|Year : 2016 | Volume
| Issue : 2 | Page : 313-316
Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first-line chemotherapy from a tertiary cancer center in India
A Joshi1, S Zanwar1, N Shetty2, V Patil1, V Noronha1, G Bakshi1, G Prakash1, S Menon1, K Prabhash1
1 Tata Memorial Centre, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Father Muller Medical College Hospital, Mangalore, Karnataka, India
|Date of Web Publication||6-Jan-2017|
Tata Memorial Centre, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Unlike the developed countries, there is a lack of good epidemiologic data for testicular germ cell tumors (GCTs) in India with majority presenting in advanced stage. This study aims to elaborate on the epidemiology of testicular GCTs and response to standard first-line chemotherapy (CT). Methods: GCTs treated at our center from January 2013 to June 2014 were retrospectively analyzed. Patients underwent orchidectomy either outside or at our hospital. Based on stage and risk group, standard CT (bleomycin, etoposide, and cisplatin/etoposide and cisplatin/carboplatin AUC7) and radiotherapy were given as appropriate. Response was calculated based on the Response Evaluation Criteria in Solid Tumors. Statistical analysis was performed using SPSS 18 software. Results: Fifty nonseminomatous germ cell tumor (NSGCT) and 36 of SGCT cases were studied. 30%, 46%, and 64% of NSGCT and 11%, 28%, and 22% of SGCT had N2, N3, and M1 diseases, respectively. The mean nodal size was 7 cm (1.5–19) in NSGCT and 5.5 cm (1.3–11) in SGCT. As per the International Germ Cell Cancer Collaborative Group classification, in patients with metastatic disease, 9% of NSGCT were good, 53% were intermediate, and 38% were poor risk whereas 75% of SGCT were good and 25% were intermediate risk. Following CT among NSGCT, 5% and 71% had radiologic complete response (CR) and partial response (PR), respectively. Among SGCT, 46% and 38% had radiologic CR and PR, respectively. 22%, 53%, and 13% of NSGCT and 12%, 24%, and 20% of SGCT developed febrile neutropenia, Grade 3 or 4 hematological and nonhematological toxicities, respectively, after standard chemotherapy. Conclusions: GCTs in India present with high nodal and high-risk diseases wherein the standard first-line CT may not be adequate as curative therapy; however, significant chemotoxicity is also a hindrance.
Keywords: Chemotherapy outcomes, epidemiology in India, germ cell tumor
|How to cite this article:|
Joshi A, Zanwar S, Shetty N, Patil V, Noronha V, Bakshi G, Prakash G, Menon S, Prabhash K. Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first-line chemotherapy from a tertiary cancer center in India. Indian J Cancer 2016;53:313-6
|How to cite this URL:|
Joshi A, Zanwar S, Shetty N, Patil V, Noronha V, Bakshi G, Prakash G, Menon S, Prabhash K. Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first-line chemotherapy from a tertiary cancer center in India. Indian J Cancer [serial online] 2016 [cited 2020 Apr 2];53:313-6. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/313/197741
| » Introduction|| |
In developing countries, many germ cell tumor (GCT) patients present with advanced-stage and poor-risk disease with a high nodal disease burden. As a result, outcomes are likely to differ with standard first-line computed tomography (CT). Here, we present a retrospective analysis of GCTs treated at a tertiary cancer center in India between January 2013 and June 2014.
| » Methods|| |
GCTs treated at our center from January 2013 to June 2014 were retrospectively analyzed. Patients who had undergone orchidectomy outside were also included in this study. Detailed history and physical examination was done at presentation. At baseline, contrast-enhanced CT of the thorax, abdomen, and pelvis, ultrasound scrotum, and tumor markers (alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase) were done as staging workup. Magnetic resonance imaging of the brain and bone scan were done only in symptomatic patients. Complete blood counts, renal function tests, liver function tests, and pulmonary function test were done to look for organ function. Patients wishing for sperm banking were offered the same. Patients with testicular primary underwent a high inguinal orchidectomy. Patients who were not stable to undergo surgery were given upfront chemotherapy, and orchidectomy was done later. Those who had scrotal violation outside also underwent scrotal scar excision. Based on biopsy and tumor markers, they were staged and classified as having seminomatous (S) or nonseminomatous (NS) GCTs. Histological classification was done according to the WHO, and staging was done according to the 2009 TNM of the International Union Against Cancer. For patients with metastatic disease, risk stratification was done according to the International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification system. Chemotherapy and radiotherapy were given as per the standard guidelines based on stage and risk. Response was calculated based on the Response Evaluation Criteria in Solid Tumors (RECIST). Statistical analysis was performed using SPSS 18 software (SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago).
