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Management of testicular cancers

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Management of testicular cancers

Management of testicular cancers

  1. 1. Management of Testicular Tumors Dr. Mohd Waseem Raza Moderator- Dr. Subhash Gupta
  2. 2. Introduction • 1-2 % of all male malignancies. • Most common malignancy in young adult males (aged 15-40 years) • 2 to 3% Testicular Tumour are bilateral • Worldwide Incidence is 1.5/lakh (Globocan 2008) • Incidence in India 0.5/lakh (Globocan 2008)
  3. 3. Lymphatic Drainage • Right testis: along the IVC inter-aortocaval region  pre-aortic & para-aortic lymph nodes, with possible cross-over within the retroperitoneum • Left testis: Preaortic and para-aortic lymph nodes around the left renal hilum  inter-aortocaval nodes mostly without cross-over • Retroperitoneal lymph nodes are located anterior to the T11 to L4 vertebral bodies concentrated at the L1–L3 level • Nodal spread to ipsilateral iliac chain is ~3% • Scrotal skin: lymphatics drain into the inguinal and external iliac nodes.
  4. 4. Aetiology of testicular tumour • • Cryptorchidism - 5-fold increase in incidence. Eutopic (descended) testis-10% (Pottern et al. J Natl Cancer Inst. 1985;74:377-381; Swerdlow AJ, Higgins CD, Pike MC. Risk of testicular cancer in cohort of boys with cryptorchidism. BMJ. 1997;314:1507-1511) • Family history - increases the likelihood of developing testicular GCT. [Dieckmann 1997; Chia 2009; Lutke Holzik 2004; Polednak 1996;Westergaard 1996]
  5. 5. • Risk of developing a new contralateral primary tumor - 2% [Fossa 2005] • Subfertility , infertility, and testicular feminization. [Richiardi 2004; Raman 2005; Møller 1999; Jacobsen 2000; Guazzieri 1985] • Marijuana use -- 2 fold increased incidence of NSGCT [Daling 2009; Trabert 2011] • • • Altered intrauterine hormonal environment Immunosuppression Mediastinal GCTs : more common in Klinefelter’s syndrome patients .
  6. 6. Histologies of Testicular Neoplasms
  7. 7. Testicular Tumour & Molecular Biology Proto-oncogenes in Germ Cell Tumours Seminoma & Embryonal Carcinoma Seminoma N-myc expression Immature Teratomas c-erb B-1 and c-erb b-2 expression c-Ki-ras expression (Shuin T et al. Differential expression of protooncogenes in human germ cell tumors of the testis. Cancer 1994 Mar 15;73(6):1721-7)
  8. 8. Molecular Biology cont.. GCT consistent with: • Gain Chromosome No. • Loss 11, 13 and 18 7, 8 and X Most consistent structural chromosomal abnormality is an isochromosome 12p. Spermatocytic seminomas-- Gain of chromosome 9 Looijenga LH et al. Pathogenesis of testicular germ cell tumours. Reviews of Reproduction (1999) 4, 90–100
  9. 9. Diagnostic and Staging work up • Pre-requisites are: a) History b) Clinical Examination c) Radiological procedure - USG / CT ± MRI ± Bone Scan d) Tumour Markers - β HCG, AFP, LDH e) Pathology of Tumour Specimen
  10. 10. Clinical Features • Painless Swelling of One Gonad • Dull Ache or Heaviness in Lower Abdomen • Acute Scrotal Pain-10% • Present with Metatstasis -10% - Neck Mass / Cough / Anorexia / Vomiting / Back Ache/ Lower limb swelling • Gynecomastia- 5% • Rarely - Infertility Dictum For Any Solid Scrotal Swellings: All patients with a solid, Firm Intratesticular Mass that cannot be Transilluminated should be regarded as Malignant unless otherwise proved
  11. 11.  ultrasound – B/L testis- confirms a solid testicular mass.  CT scans of the abdomen and pelvis with chest imaging by either CT or standard x-ray. • Lymph nodes measuring > 5 mm in a landing zone are suspicious for metastatic disease in a patient with a known testicular tumor.  MRI: • If iodinated contrast dye is contraindicated • Useful for defining vascular anatomy before surgical management of bulky retroperitoneal masses
