949 EXTREMELY LOW RECURRENCE RATE AFTER LONG EXPERIENCE WITH ADJUVANT CARBOPLATIN MONOTHERAPY FOR CLINICAL STAGE I SEMINOMA

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Extremely low recurrence rate after long experience with adjuvant carboplatin monotherapy for clinical stage I seminoma

Long-term impaired language and decreased wellbeing among testicular cancer survivors who received chemotherapy – results from Swenoteca

Steiner H.1, Scheiber K.2, Zangerl F.1, Stoehr B.1, Fritzer A.1, Leonhartsberger N.1

Skoogh J.1, Steineck G.2, Stierner U.3, Cavallin-Ståhl E.4, Olofsson U.2, Wallin A.5, Gatz M.6, Johansson B.7, on behalf of Swedish-Norwegian Testicular Cancer Group (SWENOTECA)

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Medical University Innsbruck, Dept. of Urology, Innsbruck, Bezirkskrankenhaus Hall In Tirol, Dept. of Urology, Hall In Tirol, Austria

Austria,

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Introduction & Objectives: Radiotherapy has been the standard treatment of patients with clinical stage I seminoma for decades. Carboplatin has been advocated as an effective treatment alternative to avoid well known late effects of radiotherapy (including second malignancy and gastrointestinal toxicity) and the high recurrence rate of surveillance. Since carboplatin monotherapy was initiated more than 18 years ago, we evaluate the long term oncological effectiveness and morbidity. Material & Methods: From February 1990 until August 2008, 226 patients received two adjuvant cycles of single-agent carboplatin (400mg/m² body surface, day 1 and day 22) two weeks after high inguinal orchiectomy. Patients were followed for a long period of time to asses for oncologic efficacy and side effects. Results: Most important, during mean follow up of 64 months (range 2-227) only two patients (0.8%) developed recurrent para-aortic tumour within the first year, both patients received cisplatin-based chemotherapy as successful salvage therapy. 5 (2.2%) patients developed a contralateral tumour (after 24, 25, 55, 120 and127 months). In all patients carboplatin was well tolerated associated with only mild gastrointestinal complaints. No patient developed neutropenic fever. Thrombocytopenia was observed in 27.0% patients with thrombocyte levels below 20x109/L in 1.0% patients after the second treatment cycle. Carboplatin was not associated with neurotoxicity, ototoxicity or nephrotoxicity. 48 patients were followed elsewhere after a mean follow-up of 45 months. 2 patients died of other causes, no patient died of testicular cancer. Currently, all patients still in follow-up are alive with no evidence of disease. Conclusions: Long term results confirm early reports - in stage I seminoma two cycles of carboplatin monotherapy were found highly effective from an oncologic standpoint and associated with only minimal morbidity.



Sahlgrenska Academy, Dept. of Clinical Cancer Epidemiology, Dept. of Psychology, Gothenburg, Sweden, 2Sahlgrenska Academy, Dept. of Clinical Cancer Epidemiology, Gothenburg, Sweden, Sahlgrenska University Hospital, Dept. of Oncology, Gothenburg, Sweden, 4Lund University Hospital, Dept. of Oncology, Lund, Sweden, 5Sahlgrenska Academy, Institute of Neuroscience and Physiology, Gothenburg, Sweden, 6University of Southern California, Dept. of Psychology, Los Angeles, United States of America, 7Sahlgrenska University Hospital, Dept. of Psychology, Gothenburg, Sweden 1

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Established prognostic models fail to predict the outcome of dose dense chemotherapy for the treatment of recurrent germ cell tumours (GCTs) Gerlinger M., Wilson P., Powles T., Oliver R.T.D., Shamash J. St. Bartholomew’s Hospital, Dept. of Medical Oncology, London, United Kingdom Introduction & Objectives: Prognostic models are used to predict the outcome of patients with relapsed GCTs. The results of these models are inconsistent. This may in part be due to treatment factors rather than patient factors as a spectrum of different treatment regimens were used in these models. Our institution uses dose dense cisplatin regimens and therefore we investigated the validity of established prognostic models and individual prognostic factors with these regimens. Material & Methods: A prospective database of 117 consecutive patients at first recurrence of GCTs was analysed. Sixty-six of these patients were treated with weekly MBOP chemotherapy between 1986 and 1997 (MBOP era), while 51 received weekly GAMEC chemotherapy between 1998 and 2008 (GAMEC era). The established prognostic systems in this setting (Fosså, Br J Cancer 1999:80 1392- and Motzer, Cancer 1991:67 1305-, subsequently modified by Kondagunta) were applied to patients from both eras independently, in an attempt to validate them. Furthermore we used multivariate analysis to identify other potential markers in this setting.

