1. Non-seminomatous germ cell tumors of the testis can be managed with surveillance, chemotherapy, surgery such as radical orchiectomy or RPLND, and radiotherapy for brain metastases. 2. Surveillance is indicated for early stage disease while chemotherapy is preferred for advanced stages or elevated tumor markers. 3. RPLND is performed for staging or residual masses after chemotherapy and can preserve ejaculation through nerve-sparing techniques. 4. Prognosis is generally excellent even for advanced stages, though toxicity from treatment needs monitoring.

1. Management of Non Seminomatous
Germ cell tumors of testis
By
Dr Parneet Singh
Moderator- Dr Ritesh Sharma

5. Stage Wise Treatment

12. Treatment Modalities
• Surveillance
• Chemotherapy
• Surgery
• Radiotherapy for Brain mets

13. Surveillance Indications
• Stage 1A
• Stage 1A after RPLND pN0
• Stage 1B for T2 only
• Stage 1B after RPLND pN0
• 1S post chemo complete response markers neg
• IIA post chemo mass <1cm with markers neg
Sturgeon JF Eur Urol 2011
Zuniga BJU Int 2009

14. Surveillance
• 25% to 30% of patients with normal serum tumor markers relapse
during surveillance
• 15% of T1 and 50% of patients with T2 to T4 tumors will relapse.
• <10% of relapses on surveillance for NSGCT occur more than 2 years
after orchiectomy
• Presence of Vascular invasion or embroynal carcinoma or absence of
yolk sac elements is associated with risk of occult nodal disease
• With presence of vascular inavasion relapse rates 50% and without it
15-20%
• Retroperitoneum is the site of relapse in 2/3rd of patients, the lungs
or markers alone in approximately 1/3rd and then in other visceral
sites. de Wit R J Clin Oncol 2006
Daugaard G APMIS 2003
Read et al JCO 1992

15. • A study by Daugaard et al in APMIS 2003
• 1768 patients with range of f/u 19.5 -76 months
• Overall relapse rates 21.4% with 14 deaths
• Upto 95% who progressed did in 12 months
• 60% was in retroperitoneal LN

16. 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 3rd
edition

17. 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

18. 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.
• 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.
M cullen Annals of Oncology 2012

19. • CT is the recommended treatment in the Scottish
Intercollegiate Guidelines Network guidelines 1998
(Scotland)
• The Clinical Oncology Information Network (UK)
guidelines 2000 (England)
• 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 practised in some countries, and
surveillance is favoured in others

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

21. 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).

23. 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

24. 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

25. • 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

26. • 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.

30. • 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 postorchiectomy serum tumor markers
 Solitary retroperitoneal mass less than 2cmin size

31. 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
Krege et al 2008 Eur Ural

32. 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

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

35. 2nd 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 2nd 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

37. Palliative Therapy
• All patients with persistent or recurrent disease should be
given Pallitative CT
• Chemo can be
 Gem+Carbo
 Pacli+Carbo,
 Gem+ Pacli +/- Carbo
 Oral Etoposide daily
Mulherin JCO 2011
Pectasides ANN oncol 2004

39. 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

40. 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

41. 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

42. 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

43. • 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