  12. 12.  Bone scan and brain imaging (CT or MRI) are not part of routine staging.  Positron emission tomography (PET) -not useful in routine staging. • Neither small lesions nor teratoma can be identified by PET (false negative) and inflammatory processes such as sarcoidosis often demonstrate fluorodeoxyglucose avidity (false positive). (de Wit M, Brenner W, Hartmann M, et al. Ann Oncol. 2008;19:1619-1623; Oechsle K, Hartmann M, Brenner W, et al. J Clin Oncol. 2008;26:5930-5935)
  13. 13. Tumour Markers 1.Onco-fetal Substances 2.Cellular Enzymes AFP – HCG – ( Alfafetoprotein ) ( Human Chorionic Gonadotropin ) 1. LDH (Lactate dehydrogenase) Normal:<16 ngm / Has α and β polypeptide chain ml Half Life: 5 to 7 d Normal: < 1 ng / ml Half Life: 24 to 36 hours Raised AFP : Raised β HCG Pure embryonal ca 100 % - Choriocarcinoma Teratocarcinoma 60% - Embryonal ca Yolk sac Tumour 55% - Teratocarcinoma Combined Tumour 25% - Yolk Cell Tumour 7% - Seminomas N=105 - 333 IU/L metastatic seminoma- 80% and metastatic nonseminoma-60% of patients 2.PLAP Elevated -50% of seminomas at presentation (half-life of 24 hours). AFP Not raised is Pure Choriocarcinoma or Pure Seminoma
  14. 14. Role of Tumour Markers • Helps in Diagnosis - 80 to 85% of Testicular Tumours have Positive Markers • Indicates histology of Tumour • Tumour Burden • Residual • Response Evaluation
  15. 15. Royal Marsden staging system STAGE I Limited to testis IIA Nodes <2 cm IIB Nodes 2–5 cm IIC Nodes 5–10 cm IID Nodes >10 cm III Nodes above and below diaphragm IV Extralymphatic mets
  16. 16. AJCC 7th Edition pTX Primary tumor cannot be assessed. pT0 No evidence of primary tumor (e.g., histologic scar in testis). pTis Intratubular germ cell neoplasia (carcinoma in situ). pT1 Tumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis. pT2 Tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis. pT3 Tumor invades the spermatic cord with or without vascular/lymphatic invasion. pT4 Tumor invades the scrotum with or without vascular/lymphatic invasion. NX Regional lymph nodes cannot be assessed. N0 No regional lymph node metastasis. N1 Metastasis with a lymph node mass ≤2 cm ; or multiple lymph nodes, none >2 cm in greatest dimension. N2 Metastasis with a lymph node mass >2 cm but not >5 cm ; or multiple lymph nodes, any one mass >2 cm but not >5 cm in greatest dimension. N3 Metastasis with a lymph node mass >5 cm in greatest dimension.
  17. 17. M0 No distant metastasis. M1 Distant metastasis. M1a Nonregional nodal or pulmonary metastasis. M1b Distant metastasis other than to nonregional lymph nodes and lung. Serum Tumor Markers (S) Required for Staging SX Marker studies not available or not performed. S0 Marker study levels within normal limits. S1 LDH <1.5 × N and hCG (mIu/ml) <5,000 and AFP (ng/ml) <1,000. S2 LDH 1.5–10 × N or hCG (mIu/ml) 5,000–50,000 or AFP (ng/ml) 1,000–10,000. S3 LDH >10 × N or hCG (mIu/ml) >50,000 or AFP (ng/ml) >10,000. N indicates the upper limit of normal for the LDH assay.
  18. 18. STAGE GROUPING III B
  19. 19. IGCCCG Prognostic System for Advanced-Stage GCT Risk Group Pts, % Criteria 5-Yr DFS, % 5-Yr OS, % 89 92 Intermediate 28 risk Requires gonadal or retroperitoneal 75 primary tumor, absence of NPVM, and ≥ 1 of the following: HCG 5000-50,000 mIU/dL, AFP 1000-10,000 ng/dL, or LDH 1.5-10.0 x ULN 80 Poor Risk Requires any of the following: mediastinal 41 primary tumor site, presence of NPVM, HCG > 50,000 mIU/dL, AFP > 10,000 ng/dL, or LDH > 10 x ULN 48 Nonseminoma Good risk 56 16 Requires all of the following: gonadal or retroperitoneal primary tumor, absence of NPVM, HCG < 5000 mIU/dL, AFP < 1000 ng/dL, and LDH < 1.5 x ULN
  20. 20. IGCCCG Prognostic System for Advanced-Stage GCT cont.. Risk Group Pts, % Criteria 5-Yr DFS, % 5-Yr OS, % Seminoma Good risk 90 Absence of NPVM 82 86 Intermediate 10 risk Presence of NPVM 67 72 International Germ Cell Consensus Classification Group: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol. 1997;15:594-603.
