Non seminoma germ cell tumor management.pptx

Non seminoma germ cell tumor management.pptx

1. Management of Non Seminomatous Germ cell tumors of testis

2. Stage Wise Treatment

3. Treatment Modalities

4. Surveillance Indications Sturgeon JF Eur Urol 2011 Zuniga BJU Int 2009

5. Surveillance

6. Surveillance de Wit R J Clin Oncol 2006 Daugaard G APMIS 2003 Read et al JCO 1992

7. Prospective trials of Surveillance in Stage 1 Author No of Patients Progression rate(%) Death from disease RP Progression rate(%) Freedman et al 259 32 3 55 Jacobsen et al 83 28 nil 65 Peckhman et al 132 27 1 60 Read et al 396 25 5 61 Sogani et al 102 25 3 72 Sharir et al 170 75 1 65 Gunderson Tepper 3 rd edition

8. SURVEILLANCE Benefits Drawbacks Excellent cancer cure rate Requires frequent follow-up CT scans, with associated long-term risks No treatment-related toxicity Some patients may experience anxiety related to risk of recurrence Excellent salvage rate Avoids overtreatment for the majority of patients

9. Chemo vs Surveillance 2 cycles of BEP vs surveillance in stage I The 2-year recurrence-free survival was 98% in both arms Long-term toxicity was assessed by pre and post-treatment analysis of renal function, lung function, semen analysis, and audiometry . MCullen Annals of Oncology 2012

10. No major, clinically significant changes were observed. This demonstrates that the major toxic effects associated with BEP chemotherapy ( renal,lung , hearing, fertility) were mild or absent following two cycles. CT is the recommended treatment in the Scottish Intercollegiate Guidelines Network guidelines 1998 (Scotland) The Clinical Oncology Information Network (UK) guidelines 2000 (England)

11. The ESMO guidelines 2008 and the European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer 2008 (Europe) The National Comprehensive Cancer Network guidelines 2008 (USA) However, RPLND is still practiced in some countries, and surveillance is favored in others

12. Surgery Orchiedectomy Retro Peritoneal Lymph node Dissection (RPLND) For Residual Retroperitoneal Mass

13. Radical Orchiectomy Radical orchiectomy is done for testicular tumor Done by inguinal incision to prevent alteration of the lymphatic drainage pattern of the testicle ( drainage to the retroperitoneal lymph nodes) by violating the scrotal wall (drainage to the superficial inguinal lymph nodes). Ligation of the vas deferens and testicular vessels at the internal inguinal ring, so no further need of inguinal canal exploration if RPLND to be done(therapy or staging).

14. Indications for RPLND Stage 1A Stage 1B IIA,IIB upfront, marker negative IIA,IIB post chemo marker negative Post Chemo metastatic NSGCT with residual retroperitoneal mass with marker neg Stephenson AJ JCO 2005

15. RPLND RPLND done for diagnostic and therapeutic intent RPLND can be done either by thoracoabdominal or a transabdominal approach. Bilateral infrahilar RPLND has replaced the suprahilar dissection and is the standard Suprahilar dissection is done for residual hilar or suprahilar masses following chemotherapy for advanced-stage NSGCT A bilateral infrahilar RPLND includes the precaval , retrocaval , paracaval , interaortocaval , retroaortic , preaortic , para -aortic, and common iliac lymph nodes bilaterally. Chang SS J Urol 2002

16. Ipsilateral gonadal vein and surrounding fibro adipose tissue till the internal ring must be completely excised to minimize the possibility of a late paracolic recurrence Modified RPLND templates maximize rates of ejaculation by limiting dissection areas of reduced risk of metastatic spread. This approach minimizes contralateral dissection, thereby reducing trauma to the hypogastric plexus and contralateral postganglionic sympathetic fibers. Preservation of antegrade ejaculation with this approach ranges from 50% to 80%. Chang J Ural 2002

17. Nerve-sparing techniques to preserve ejaculation. For right-sided tumors, the interaortocaval nodes and paracaval nodes are removed, with preservation of the left sympathetic chain For left-sided tumors, the para -aortic and interaortocaval nodes are removed and the right autonomic chain is preserved. If significant lymphadenopathy is revealed at surgery, a more extensive surgical resection is performed.