Introduction & Objectives: To study cognitive function among testicular cancer patients who received chemotherapy compared to those who received no chemotherapy. Material & Methods: Since 1981 Swedish clinicians have prospectively reported clinical data to the SWENOTECA database so far including four treatment protocols. In this database we identified 1224 men diagnosed between January 1981 and December 2004 being between 18 and 75 years old January 15, 2007 and with a residential address available in the Swedish population-based register of all citizens. We excluded those who had had brain metastases (n=12), died before (n=1) introduction letter was sent, with an ongoing cancer disease (n=2), who did not understand Swedish (n=5) or lived abroad (n=6), leaving 1198 eligible men. During an 18-month qualitative phase, we interviewed 40 subjects, formulated questions based on this information and made a study-specific questionnaire on cognitive functions. We also formulated questions about well-being. Preliminary versions were tested for validity face to face, revised and finally used in a preparatory study. The procedures followed the established routines at a format developed at our division (Clinical Cancer Epidemiology). Results: We obtained information from 978/1198 (82%) testicular cancer survivors 3 to 26 years after the diagnosis. We found significantly poorer results on 5 of 7 analysed language questions for those who received 5 or more cycles of chemotherapy compared with those who received no chemotherapy. Prevalence of “producing similar but incorrect words“ at least once a week was 5 percent among those having received no chemotherapy versus 16 percent among those who received 5 or more cycles, giving a prevalence ratio (“relative risk”, RR) of 3.3 with a 95 percent confidence interval of 1.5-7.2. Corresponding figures for “saying words in the wrong order” was 3.1 (1.7-5.9), “difficulties understanding what other people mean” 3.2 (1.3-7.8), “saying other words than planned” 2.3 (1.14.6) and for “problems completing your sentences” 2.2 (1.0-3.7). Prevalence of a “little, moderately or much” affected well-being due to difficulties “finding words and other language difficulties” was 17 percent among those having received no chemotherapy versus 36 percent among those having received 5 or more cycles, giving a prevalence ratio (“relative risk”, RR) of 2.0 with a 95 percent confidence interval of 1.3-3.0. Corresponding figures for “slow thinking speed” was 1.7 (1.1-2.8), “memory” 1.7 (1.1-2.6) and “concentration” 1.6 (1.1-2.3). Conclusions: Testicular cancer patients who received 5 or more cycles of cisplatin-based chemotherapy are at risk of developing cognitive long-term side-effects which can affect well-being.



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Teratoma with malignant transformation in adult male germ-cell cancer: A large retrospective review at fondazione IRCCS Istituto Nazionale dei Tumori (INT) of Milan Necchi A.1, Colecchia M.2, Nicolai N.3, Carbone A.2, Piva L.3, Biasoni D.3, Torelli T.3, Stagni S.3, Milani A.3, Salvioni R.3 Fondazione Irccs Istituto Nazionale Dei Tumori, Dept. of Medical Oncology, Milan, Italy, 2Fondazione Irccs Istituto Nazionale Dei Tumori, Dept. of Pathology, Milan, Italy, Fondazione Irccs Istituto Nazionale Dei Tumori, Dept. of Genitourinary Oncology, Milan, Italy

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Introduction & Objectives: Teratoma with malignant transformation (TMT) is a rare phenomenon characterized by a somatic differentiation within a germ-cell tumor. Little is known concerning clinical implications about malignant transformation. We present our last 25-years experience of 28 cases. Material & Methods: Patients (pts) with a malignant transformation (MT) within germ-cell tumor have been retrospectively identified from surgical pathology files at INT Milan from 1981 to 2007 and clinical as well as pathological data have been collected. All slides were reviewed and immunohistochemistry performed.

Results: Patients characteristics and outcome were similar in both eras apart from a lower median age and the more frequent use of first line chemotherapy that is nowadays considered to be sub-standard in the MBOP era (p<.05). In the MBOP era the model by Fosså successfully identifies two distinct groups in terms of PFS (2y PFS: good:68% poor:28%, p=.004) but this does not hold when OS is considered (p=.09). This model also fails in the GAMEC era when good and poor prognostic groups have similar PFS and OS. The modified Motzer criteria failed to identify statistically significant differences in the good and poor prognosis groups for both PFS and OS in the MBOP era (2y PFS: good: 69% poor: 48%; 2y OS: good: 79% poor: 61%) and the GAMEC era (2y PFS: good: 69% poor: 40%; 2y OS: good: 93% poor: 62%) (p>.05 for each). Multivariate analysis showed a raised LDH is the only significant predictor of poor OS (p=.001) and PFS (p=.05) in the MBOP era. In the GAMEC era, LDH predicts for poor PFS (p=.002) but not OS. Age above 35 years is a further independent predictor of poor PFS in the GAMEC era (p=.002).

Results: A total number of 28 pts was recorded, 10 pts had MT in the primary only, 2 both in primary and in metastatic sites and 16 in metastatic sites only. Out of 12 pts with MT in the primary, 9 had been treated with primary retroperitoneal lymph-node dissection (RPLND) followed by surveillance only in 7 patients with no retroperitoneal metastases and by adjuvant chemotherapy in 2 patients who had resection of nodal disease: all of them remained disease-free at a median follow-up of 20 years (range: 51-324+ months); 3 pts received primary chemotherapy followed by surgery and 2 of them remained disease-free at 6+ and 285+ months. 14 of 16 patients who had MT following induction chemotherapy for advanced disease are evaluable: 6 had a radical removal of disease and 5 of them remained diseasefree at 75 months of median follow-up (4-79+). Out of 8 who had not a radical removal of residual disease, 3 can be rescued by further chemotherapy and are disease free at 35+, 39+ and 77+ months of follow-up. So far, all 7 patients with no metastases remained alive and disease-free, as well as 7 of 8 patients who had a radical surgery of metastatic sites in their history, versus only 5 of 11 patients who could not receive a radical excision of disease.

Conclusions: This work demonstrates that the Fosså and modified Motzer prognostic systems are not consistently applicable to patients treated with dose dense chemotherapy. It appears that other factors such as age and LDH may be more useful, and underlines the fact that treatment regimens may be a significant factor in this setting. This is relevant for the ongoing international effort to define prognostic factors for recurrent GCTs.

Conclusions: This is one of the largest series of MT of germ-cell tumors. All patients with no metastatic sites are alive and disease free (7/7). Among patients with advanced disease those who were submitted to a radical excision of metastases prior to or following chemotherapy had better outcome (7/8). Nonetheless, rescue chemotherapy was able to cure nearly half (5/11) of not radically respectable patients.

Eur Urol Suppl 2009;8(4):358