 153 evaluated patients, RTR was performed
remain four cycles of BEP.
25
according to standard recommendations. Conformity was 100% for
the experienced surgeon who operated on 49 patients in a referral
Re-staging examination has to be performed by imaging or centre and 26% for the other 66 surgeons. In a median follow-up time
re-evaluation of tumour markers after two cycles of chemotherapy. In of three years they observed 26 (17%) relapses (12 in the
cases of adequate tumour marker decline and stable or regressive retroperitoneum) and 14 deaths. Patients who had received non-
tumour manifestation, the initiated chemotherapy should be conforming RTR had a 4.33 relative risk of retroperitoneal relapse and
completed. If tumour markers decline but metastases grow, a a 3.17 relative risk of death, respectively, compared with patients
presence of ‘growing teratoma syndrome’ is possible and resection of who had RTR performed according to standard recommendations.
the tumour is obligatory, at least directly after completion of They concluded that completeness of tumour resection is a
chemotherapy in cases of positive markers. In ‘poor-prognosis’ predictive variable of clinical outcome and that RTR should be
patients with a slow, inadequate tumour marker decline after the first performed in the recommended modality and by experienced
cycles of chemotherapy dose intensification, a different regimen or surgeons in referral centres.
27
high-dose chemotherapy should be discussed.
After residual tumour resection with detection of necrosis or mature
Treatment of Residual Lesions teratoma with complete resection, no further treatment is required.
After completing chemotherapy or radiotherapy, an evaluation of In the case of incomplete resection of vital carcinoma or immature
tumour markers and imaging investigations is mandatory. A residual teratoma or detection of more than 10% of viable tumour in the
mass of seminoma should not be resected, irrespective of size, but resected specimen, consolidation chemotherapy (two cycles of PEI)
rather monitored by imaging investigations and tumour markers. FDG- may be justified, according to an analysis by Fizazi et al.
28
PET has a high positive and negative predictive value regarding the
question of remaining vital disease in patients with residual masses Treatment of Relapsed or Refractory
after treatment of seminoma.
26
In patients with positive FDG-PET, a Germ Cell Tumours
biopsy or resection has to be obtained. Based on histopathological In patients who relapse or suffer from a refractory disease, the
results, further treatment (surveillance, residual tumour resection, standard treatment after first-line chemotherapy consists of salvage
radiotherapy or chemotherapy) has to be discussed. If markers (LDH, chemotherapy of four cycles of PEI/VIP, four courses of TIP
β-HCG) are positive, salvage chemotherapy is indicated. (paclitaxel, ifosfamide plus cisplatin) or three cycles of VeIP
(vinblastine, ifosfamide plus cisplatin). The option of high-dose
RTR is necessary when residual radiographic abnormalities are chemotherapy still represents a curative option for patients with
present after chemotherapy, and should be performed within four to second or subsequent relapses. A salvage residual tumour resection
EUROPEAN UROLOGICAL REVIEW 23
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100