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Testis Cancer
The Management of Residual Masses
Post-chemotherapy
Dr Manish I. Patel
Urologic Oncologist
Westmead Hospital / University of Sydney
Questions to be Answered.
• Do all masses have to be resected or can the histology
be accurately predicted?
• Do normal (or minimal) residual masses in the RP
need resection?
• Is a modified template safe?
• Is nerve sparing safe?
• Is there a place for surgery post salvage chemo?
• When do you resect a post-chemo seminomatous
mass?
• Is there any way to predict the histology?
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.
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: MSKCC
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
Patel et.al. presented AUA 2003
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%)
Patel et.al. presented AUA 2003
• 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.
Indiana University Outcomes of patients with RP disease
who underwent induction chemotherapy
Median FU approx 4 years.
Survival
A: No residual mass (n=78). OBSERVE
5/78 NED patients: recurrent disease. 4/5 in RP
B: Unresectable (n=50). Mainly marker elevation.
C: Residual mass, 10 Teratoma +ve (n=90).RPLND
10 did not have RPLND.
8/86 NED patients relapsed. 6 distant, 2 in RP.
D: Residual mass, 10 Teratoma –ve, <90%
radiographic PR (n=50).RPLND
5/48 NED patients relapsed. 1 in RP
E: Residual mass, 10 Teratoma –ve, >90%
radiographic PR (n=27).OBSERVE
2/23 NED patients relapsed
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 (43%) 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.
• 17/50 (34%) are cNED with no further therapy.
• 6/50 (12%) are NED with further chemotherapy.
Murphy et.al.J Clin Oncol, 11:324, 1993
Wood et al. Cancer, 70: 2354, 1992
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
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.
Frozen section maybe useful during PC-RPLND.
• Does necrosis on frozen-section analysis of a mass after
chemotherapy justify a limited retroperitoneal resection in
patients with advanced testis cancer?
•
HERR, H. W. BJU. 1997; 80(4): 653-657.
• 62 PC-RPLND patients. Underwent modified RPLND if
residual mass showed necrosis only.
• 89% concordance between FS and final parraffin
section.
• 4 false negatives, all specimen confined.
• 6 years media FU: 14 relapses, 1 in the RP.
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.
Management of Post-Chemo
Seminomatous 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.
• 55 patients PC-RPLND
• 23 well defined masses
– 18 C. Resection.(78%)
– 6 positive histology.
• 32 poorly defined mass.
– 14 C. Resection.(44%)
– 2 positive histology.
• Ravi et.al BJU 1999
Advocated not resecting ill
defined masses.
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
Relpase 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
Best Practise.
• Resect all radiographically visible NSGCT
residual masses.
• Consider resecting normal RP if the primary
tumor is teratoma positive.
• Modified template dissection is safe in small
masses in the landing zone.
• Nerve sparing is safe, works and should be
performed where possible.
• Surgery post salvage chemotherapy is very
important.
• There is a place for desperation surgery.
Best Practise.
• Retroperitoneal pathology will not sufficiently
accurately predict histology at other sites.
• 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.