| » Results|| |
Fifty of nonseminomatous germ cell tumor (NSGCT) and 36 of SGCT cases were studied. The mean age was 28 years (17–70) for NSGCT and 39 years (22–65) for SGCT. Six percent of NSGCT and 14% of SGCT had cryptorchidism. 30%, 46%, and 64% of NSGCT and 11%, 28%, and 22% of SGCT had N2, N3, and M1 diseases, respectively. The mean nodal size was 7 cm (1.5–19) in NSGCT and 5.5 cm (1.3–11) in SGCT. Twenty-two percent of NSGCT and 17% of SGCT had scrotal violation outside. As per the IGCCCG classification, in patients with metastatic disease, 9% of NSGCT were good, 53% were intermediate, and 38% were poor risk whereas 75% of SGCT were good and 25% were intermediate risk. Following CT among NSGCT, 5% and 71% had radiologic complete response (CR) and partial response (PR), respectively, and 40% of NSGCTs underwent retroperitoneal lymph node dissection (RPLND) and in 6% RPLND could not be done due to extensive lymph nodal disease. Among SGCT, 46% and 38% had radiologic CR and PR, respectively. Nearly 22%, 53%, and 13% of NSGCT and 12%, 24%, and 20% of SGCT developed febrile neutropenia (FN), Grade 3 or 4 hematological and nonhematological toxicities, respectively, after standard chemotherapy. In NSGCT, none of the cases with N3 disease achieved CR, while in SGCT, three patients (30% of N3) achieved CR. Nineteen percent of NSGCT patients did not achieve tumor marker negativity post first-line chemotherapy. After RPLND, 20% of NSGCT cases had a residual viable tumor in histopathology specimen. Baseline characteristics are shown in [Table 1], and treatment details are shown in [Table 2].
| » Discussion|| |
With the exceptions of few small series, there is a lack of recent data from India on GCT epidemiology, the response rates, and toxicity profile of first-line chemotherapy.
In our study, 58% of NSGCTs belonged to poor- or intermediate-risk group, with 46% of NSGCT having N3 24 disease and 64% having metastatic disease at presentation. This figure is substantially higher than that reported from developed countries where the combined poor- and intermediate-risk NSGCTs account for 20–30% cases and that of N3 disease account for only 10–15%. Similarly, 28% of SGCTs in our study had N3 nodal disease, a number substantially higher than that reported from the west where it is fewer than 5%. Although these high percentages can be attributed to a referral bias and delay in presentation to a tertiary care center, this is likely to be the case across the country as most of these malignancies are being managed at tertiary care centers only due to a lack of enough infrastructure and trained personnel at the primary and secondary care centers. Furthermore, almost 22% of NSGCTs and 17% of SGCTs had scrotal violation at the time of orchidectomy. All these were performed at peripheral centers before these patients were referred to our institute again highlighting the ignorance of orchidectomy procedure for GCT at the peripheral centers in India. The significance of this finding on the long-term outcomes is unclear as all of them underwent scrotal scar excision postchemotherapy, and in addition, there was a substantial nodal disease burden postchemotherapy thereby obviating the impact of scrotal violation. After first-line chemotherapy, only 5% of NSGCTs had radiologic CR as per RECIST. These results were disappointingly low. In previous studies, even in poor-risk subset, four cycles of bleomycin, etoposide, and cisplatin (BEP) resulted in achievement of CR in 55–88% cases.,, The major challenge in treating NSGCT at our center has been the presence of bulky nodal disease reflected in the fact that none of the cases with N3 nodal NSGCT achieved a CR. Forty percent of NSGCT underwent retroperitoneal lymph node dissection (RPLND) and 6% were unamenable to surgical resection post first-line chemotherapy. After RPLND, 20% of cases had a residual viable tumor in histopathology specimen which again is a poor prognostic marker.,,
In SGCTs, which had predominantly good-risk disease, CR rates were only 17%. This again is much lower than previous reports of good-risk disease of SGCTs where the CR rates with first-line chemotherapy were in the range of 88–97%. Six percent of cases underwent RPLND and 6% were unamenable for surgical resection.
