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The Role Of RPLND In The
Management Of Testis Cancer
Dr Manish I. Patel
Urological Cancer Surgeon
Westmead Hospital
University of Sydney
The Role of RPLND
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•
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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
The Role Of Primary RPLND for NSGCT
• 30% Stage I NSGCT will have occult +RPLN
• High risk Stage I will have >50% +RPLN
• +RPLN- some will require adjuvant chemo BEPX2
– >5 nodes, >2cm, extranodal extension.(43%)
• Despite RPLND some will relapse distantly- 11-34%
– Chemotherapy
• 1% die
• Side effects
– Anejaculation: With templates and nerve dissection=1-5%
– Small bowel obstruction -1-3%
Role of Primary RPLND-NSGCT
Adjuvant Chemo for Stage I NSGCT
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•
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European and Australian Practice:
High risk Stage I NSGCT : >50% risk of relapse
Treat with BEPX2 adjuvant therapy
2% relapse.
1% die
• Side effects:
– Lung, neuropathy, late malignancy
– Late recurrence??
Primary RPLND vs Adjuvant Chemo?
Surgery
Primary RPLND
Adjuvant Chemo
100%
1%
Chemo-2-3 cycles 39%
100%
More cycles
2%
2%
Death
1%
1%
Double therapy
39%
1%
Quality of life
?
?
Who should have primary RPLND?
• Can’t have chemo
• Fertility is very important
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
Post-Chemo NSGCT
Resection 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.
Post-Chemo NSGCT
Resection 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
Surgery for necrosis is not beneficial.
• Need to accurately predict those with necrosis.
• Minimise morbidity of surgery.
Accurately predicting the histology of PC
residual masses has been difficult.
ReHit Study Group
716 PC RPLND Histology from 6 centers.
>90% residual masses >5mm
Histology of mass not resected by various policies
Instit.
Policy
N
Necrosis Teratoma
Cancer
Resect None
716
45%
42%
13%
<10mm or >70%red+ 10 T. -ve
237
72%
23%
5%
Mass <10mm
204
70%
25%
5%
Steyerberg
Prediction model >70% necrosis
Steyerberg JCO 1998 16(1): 269-274
181
81%
13%
7%
Netherlands
Mass < 10mm and 10 T. -ve
114
76%
17%
7%
MSKCC (old)
<10mm + prechemo <=30mm
113
65%
30%
5%
NRH
<20mm+ 10 T. –ve+ prechemo markers
normal
52
88%
4%
8%
Indiana
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%)
<2cm
101
7 (7%)
26 (26%)
2 (2%)
66 (65%)
> 2cm and <5cm
41
3 (7%)
21 (51%)
0
17 (42%)
>5cm and <10cm
17
3 (18%)
10 (59%)
0
4 (24%)
>10cm and <20cm
5
0
3 (60%)
1 (20%)
1(20%)
205
13 (6%)
75 (37%)
3 (2%)
114 (56%)
Total
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%)
>0cm and <0.5cm
12
0
3 (25%)
0
9 (75%)
>0.5cm and <1.0cm
24
0
6 (25%)
0
18 (75%)
>1.0cm and <1.5cm
15
2 (13%)
4 (27%)
1 (7%)
8 (53%)
>1.5cm and >2.0cm
18
2 (11%)
5 (28%)
1 (6%)
10 (56%)
Total
111
4 (4%)
33 (30%)
2 (2%)
71 (64%)
PC-RPLND Good Risk (IGCCCG) Patients
Presence of Teratoma in the Residual RP Mass
Residual Mass <2cm and Histology of Primary Tumor
Residual Retroperitoneal
Mass Size
Teratoma in Primary
Total
Teratoma in
Retroperitoneum
No Mass
+
-
18
23
10 (56%)
5 (22%)
>0cm and <0.5cm
+
-
6
6
1 (17%)
2 (33%)
>0.5cm and <1.0cm
+
-
8
16
2 (25%)
4 (25%)
>1.0cm and <1.5cm
+
-
8
7
3 (38%)
1 (14%)
>1.5cm and >2.0cm
+
-
6
12
5 (83%)
0
Total
+
-
46
64
21 (46%)
12 (19%)
PC-RPLND Good Risk (IGCCCG) Patients
Variables Predicting Necrosis in the
Retroperitoneum
Univariate
Multivariate
P value
Odds Ratio
(95%CI)
P value
Absence of teratoma in the primary
<0.001
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
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
Variable
0.07
• 87 patients with PC
masses <=20mm.
