The Role Of RPLND In The Management Of Testis Cancer

1
The Role Of RPLND In TheManagement Of Testis
Cancer

• Dr Manish I. Patel
• Urological Cancer Surgeon
• Westmead Hospital
• University of Sydney

2
The Role of RPLND

• Is there a role for primary RPLND?
• Indications for Post-chemo RPLND for NSGCT
• Post-salvage chemo RPLND
• Desperation RPLND
• RPLND for post-chemo seminoma
• Templates for RPLND
• Nerve sparing RPLND

3
The Role Of Primary RPLND for NSGCT

• 30 Stage I NSGCT will have occult RPLN
• High risk Stage I will have gt50 RPLN
• RPLN- some will require adjuvant chemo BEPX2
• gt5 nodes, gt2cm, extranodal extension.(43)
• Despite RPLND some will relapse distantly- 11-34
• Chemotherapy
• 1 die
• Side effects
• Anejaculation With templates and nerve
  dissection1-5
• Small bowel obstruction -1-3

4
Role of Primary RPLND-NSGCTAdjuvant Chemo for
Stage I NSGCT

• European and Australian Practice
• High risk Stage I NSGCT gt50 risk of relapse
• Treat with BEPX2 adjuvant therapy
• 2 relapse.
• 1 die
• Side effects
• Lung, neuropathy, late malignancy
• Late recurrence??

5
Primary RPLND vs Adjuvant Chemo?
Primary RPLND Adjuvant Chemo
Surgery 100 1
Chemo-2-3 cycles 39 100
More cycles 2 2
Death 1 1
Double therapy 39 1
Quality of life ? ?
6
Who should have primary RPLND?

• Cant have chemo
• Fertility is very important

7
The management of patients with minimal or no
residual mass after chemotherapy for NSGCT is
controversial.What is a residual mass after
chemo?
Pre-chemotherapy
Post-chemotherapy
8
Post-Chemo NSGCTResection of tumor is important.

• Teratoma
• Chemo-resistant (Baniel et al. JCO 1995)
• Resection is curative.
• Unpredictable malignant potential- TMT.
• Late relapse.
• Median relapse time is 5-7 years.-flawed by short
  FU studies.

9
Post-Chemo NSGCTResection of Viable Cancer is
Important.

• Predicitive Factors of Outcome
• In patients with viable cancer on
• Multivariate analysis.
• Complete resection
• Proportion of viable cancer cells
• Good risk IGCCC criteria

• Complete resection for viable GCT
• May be curative
• Prognostic

10
Surgery for necrosis is not beneficial.

• Need to accurately predict those with necrosis.
• Minimise morbidity of surgery.

11
Accurately predicting the histology of PC
residual masses has been difficult.
ReHit Study Group 716 PC RPLND Histology from 6
centers. gt90 residual masses gt5mm Histology of
mass not resected by various policies
Instit. Policy N Necrosis Teratoma Cancer
Resect None 716 45 42 13
Indiana lt10mm or gt70red 10 T. -ve 237 72 23 5
Mass lt10mm 204 70 25 5
Steyerberg Prediction model gt70 necrosis Steyerberg JCO 1998 16(1) 269-274 181 81 13 7
Netherlands Mass lt 10mm and 10 T. -ve 114 76 17 7
MSKCC (old) lt10mm prechemo lt30mm 113 65 30 5
NRH lt20mm 10 T. ve prechemo markers normal 52 88 4 8
12
PC-RPLND Good Risk (IGCCCG) Patients Histology
of Residual Retroperitoneal Mass Size
Residual RP Mass Size Total Cancer Teratoma Malignant Transformation Necrosis

No Mass 41 0 15 (37) 0 26 (63)
lt2cm 101 7 (7) 26 (26) 2 (2) 66 (65)
gt 2cm and lt5cm 41 3 (7) 21 (51) 0 17 (42)
gt5cm and lt10cm 17 3 (18) 10 (59) 0 4 (24)
gt10cm and lt20cm 5 0 3 (60) 1 (20) 1(20)