  21. 21. MANAGEMENT Sperm banking must be discussed with the patients before undergoing any therapeutic intervention that may compromise fertility including RT ,Surgery and CT. Management of testicular tumor is combined modality treatment. Various treatment modalities are: •Surgery •Surveillance •Radiotherapy •Chemotherapy
  22. 22. Surgery Radical orchidectomy: • All patients • done via an inguinal incision, with cross clamping of spermatic cord vasculature and delivery of testis into the surgical field. • Scrotal violation, increased local/regional recurrence, but no difference in distant recurrence rate or overall survival.
  23. 23. Stage wise management of seminoma Stage I • Surgery surveillance radiotherapy chemotherapy
  24. 24. Surveillance • Indication: Pts. who can comply. • Sites for relapses – Retroperitoneum- 76-94% – Mediastinum- 5-15% – Inguinal-3-11%
  25. 25. Whether All Stage I patients should be considered for surveillance?
  26. 26. Prognostic Factors for Relapse in Stage I Seminoma Managed by Surveillance: A Pooled Analysis • Pooled Data of 638 patients(Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) • Median follow-up -7.0 years • Multivariate predictors for relapse: 1) tumor size > 4 cm and 2) invasion of rete testis – If tumor < 4 cm then age less than 30 independent risk factor • Risk of relapse - no risk factors: 12%; one risk factor: 16%; both risk factors: 31% – If tumor < 4 cm, risk relapse if > 30 yo: 11%; if age < 30 yo: 20% Warde et al. J Clin Oncol 2002:4448-4452.
  27. 27. "Long-term outcome of postorchiectomy surveillance for Stage I testicular seminoma." • • • • • • Prospective, single-arm. N=88 20% rete testis invasion, 45% >4cm. Median F/U 12.1 years, 3 lost to follow-up Relapse-free rate: 5-years 83%, 10-years 80%, 15-years 80% Relapse site: 88% (15/17) below diaphragm. Predictor for relapse: invasion of rete testis (HR 3.5, p= 0.03) (Choo R, Int J Radiat Oncol Biol Phys. 2005 Mar 1;61(3):736-40.)
  28. 28. Risk-Adapted Management Prospective. N=314 Median F/U 34 months 100 with no risk factors treated with surveillance 214 patients with risk factors (tumor >4 cm, rete testis involvement) had carboplatin AUC=7 x 2 5-year DFS: surveillance 94%, chemo 96%. Relapses: surveillance 6%, chemo 3% (0.8% if tumor >4cm, 9.1% if rete testis, 6% if both). Median time to relapse 9 months (4-28 months) Aparicio Jet al. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study.J Clin Oncol. 2005 Dec 1;23(34):8717-23.
  29. 29. Prospective. N=227 Median f/u 34 mo 84 pts (37%) with no risk factors treated with surveillance 44 pts (19%) had tumor > 4 cm, 25 (11%) with rete testis, 74 (33%) had both. Only the latter group (both risk factors) received treatment w/ carboplatin x 2. All others received surveillance only. 16 relapses (7%) for pts on surveillance; 1 relapse (1.4%) for pts on carboplatin. 3 yr DFS 88% (surveillance group), 98% (adjuvant carboplatin group). OS 100%. Conclusion: For 2 risk factors: carboplatin. For 0-1 risk factors: observation Aparicio J et al.Risk-Adapted Treatment in Clinical Stage I Testicular Seminoma: The Third Spanish Germ Cell Cancer Group Study. J Clin Oncol. 2011 Oct 31
  30. 30. • Validation study failed to identify rete testis invasion as prognostic on univariate analysis and neither variable was prognostic on multivariate analysis. Chung PW, Daugaard G, Tyldesley S, et al. Program and abstracts of the 46th American Society of Clinical Oncology Annual Meeting; June 4 - 8, 2010; Chicago, Illinois. Abstract 4535 • • Compliance with follow-up is a concern for this patient population. In one study, as many as 21% of patients were lost to follow-up within 5.5 years. Alomary I, Samant R, Gallant V. Treatment of stage I seminoma: a 15-year review. Urol Oncol. 2006;24:180-183.