Among patients who received first-line chemotherapy with BEP or etoposide and cisplatin at our institute, FN occurred in 20% cases and Grade 3/4 hematologic toxicity was present in 42% cases, which is close to previously reported literature., Grade 3/4 nonhematologic toxicity was present in 18% cases. Granulocyte colony-stimulating factor (G-CSF) use was required in 51% of NSGCTs and 48% of SGCT to maintain the adequate dose intensity. Dose reduction was required in 13% of NSGCT and 12% of SGCT. The primary G-CSF prophylaxis was not used in any of these cases. Bleomycin-induced lung injury was reported in 11% of NSGCT and 8% of SGCT. This percentage is in unison with previous reports.
There is an unmet need of a better chemotherapy regimen than the standard BEP for GCTs in first-line setting with high nodal disease burden. The factors which we believe were the major hurdles in achieving optimal outcomes were a high nodal disease, especially in NSGCT, poor dose intensity, and dose reductions due to poor tolerance of chemotherapy and a high rate of treatment default. Thirteen percent of cases defaulted for further therapy after first-line chemotherapy. The most common reasons for default were logistic constraints to stay away from home for the further therapy, financial constraints, and unwillingness for surgery due to the expected complications.
This study also highlights that early presentation and referral to a cancer center and proper implementation of orchidectomy technique by general practitioners at the peripheral centers may go a long way in improving the outcomes of GCT in our country. Use of an alternative chemotherapy regimen to improve outcomes for patients with high nodal disease burden can also be further explored.
The major caveat of our study was its retrospective nature and lack of reporting of the median average dose intensity.
| » Conclusions|| |
GCTs in India present with high nodal and high-risk diseases wherein the standard first-line CT may not be adequate 18 as curative therapy; however, significant chemotherapy related oxicity is also a hindrance.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Eble JN, Sauter G, Epstein JI, Sesterhenn IA, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press; 2004.
Sobin LH, Gospodarowicz MK, Wittekind Ch; International Union against Cancer. TNM classification of malignant tumours. 7th
ed. 2009. Chichester, West Sussex, UK; Hoboken, NJ: Wiley-Blackwell; 2010.
International germ cell consensus classification: A prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997;15:594-603.
Bhutani M, Kumar L, Seth A, Thulkar S, Vijayaraghavan M, Kochupillai V. Germ cell tumours of the testis: Clinical features, treatment outcome and prognostic factors. Natl Med J India 2002;15:18-21.
van Dijk MR, Steyerberg EW, Habbema JD. Survival of non-seminomatous germ cell cancer patients according to the IGCC classification: An update based on meta-analysis. Eur J Cancer 2006;42:820-6.
Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987;316:1435-40.
de Wit R, Stoter G, Sleijfer DT, Kaye SB, de Mulder PH, ten Bokkel Huinink WW, et al.
Four cycles of BEP versus an alternating regime of PVB and BEP in patients with poor-prognosis metastatic testicular non-seminoma; a randomised study of the EORTC Genitourinary Tract Cancer Cooperative Group. Br J Cancer 1995;71:1311-4.
Kaye SB, Mead GM, Fossa S, Cullen M, deWit R, Bodrogi I, et al.
Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: A Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study. J Clin Oncol 1998;16:692-701.
Gerl A, Clemm C, Schmeller N, Dienemann H, Lamerz R, Kriegmair M, et al.
Outcome analysis after post-chemotherapy surgery in patients with non-seminomatous germ cell tumours. Ann Oncol 1995;6:483-8.
Stenning SP, Parkinson MC, Fisher C, Mead GM, Cook PA, Fossa SD, et al.
Postchemotherapy residual masses in germ cell tumor patients: Content, clinical features, and prognosis. Medical Research Council Testicular Tumour Working Party. Cancer 1998;83:1409-19.
Spiess PE, Brown GA, Pisters LL, Liu P, Tu SM, Evans JG, et al.
Viable malignant germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection specimen: Can it be predicted using clinical parameters? Cancer 2006;107:1503-10.
de Wit R, Roberts JT, Wilkinson PM, de Mulder PH, Mead GM, Fosså SD, et al.
Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: A randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 2001;19:1629-40.
Daugaard G, Nielsen H, Bruun B, Hansen F, Geertsen P, Schønheyder H. Infections in patients treated with high-dose chemotherapy for germ cell tumours. Eur J Cancer 1993;29A: 2220-2.
O'Sullivan JM, Huddart RA, Norman AR, Nicholls J, Dearnaley DP, Horwich A. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol 2003;14:91-6.
[Table 1], [Table 2]