Total 205 13 (6) 75 (37) 3 (2) 114 (56)
13
PC-RPLND Good Risk (IGCCCG) Patients Histology
of Residual Retroperitoneal Mass Residual Mass
Less Than 2cm
Residual Retroperitoneal Mass Size Total Cancer Teratoma Malignant Transformation Necrosis

No Mass 41 0 15 (37) 0 26 (63)
gt0cm and lt0.5cm 12 0 3 (25) 0 9 (75)
gt0.5cm and lt1.0cm 24 0 6 (25) 0 18 (75)
gt1.0cm and lt1.5cm 15 2 (13) 4 (27) 1 (7) 8 (53)
gt1.5cm and gt2.0cm 18 2 (11) 5 (28) 1 (6) 10 (56)

Total 111 4 (4) 33 (30) 2 (2) 71 (64)
14
PC-RPLND Good Risk (IGCCCG) Patients Presence of
Teratoma in the Residual RP MassResidual Mass
lt2cm and Histology of Primary Tumor
Residual Retroperitoneal Mass Size Teratoma in Primary Total Teratoma in Retroperitoneum
No Mass - 18 23 10 (56) 5 (22)
gt0cm and lt0.5cm - 6 6 1 (17) 2 (33)
gt0.5cm and lt1.0cm - 8 16 2 (25) 4 (25)
gt1.0cm and lt1.5cm - 8 7 3 (38) 1 (14)
gt1.5cm and gt2.0cm - 6 12 5 (83) 0
Total - 46 64 21 (46) 12 (19)
15
PC-RPLND Good Risk (IGCCCG) Patients Variables
Predicting Necrosis in the Retroperitoneum
Variable Univariate P value Multivariate Multivariate
Variable Univariate P value Odds Ratio (95CI) P value
Absence of teratoma in the primary lt0.001 2.8 (1.1-7.2) 0.03
Normal pre-chemotherapy AFP 0.003 2.8 (1.1-7.3) 0.03
Size of residual RP mass 0.001 0.07
Normal pre-chemotherapy HCG 0.107
Pre-chemotherapy RP mass size 0.233
Initial Stage 0.422
Age 0.461
Normal pre-chemotherapy LDH 0.647
16

• 87 patients with PC masses lt20mm.
• 23 patients masslt5mm
• All had RPLND
• Increasing incidence of teratoma with size of
  mass.
• No significant pre or post PC factor predicted
  necrosis.

17
Decision analysis model predicts increased
survival with resection of minimal residual
masses.

• Decision analysis model for estimating survival
  achieved by resection or observation of minimal
  residual masses.

According to the model Survival2 years with
resection of masses 10-20mm. Survival1 year
with resection of masses 0-10mm.
18
What To Do With Post-Chemo Residual Masses?

• Overall incidence of tumor is 44 teratoma
  (36) TMT (2) viable cancer (6).
• Incidence of tumor in residual masses lt2cm is
  35 teratoma (29) TMT (1) viable cancer
  (5).
• In a multivariate analysis, absence of teratoma
  in the primary and normal pre-chemotherapy AFP
  are predictive of necrosis in the RP.
• Observation of minimal/ no residual masses
  results in 5 RP recurrence in 4 years. How much
  later?
• What is an acceptable risk of tumour in the RP to
  necessitate surgery?

19
Complete Resection after Salvage Chemotherapy is
Paramount!

• 580 PC-RPLND at Indiana University.
• 417 after induction chemo.(markers normal)
• 10 viable cancer rate.
• 163 after salvage chemotherapy (markers normal)
• 55 (90) viable cancer rate.
• 53/90 were able to be completely resected.
• 25 had adjuvant chemotherapy only 9 (36) cNED
• 28 had no adj. Chemotherapy 23 (82) cNED
• All incompletely resected patients died.
• Imperative to resect all post-salvage chemo
  masses.
• Must attempt complete resection as post-op Chemo
  does not appear effective.