  31. 31. • Stage I surveillance – – – – – H&P, labs every 3–4 months for 3 years, every 6 months for years 4–7, then annually., CT abdomen and pelvis at each visit. CXR at alternate visits up to 10 years
  32. 32. Adjuvant RT for Stage I Seminoma • • • Historically, seminoma was treated with orchiectomy + inguinal/paraaortic RT, and sometimes also mediastinal RT Prophylactic mediastinal RT was abandoned due to increased cardiac mortality in the 1960's and 1970's Para-aortic fields plus ipsilateral iliac LNs ("dog leg") at 30/15 became standard
  33. 33. Dog-Leg vs. Para-aortic – Randomized. 478 men with Stage I to PA or Dog-Leg. – RT 30 Gy. Median F/U 4.5 years Dog Leg RT 3YR RELAPSE FREE SURVIVAL 96.6% 96% OS 99.3% 100% PELVIC RELAPSE FREE SURVIVAL • Para Aortic RT 100% 98.3% Relapse: 9 in each group (NS), but pelvic recurrences 0 DL vs. 4 PA (Fossa SD, J .MRC.Clin Oncol. 1999 Apr;17(4):1146.)
  34. 34. MRC Trial TE 18, EORTC 30942 RT Dose Randomized trial, N=625 pts Post orchiectomy --- Paraaortic radiation (dogleg for patients with prior inguinal surgery) 20Gy/10 10 30Gy/15 Relapse 11(NS) 2-year relapse rate of 3-4%. 1 death (allocated to 20 Gy) Toxicity: At 4 weeks, 20 Gy significantly better (moderate/severe lethargy 5% vs. 20%); at 12 weeks no difference Jones WG et al.J Clin Oncol. 2005 Feb 20;23(6):1200-8
  35. 35. Other Dose Fractions • • 25.5 Gy /15# /3 weeks, 20 Gy /10# /2weeks results in excellent survival and freedom from relapse Nausea occurs more frequently when a higher daily dose per fraction is delivered Niewald M, et al. Low-dose radiotherapy for Stage I seminoma longterm results. Int J Radiat Oncol Biol Phys 2006;66:1112e1119
  36. 36. Reduction in RT Field size Superior edge of para-aortic field – Retrospective. – 80/163 patients, Stage I seminoma. – Treated with PA field extending from T11/T12 (vs historical T10/T11) to L4/L5. – Median dose 20 Gy. ;Median F/U 7.1 years – Outcome: 5-year RFS 95%; no relapse above T12 – Dosimetry: Median reduction of treated volume 16% (13-21%) – Conclusion: Recommended to minimize risk of radiation-related late effects (Bruns F. Adjuvant radiotherapy in stage I seminoma: is there a role for further reduction of treatment volume?" Acta Oncol. 2005;44(2):142-8.)
  37. 37. Radiotherapy Technique • Position and immobilization – Supine, arms placed by the pt. side and legs straight, with feet stabilized with a foam wedge underneath the knees. – Body cast can also be used for immobilization – Position penis out of field • Shielding – Contra-lateral testis is shielded with a lead clamshell device. Mean dose values to the contra lateral testicle. PA PA + IL iliac Without shield 1.86 cGy 3.89 cGy With shield 0.65 cGy 1.48 cGy
  38. 38. Stage I: • • Field margins – Superior: T11–T12 interspace – Inferior: L5–S1 interspace – Lateral: transverse process – For left testis: cover renal hilum Dose – 20 Gy in 10# to para-aortic ± pelivic lymph node by ap-pa field Elective para-aortic field for stage I seminoma
  39. 39. Nodal CTV and Contouring for Seminoma stage I • Contour the IVC and aorta separately from 2 cm below the top of the kidneys down to the point where these blood vessels end. CTV1 (cm) PTV Block Edge IVC +1.2 +0.5cm +0.7cm Aorta +1.9 Posterior view of para-aortic fields. Wilder RB et al. Radiotherapy treatment planning for testicular seminoma. IJROBP 2012 Jul 15;83(4):e445-52
  40. 40. Adjuvant CT for stage I Seminoma • • Chemotherapy is preferred in patients with a horseshoe (pelvic) kidney, inflammatory bowel disease, or a history of radiotherapy Multiple nonrandomized trials have been published using either a single or 2 cycles of carboplatin.