• 23 patients mass<=5mm
• All had RPLND
• Increasing incidence of
teratoma with size of
mass.
•
No significant pre or post
PC factor predicted
necrosis.
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:
Survival=+2 years
with resection of
masses 10-20mm.
Survival=+1 year with
resection of masses
0-10mm.
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 <2cm 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?
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
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, 11:324, 1993
Wood et al. Cancer, 70: 2354, 1992
Management of Post-Chemo
Seminoma Mass.-MSKCC
104 PC
seminomas
Residual mass
<3cm
N=74
Residual mass
=>3cm
N=30
Surgery n=28
Observation n=46
Observation n=3
Surgery n=27
Necrosis=28
Relapsed in RP
N=2
No relapse
Seminoma=6
Teratoma=2
Herr et.al. JUrol 1997 157(3): 860
Puc et.al JCO 1996 14(2): 454
Complete Resection is Important.
All who relapse DOD, All incomplete resections DOD
Management of Post-Chemo
Seminomatous Mass.-Indiana University
21 PC seminoma
residual
mass
Residual mass
<3cm
N=12
NED n=11
relapse n=1
Residual mass
=>3cm
N=9
NED n=8
Relapse n=1
Approx 50% of non-resected masses completely resolved
a median of 12 months form chemotherapy
Schultz et.al. JCO 1990 8(4): 756
Prospective studies show a low relapse rate
for residual masses =>3cm.
DeSantis. JCO 2004; 22:1034-1039
FDG-PET is useful in masses >3cm.
• 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; 22:1034-1039
Suggested management of PC-Seminoma
• PC seminoma residual masses <3cm should be
observed.
• PC seminoma residual masses => 3cm should
be imaged with FDG-PET.
• Complete resection is very important for
outcome.
Antegrade Ejaculation Can Be Preserved After
Lumbar Sympathetic Nerve Sparing During PostChemotherapy Retroperitoneal Lymph Node
Dissection For Testicular Cancer
Manish Patel & Howard Gurney
Department of Urology and Medical Oncology
Westmead Hospital
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.
Only a small number of non-palapable tumors will be
located outside the modified dissection template.
Herr et.al. J Urol. 1992;148(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
– 39=BRPLND. 1 patient had tumor outside modified template.
– 9= modified RPLND. No recurrence with 55month FU.
– 2= lumpectomy. 1 pt had recurrence.
Lumber Sympathetic Nerves Control Ejaculation
Sympathetic chain
Lumber Sympathetic
Nerves
Hypogastric plexus
Nerve sparing:
Dissection of individual sympathetic nerves
Left Sympathetic nerves
Aorta
IVC
Right Sympathetic nerves
Full bilateral Dissection
Prima Site
Size
ry
of
of
Mass Mass
(mm)
L
PA
155
#
AGE?
Nerve
preser
ved
0
N
R
IAC
60
0
N
L
PA/IA 50
C
2
Y
R
IAC/P 70
C
1
Y
Modified Bilateral Dissection
Cancer
side
l
PA
30
r
l
IAC
4 Y
25
25
R
Nerves
preserved AGE
5 Y
4 Y
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
Unilateral template with nerve sparing
Prima Site
ry
of
Mass
Size
of
Mass
(mm)
#
Nerve
preser
ved
AGE?
L
PA
10
3+2
Y
R
IAC
20
3+3
Y
R
IAC
15
3+1
Y
L
PA
15
3+2
Y
Nerve-sparing PC-RPLND is safe.
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
• Ejaculatory status of 81
patients after nerve
sparing PC-RPLND.
• 35 months FU
– 6 recurrences
– 0 in RP.
• This data confirmed by
SD Fossa’s data
BJC 1999 80(1/2): 249-255
Coogan CL.JUrol. 1996; 156(5) :1656-1658.
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.
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.
Histology at Other Sites
Pathology: Other Sites
RP Pathology
Concordance
Cancer
Malignant
Transformation
Teratoma
Necrosis
RP:Tumor
54%
4
2
7
11
RP: Necrosis
80%
2
0
1
12
6
2
8
23
Total
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
PC-RPLND Good Risk (IGCCCG) Patients
Post-operative Complications
All patients
Residual Mass
<2cm
205 (%)
142 (%)
Small Bowel Obstruction
5 (2)
4 (3)
Chylous Ascites
2 (1)
1(1)
Other
2 (1)
0
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)
Complication
Number
Major
Minor