Fox et.al. JCO 1993 11(7) 1294
20
Desperation Surgery Has A Place.

• When all chemotherapy options have been
  exhausted, surgical resection is an option.
• Solitary RP masses have a much better outcome.
• 2 studies Murphy and Wood.
• 63 patients underwent desperation surgery.
• 50/63 had a complete resection.
• 23/50 (46) are cNED

Murphy et.al.J Clin Oncol, 11324, 1993 Wood et
al. Cancer, 70 2354, 1992
21
Management of Post-ChemoSeminoma Mass.-MSKCC
Surgery n27
Surgery n28
Observation n46
Necrosis28
Relapsed in RP N2
No relapse
Seminoma6 Teratoma2
Herr et.al. JUrol 1997 157(3) 860 Puc et.al JCO
1996 14(2) 454
22
Complete Resection is Important.
All who relapse DOD, All incomplete resections DOD
23
Management of Post-Chemo Seminomatous
Mass.-Indiana University
Relapse n1
NED n11
relapse n1
Approx 50 of non-resected masses completely
resolved a median of 12 months form chemotherapy
Schultz et.al. JCO 1990 8(4) 756
24
Prospective studies show a low relapse ratefor
residual masses gt3cm.
DeSantis. JCO 2004 221034-1039
25
FDG-PET is useful in masses gt3cm.

• FDG PET studies in 51 patients with metastatic
  pure seminoma who had radiographically defined
  postchemotherapy residual masses, were correlated
  with either the histology of the resected lesion
  or the clinical outcome
• Supported by other studies in post induction
  chemotherapy patients.

DeSantis. JCO 2004 221034-1039
26
Suggested management of PC-Seminoma

• PC seminoma residual masses lt3cm should be
  observed.
• PC seminoma residual masses gt 3cm should be
  imaged with FDG-PET.
• Complete resection is very important for outcome.

27
Antegrade Ejaculation Can Be Preserved After
Lumbar Sympathetic Nerve Sparing During
Post-Chemotherapy Retroperitoneal Lymph Node
Dissection For Testicular Cancer

• Manish Patel Howard Gurney
• Department of Urology and Medical Oncology
• Westmead Hospital

28
What type of surgery is required?

• With extensive prechemo disease in the RP, a full
  bilateral dissection is required.
• The incidence of tumor away from the primary
  landing zone or main mass is common. (Donohue
  1982 JUrol 127)
• The dissection may be limited when the prechemo
  disease is minimal and limited to the primary
  landing zone.
• Advantage limited morbidity
• Disadvantage RP recurrence
• Currently performed at Indiana, not MSKCC.

29
Only a small number of non-palapable tumors will
be located outside the modified dissection
template.

• Herr et.al. J Urol. 1992148(6)1812-5
• Studied 113 patients.PC RPLND for initial bulky
  disease.
• Tumor was located outside the boundaries of a
  modified retroperitoneal lymph node dissection in
  14/ 60 with residual disease.
• But tumor was present within a palpable mass in
  6/14 patients.
• If the residual mass was removed and a modified
  retroperitoneal lymph node dissection was
  performed only 8 would have tumor left in the
  retroperitoneum.
• Rabbani et.al. BJU. 1998 81(2) 295-300
• 50 patients undergoing PC-RPLND
• 39BRPLND. 1 patient had tumor outside modified
  template.
• 9 modified RPLND. No recurrence with 55month FU.
• 2 lumpectomy. 1 pt had recurrence.