  41. 41. RT vs. Chemo MRC TE19/EORTC 30982 Randomized multi-national. 14 countries. N=1447, Stage I. Median F/U 4 years Arm 1 1 cycle carboplatin (AUCx7) Arm 2 Radiation (PA or DL ) 20Gy/10 - 30Gy/15). Adjuvant RT Adjuvant CT 3 Yr Relapse Free Survival 95.9% 94.8% Relapse Distant 57 % Pelvic 31 % 74 % Para Aortic Group Second testicular tumors 10 2(SS) - Oliver RT et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 2329;366(9482):293-300
  42. 42. Mature Results on Relapse and Contralateral Testis Cancer Rates in MRC TE19/EORTC 30982 Median FU 6.5 yrs • • RT arm RFS • • Carbo arm 94.7% 96% (HR1.25) 1 death from seminoma in RT arm. Pts receiving >= 99% of the AUC 7 dose had RFS of 96.1% vs 92.6% of those who had lower doses (p=0.08). Reduction of contralateral GCTs with carbo (carbo n=2 vs RT n=15; HR 0.22). Conclusion: confirmed non-inferiority of single dose carboplatin vs RT; reduced risk of 2nd GCT. Criticism - it was designed to exclude a 3% relapse risk in the carboplatin arm- the main goal consequently not being achieved. Oliver RT, J Clin Oncol. 2011 Mar 10;29(6):957-962.
  43. 43. • Increased relapse risk with the single-dose carboplatin regimen, as seen in one prospective study (9% vs 0%) [Dieckmann KP et al : Adjuvant treatment of clinical stage I seminoma: is a single course of carboplatin sufficient?Urology 2000, 55(1):102-6] • Current recommendation is to administer either a single carboplatin dose (that must be properly dosed with the help of renal scintigraphy) or two cycles spaced three weeks apart.
  44. 44. SURVEILLANCE ADJUVANT RT ADJUVANT CT % OF PTS RELAPSING 20 % 4% 1 ×CARBO - 5 -9 % 2×CARBO - 0 – 3 % MEDIAN TIME TO RELAPSE 14 MONTHS 4% @ 5 yrs MC RELAPSE RETRO PERITONEAL NODES 74 -94% DISTANT METS PARA AORTIC NODES 5YR CAUSE SPECIFIC SURVIVAL 99.3% 99 – 100% 9 MONTHS 99- 100%
  45. 45. SEMINOMA STAGE 2 • Depends on bulk of retroperitoneal nodes • Radiotherapy treatment of choice in stage 2a & 2b (node < 5cm), 25 to 35 Gy • Disease specific survival rate 97 – 100% • Reccurance rate < 10% ,MC site SCF & mediastinum. • CT + RT = RT alone (patterson et al, 2001)
  46. 46. Stage II • • • • Superior: T11–T12 interspace Inferior: mid-obturator foramen Lateral: transverse process down to L5–S1 interspace then diagonally to the lateral edge of the acetabulum, then vertically downward to the median border of the obturator foramen For left testis: cover renal hilum Paraaortic and ipsilateral inguinal field for stage II left testicular seminoms, with inclusion of the rental hilus.
  47. 47. Modifed Dog Leg Field "Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter clinical trial." 94 patients RT to para-aortic and high ipsilateral iliac LNs Median F/U 5.8 years Stage IIA (n=66) Stage IIB (n=21) Dose 30 Gy/ 15# 36 Gy/18# 6-year RLF 95% 89% Toxicity: Grade 3 nausea 8-10%; no late toxicity Conclusion: RT for Stage IIA-B seminoma, with reduced portals, yields excellent tumor control and no late toxicity (Classen J, J Clin Oncol. 2003 Mar 15;21(6):1101-6.)