18. JCO 2007 Chemotherapy is preferred for Elevated post- orchiectomy serum tumor markers Retroperitoneal LN greater than 2 cm Involving multiple nodes RPLND is preferred modality for Normal post-orchiectomy serum tumor markers Solitary retroperitoneal mass less than 2cmin size

19. Residual Retroperitoneal Mass Post chemo residual masses with normal serum markers Should be done 4 to 6 weeks after chemo On histology 50% show necrosis 35% are mature teratoma 15 % have malignant disease

20. Complications of surgery Minor complications include Lymphocele (30-40%) Atlectasis (25-30%) Wound infection(10%) Prolonged ileus . Long-term morbidity with a standard bilateral RPLND has been retrograde ejaculation(50-60%) and subsequent infertility secondary to sympathetic nerve fiber damage. Mortality rate of less than 1% Major complications such as hemorrhage, ureteral injury, bowel obstruction, pulmonary embolus, and wound dehiscence are rare. Shienfeld urology 2007

21. Chemotherapy Indications IA ,IB IIA,IIB III Stage I,II post RPLND with pN1-pN3 All stages marker positive Relapse Metastatic disease NCCN 2015

22. 2 nd Line Therapy for Metastatic Disease Patients not having complete response or recurrence Second line chemo can be conventional dose and high dose Ct followed by ASCT After 2 nd line CT if no complete response then disease is usually incurable Except if there is solitary site of metastasis which can be surgically removed Favorable factors Unfavorable Factors Testicular primary site Incomplete response Prior complete response High level of tumor markers Low serum tumor markers Extra testicular tumor Low volume disease Lorch JCO 2010

23. Palliative Therapy All patients with persistent or recurrent disease should be given Pallitative CT Chemo can be Gemcitabine + Carboplatin Paclitaxel + Carboplatin Gemcitabine + Paclitaxel +/- Carboplatin Oral Etoposide daily Mulherin JCO 2011 Pectasides ANN oncol 2004

24. Chemotherapy Complications Nausea ,vomiting Alopecia Myelosupression Pulmonary fibrosis (Bleomycin Toxicity)- fatal in 1 to 2% cases. Secondary leukemia ( Etopside ) :relative risk of leukaemia induced by standard doses of etoposide is 2% Infertility is seen in around 60-70% with bleomycin Kollmannsberger C et al.J Cancer Res Clin Oncol1998

25. Cisplatin : Nausea, vomiting Hearing impairment(22%) Raynaud phenomenon (39%) Ischemic heart disease Renal insufficiency(15%) Sensory Neuropathy (10–30% ) BEP causes immediate azoospermia , but, with time, more than half of patients may recover normal or near-normal spermatogenesis. Paternity rate following 2 to 4 cycles of BEP is 70% to 85%. . Nuver JCO 2005

26. Brain Metastasis Prognosis of brain mets poor Primary CT with CDDP in patients with brain mets with radiotherapy If feasible surgical resection of mets should be done

27. 5 year Survival Stage I nonseminoma has a 5-year OS of approximately 99%. Surveillance has 30% relapse rate RPLND has a10% relapse rate Stage II nonseminoma , the 5-year OS is around 98%. For stage IIA disease Chemotherapy (<5% relapse rate) RPLND plus chemotherapy (<5% relapse rate) is used. Stage IIB or IIC disease, chemotherapy is given, with a 5% relapse rate. Stage III disease is managed with chemotherapy(20-25%) Stephenson AJ BJU 2009

28. The good-prognosis group (60% of cases) has an approximately 86% 5 year OS. The intermediate prognosis group (26% of cases) has an approximately 80% 5 year OS. In the poor-prognosis group (14% of cases), the 5 year OS is around 50 Huyghe Cancer 2004

29. Summary