30
Lumber Sympathetic Nerves Control Ejaculation
Sympathetic chain
Lumber Sympathetic Nerves
Hypogastric plexus
31
Nerve sparingDissection of individual
sympathetic nerves
Left Sympathetic nerves
Aorta
IVC
Right Sympathetic nerves
32
Full bilateral Dissection
Primary Site of Mass Size of Mass (mm) Nervepreserved AGE?
L PA 155 0 N
R IAC 60 0 N
L PA/IAC 50 2 Y
R IAC/PC 70 1 Y
33
Modified Bilateral Dissection
Cancer side PA IAC Nerves preserved AGE
l 30 4 Y
r 25 5 Y
l 25 4 Y
R 35 3 Y
l 15 5 Y
l 45 3 Y
r 35 3 Y
r 25 4 Y
r 20 3 Y
l 25 4 Y
34
Unilateral template with nerve sparing
Primary Site of Mass Size of Mass (mm) Nervepreserved AGE?
L PA 10 32 Y
R IAC 20 33 Y
R IAC 15 31 Y
L PA 15 32 Y
35
Nerve-sparing PC-RPLND is safe.

• Ejaculatory status of 81 patients after nerve
  sparing PC-RPLND.
• 35 months FU
• 6 recurrences
• 0 in RP.
• This data confirmed by SD Fossas data
• BJC 1999 80(1/2) 249-255

Lumber nerve roots spared Antegrade Ejaculation Total Patients
All Right 80 30
3 right 92 12
2 right 67 6
1 right 0 1

All Left 70 20
3 Left 67 3
2 Left 75 4
Bilateral All 80 5
Coogan CL.JUrol. 1996 156(5) 1656-1658.
36
75-89 incidence of necrosis in lung if necrosis
in RP.

• Brenner et.al. JCO 1996 14(6) 1765
• 24 patients with simultaneous PC-RP and chest
  neck resection.
• 6 (25) patients had discordent pathology.
• Toginini et.al. JUrol 1998 159(6) 1833
• 143 patients with simultaneous PC-RP and chest
  resection.
• 77.5 had the same pathological condition in the
  chest.
• 7/40 patients showing RP necrosis has viable
  cancer in their chest.
• Steyerberg et.al.JUrol 1997 158(2) 474
• 159 patients undergoing PC-RP and thoracotomy.
• Neither size nor degree of shrinkage was
  predicitive of chest pathology.
• Necrosis in RP correlated with necrosis in chest
  89.
• Steyerberg et.al. Cancer 1997 79(2).
• 215 patients, 6 centers (ReHit study).-
  Predictors of necrosis.
• no teratoma in primary, normal prechemo markers
  and single unilateral mass.
• RP histology is not sufficiently accurate to
  eliminate the need to resect chest masses.

37
Conclusion

• It is possible to spare ejaculation with post
  chemo-RPLND
• A minimum of 1 nerve needs preservation along
  with the hypogastric plexus to maintain
  ejaculation.
• Templates can be modified based on PC mapping
  studies by Herr et.al. and Rabbani et.al.
• Groups from Denmark, Indiana and MSKCC have shown
  that modified dissections are safe.

38
Histology at Other Sites
RP Pathology Concordance Pathology Other Sites Pathology Other Sites Pathology Other Sites Pathology Other Sites
RP Pathology Concordance Cancer Malignant Transformation Teratoma Necrosis
RPTumor 54 4 2 7 11
RP Necrosis 80 2 0 1 12
Total 6 2 8 23
Univariate analysis of predictors of Necrosis at
Other Sites
Factor P value
Necrosis in RP Histology 0.035
Normal pre-chemotherapy AFP 0.057
Absence of teratoma in primary 0.126
Normal pre-chemotherapy LDH 0.212
Clinical stage 0.368
Normal pre-chemotherapy HCG 0.571
39
PC-RPLND Good Risk (IGCCCG) Patients
Post-operative Complications
Complication All patients Residual Mass lt2cm
Number 205 () 142 ()
Major
Small Bowel Obstruction 5 (2) 4 (3)
Chylous Ascites 2 (1) 1(1)
Other 2 (1) 0
Minor
Atelectasis 3 (1) 2 (1)
Lymphocele 13 (6) 7 (5)
Prolonged Ileus 6 (3) 7 (5)
Blood transfusion 7 (3.4) 1 (1)
Wound Infection 11 (5) 8 (6)
Other 13 (6) 7 (5)