  48. 48. Modified Dog Leg Field cont.. • The German Testicular Cancer Study Group – also support modified field in their prospective trials. [Schmidberger H. 1997, Bamberg M. 1999, Classen J,2003] • European Germ Cell Cancer Consensus Group recommends that the inferior border of dog-leg fields should be placed at the upper border of the acetabulum in patients with no prior history of pelvic surgery.
  49. 49. • Stage II a25Gy in 20 # by AP-PA • Stage II b & IIc 25 Gy in 20 # 10 Gy in 5 # Stage IIb Dog Leg Modified to cover common iliac Boost Field
  50. 50. • • • CTV1 + Iliac vessels down to the upper border of the acetabulum. 1.2-cm expansion on the iliac vessels and included in CTV1. The PTV1 is created as previously described Wilder RB et al. Radiotherapy treatment planning for testicular seminoma. IJROBP 2012 Jul 15;83(4):e445-52
  51. 51. • • • • • Contour the retroperitoneal adenopathy (i.e., the gross tumor volume). GTV + 0.8cm = CTV2 CTV2 + 0.5cm =PTV2 PTV2 + 0.7cm = Block Edge By coning down after 20 Gy, one reduces toxicity. Multileaf collimator blocks for the boost (posterior view).
  52. 52. Chemotherapy for stage IIa & IIb Prospective, non-randomized. 72 pts (18-Stage IIA, 54-Stage IIB) Median f/u 71 m 4 cycles of cisplatin + etoposide 3 cycles of BEP (bleomycin, etoposide, cisplatin). 83% achieved CR, 17% PR. 5-yr PFS 100% and 87% for Stage IIA and IIB. 5-yr OS 95% Conclusion: Chemotherapy is a highly effective and well-tolerated treatment for patients with stage IIA or IIB seminoma (Spanish Germ Cell Cancer Group Garcia-Del-Muro X, J Clin Oncol. 2008 Nov 20;26(33):54165421.)
  53. 53. STAGE 2C • Stage 2c ( node > 5cm) • Systemic chemo is the treatment of choice, RT is a option but relapse rate is 30%. • If nodes > 10 cm RT relapse rate is 40 %. • CT of choice is BEP x 3/EP x 4
  54. 54. Seminoma Stage 3 • Treatment is BEP × 3 cycles or EP × 4 cycles • Einhorn and colleagues demonstrating that the fourth cycle was associated with excess toxicity but with no increased cancer-specific survival salvage surgery Reference N CR% DFS% Einhorn 1989 • Regime BE500P x 4 cycles BE500P for 3 96 98 97 98 92 92 Cisplatin based regimen was superior to the carboplatin arm [Bajorin 1993; Bokemeyer 1996; Horwich 1997; Horwich 2000]
  55. 55. 3 x BEP vs 4 x EP N=270(135 each) E500P x 4 cycles vs B90E500P x 3 cycles To test equivalence primary endpoint of favorable response rate was similar between the 2 arms (97% vs 95%; P = .34) No statistically significant differences were found in 4-year event-free survival (P = .135) or overall survival (P = .096) E500P for 4 cycles arm had more episodes of neutropenia, febrile neutropenia rate (7% vs 5%) and the use of growth factors (36% vs 29%) were equivalent. Neurologic (P = .006) and dermatologic (P =.001) toxicities were more frequent with B90E500P for 3 cycles Culine S, Kerbrat P, Kramar A, et al. Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). Ann Oncol. 2007;18:917-924
  56. 56. Stage II Seminoma IIa IIb RT IIc Chemo
  57. 57. Salvage After CT • Residual mass regress in about a month in 80%. Stage II / III BEP x 3 or EP x 4 Post Chemotherapy residual Mass < 3 cm observe >3 cm well diff Resect /Salvage RT poorly diff observe/Salvage RT
  58. 58. Follow up schedule for seminoma • After RT for stage I seminoma – – – – H&P, labs (AFP, b-HCG, LDH), and CXR every 3–4 months for year 1, every 6 months for year 2, then annually, Pelvic CT annually for 3 years for patients treated with PA-only RT (not needed if PA and pelvic RT)
  59. 59. Stage wise management of Non-seminoma STAGE I Post orchidectomy options are: • Surveillance • RPLND • Chemotherapy
  60. 60. Stage I • • STAGE 1 (50%) Survival close to 100% • Risk factors for relapse • Venous invasion • Presence of undifferentiated elements • Absence of yolk sac elements • Surveillance – Follow up tumor markers, phy examination, cxr monthly 1 yr, 2m – 2 yr, 3m – 3 yr, 6m – 4&5 yr. – CT abd & pelvis monthly for 1 yr, 4m – 2 yr , 6m – 3 yr, yearly 4- 5 yr
  61. 61. • RPLND is offered to stage I nonseminoma patients : 1. with LVI in the primary tumor 2. to noncompliant patients • The presence of (LVI), is associated with a 45% to 55% of recurrence vs 15% to 20% for patients without this risk factor • [Colls 1999; Daugaard 2003; Gels 1995]
  62. 62. Retro peritoneal lymph node dissection(RPLND): • Include the precaval, retrocaval, paracaval, interaortocaval, retroaortic, preaortic, para-aortic, and common iliac lymph nodes bilaterally. Disadv.: • Retrograde ejaculation. • With modern nerve-sparing techniques, the incidence has declined to rates of 5%. Stephenson Aj et al Curr Treat Options Oncol. 2005;6:367-377.
  63. 63. Adjuvant chemotherapy for stage I NSGCT • Failure of postorchiectomy markers to normalize (stage IS) indicates the presence of systemic disease, often outside the retroperitoneum and requires primary management with systemic chemotherapy. [Davis 1994] • Trials evaluating 1 or 2 cycles of bleomycin, etoposide, and cisplatin (BEP) in all T2N0-T4N0 demonstrated continuous disease-free survival and overall survival rates of 95% and 99%, respectively Cullen MH, et al. Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report. J Clin Oncol. 1996;14:1106-1113
  64. 64. NSGCT(STAGE 1) Median time to relapse is 6 month with almost all relapse < 2 yrs. SURVEILLANCE RPLND ADJ CT(BEP *2) RELAPSE RATE 28% 11% 2% DISEASE SPECIFIC SURVIVAL 98% 98 – 99% 99% Recurrence 50 % retroperitoneal nodes, 25% lung Distant sites Retroperitoneal nodes
  65. 65. STAGE IIc /III Chemotherapy (BEP x 4) residual disease salvage surgery Note: - Radiation therapy only for palliation in metastatic disease. Reference Regimen(Cycles) N CR, % DFS, % De Wit 1995* BEP (4) PveB/BEP (4) 118 116 72 76 NR NR De Wit 1998*† BEP (4) VIP (4) 38 46 82 80 79 85 Nichols 1998 BEP (4) VIP (4) 141 145 60 63 64 60 †Trial performed exclusively in nonseminoma, intermediate-risk patients.
  66. 66. Stage I patients are subdivided into low risk, (20% relapse rate) or high risk, (40–50% relapse rate), according to absence or presence of vascular, (lymphatic or venous) invasion.
  67. 67. Salvage Chemotherapy • 20% to 30% of patients will develop progressive disease following initial chemotherapy with or without surgery and will require salvage therapy • Conventional doses of cisplatin plus ifosfamide plus either vinblastine (VeIP) or paclitaxel (TIP) are the most commonly used regimens.
  68. 68. Chemotherapy BEP Bleomycin Toxicity Pulmonary fibrosis Etoposide (VP-16) Myelosuppression Alopecia Renal insufficiency (mild) Secondary leukemia Cis-platin Renal insufficiency Nausea, vomiting Neuropathy
  69. 69. Complications : Radiotherapy • • • • • Acute--nausea, vomiting, diarrhea Late--small bowel obstruction, chronic diarrhea, peptic ulcer disease (<2% with <35 Gy) Second cancers: 5–10% increased risk With testicular shielding, most patients will have oligospermia by 4 months that lasts ~1 year Infertility: 50% of patients have subfertile counts on presentation or after surgery. After RT, 30% able to have children
  70. 70. Conclusion  Most common curable malignancy of young adults.  Seminoma > nonseminoma  Surgery is the main modality of treatment followed by Radiotherapy & or chemotherapy for seminoma and chemotherapy & RPLND for nonseminoma.  Surveillance for patients who are compliant  Follow-up is recommended to detect second primary tumors, local or distant recurrences, and to monitor for potential long-term side effects
  71. 71. Thank you…

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