Journal of Cancer Therapy, 2013, 4, 1429-1434
Published Online November 2013 (
Open Access JCT
Is Post Operative Radiotherapy Justified for Completely
Resected Locally Advanced Renal Cell Cancers?
Reham Abdulmoniem1,2, Tarek Haikal3, Hossam Darwiesh3
1Radiation Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Comprehensive Cancer Center, King
Fahad Medical City, Riyadh, Saudi Arabia; 3Medical Oncology Department, Damietta Cancer Institute, Ministry of Health, Damietta,
Received September 9th, 2013; revised October 8th, 2013; accepted October 16th, 2013
Copyright © 2013 Reham Abdulmoniem et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: There is an underutilization of postoperative radiation therapy (PORT) in renal cell carcinoma (RCC) fol-
lowing radical nephrectomy (RN). The main reason for that is the lack of strong evidence and the contradictory data in
the literature regarding its benefit. We aimed to evaluate the efficacy of PORT in locally advanced patients with RCC
following complete resection. Materials and Methods: The patients had RN and at least two of the poor prognostic
factors like lymph nodes involvement (LN+), renal vein invasion (RVI), inferior vena cava invasion (IVCI) and renal
capsule infiltration (RCI) were included in the study. Ninety-four patients were retrospectively evaluated; 56 patient
received PORT 50Gy/25 fractions/5 weeks and 38 patients who did not receive PORT were compared. The LN+, RVI,
IVCI and RCI were documented in 63 (67%), 46 (49%), 30 (32%) and 71 (76%) patients respectively. Results: Eight
patients (14%) in PORT arm developed local recurrence (LR) are compared with 10 patients (26%) for non-PORT arm.
Five-year overall survival (OS) rates were 78% and 70% for PORT and non-PORT arms respectively (p = 0.3), while 5-
year locoregional control (LRC) rates were 88% for PORT arm and 70% for the non-PORT arm (p = 0.05). The IVCI
and LN+ affected OS significantly (p values 0.007 and 0.009) respectively. The RCI and LN+ only affected the LRC
with p values 0.03, 0.04 respectively. Two out of 56 patients (3.5%) received PORT developed intestinal obstruction
which was treated surgically. Conclusion: The PORT decreased the LR rate in high risk locally advanced RCC patients
significantly. The high incidence of distant metastasis offsets this improvement at the level of overall survival.
Keywords: Renal Cell Carcinoma; Locally Advanced; Postoperative Radiation Therapy; Outcomes
1. Introduction
The incidence of RCC, which accounts for 3% of all
adult malignancies, is gradually increasing and consid-
ered as the most lethal carcinoma of the genitourinary
tumors, with >40% of patients dying from their tumor
[1,2]. Seventy percent of patients presented by locally
advanced disease are still potentially curable by RN;
however, LR rate is high for such group of patients [3,4].
The lymph node involvement, renal capsule invasion,
renal vein involvement and inferior venal cava thrombo-
sis are well-known bad prognostic indicators specially if
the patients had 2 or more of these factors [5,6]. Some
retrospective studies showed survival benefit for adju-
vant post-operative radiation therapy [7-10]. However,
this has not been confirmed in prospective randomized
trials, mostly because these trials were performed during
the era of conventional irradiation using old radiotherapy
techniques [11,12]. Theoretically, PORT would improve
the local control in patients with high-risk features. The
use of targeted therapy following RN as adjuvant treat-
ment had improved the survival, and hence the local re-
currence became a real problem especially in patients
with high risk features for local recurrence.
The purpose of the present study was to evaluate the
value of post-operative radiotherapy on local control and
survival in high risk RCC patients for local recurrence
following RN.
2. Materials and Methods
2.1. Inclusion Criteria
The medical records of 230 patients with RCC treated at
Damietta Cancer Institute (DCI) from 1998 to 2006 were
Is Post Operative Radiotherapy Justified for Completely Resected Locally Advanced Renal Cell Cancers?
reviewed. One hundred thirty six patients were excluded
for the following reasons: incomplete hospital records,
early stage disease, second malignancy, incomplete re-
section and distant metastasis at diagnosis.
High risk patient for local recurrence were only se-
lected for analysis. High risk patients were defined as
patients with stage III or IV and having two factors of
following of poor prognostic factors; 1) lymph node in-
volvement, 2) renal capsule invasion, 3) renal vein in-
volvement and 4) inferior venal cava thrombosis. Total
94 patients met the criteria and were evaluated for the
purpose of this study.
2.2. Radiation Therapy Details
The PORT patients were treated as per Institutional pro-
tocol. The patients treated in supine position using verti-
cal, transverse and lateral laser beams for alignment. All
patients were simulated using Philips AcQsim RT CT-
Simulator, with multiple slices taken. The target volume
was limited to the renal bed and para-aortic lymph nodes.
The radiation was delivered with anteroposterior/poste-
roanterior portals to a total dose of 50.4 Gy with a daily
fraction of 1.8 Gy five times per week. After 45Gy spinal
cord was protected by using lead shielding. In right sided
tumors, part of the liver was shielded after 30 Gy. The
mean dose to the small bowel was kept below 45 Gy and
0% of the volume was not allowed above 55 Gy. The
dose was prescribed at the patient’s midplane at the field
central axis. No attempt was done to include the entire
surgical scar in the treated fields. MULTIDATA plan-
ning system was used for dose calculation. Radiotherapy
was administered with megavoltage Elekta Linear accel-
erator machine dual energy using photon beams 6 and 10
MV. Acute and late toxic effects were graded according
to EORTC/RTOG scale.
2.3. Follow-Up
The follow up protocol included physical examination
every 3 - 4 months during the first 2 years, every 4 - 6
months during the following 3 years and once yearly
thereafter. Annual CT chest and abdomen was done dur-
ing follow up or as per patient complaints.
Information about the disease and survival status was
obtained from the clinical records. For any uncertainty,
phone calls were made to patients by the cancer registry
department at our institute; otherwise patients were con-
sidered lost to follow-up and censored at the date of their
last visit for survival calculations.
2.4. Statistical Analysis
The duration of local control was measured from day 1
of treatment to the date of LR or last contact with the
patient. Overall survival was measured from day 1 of
diagnosis till death or the last follow up date.
Statistical package software system for windows was
used for evaluation of the data. Descriptive statistics in-
cluded values and percentages for quantitative data. Sur-
vival curves were obtained with the Kaplan-Meier me-
thod. The log-rank test was used to compare LR-FS and
OS between groups, and a p value of 0.05 was con-
sidered statistically significant. Univariate analyses of the
prognostic features were realized. Factors chosen for the
final model for multivariable analysis were based on the
elimination of non-significant factors on Univariate ana-
lysis. Multivariable regression analyses were performed
to assess the independent impact of factors on the out-
3. Results
The pathology reports showed that 89% of the patients
were renal cell carcinoma and 11% were clear cell car-
cinoma and granular subtypes. Excised tumor sizes ran-
ged from 7 to 23 cm in greatest diameter, with a median
of 10 cm. The pathological grade was G III and IV in
82% of patients. Fifty-five patients had right-sided tumor,
and 39 patients had left-sided tumors. The follow up pe-
riod ranges from 8 to 74 months with 59 months median
value. Fifty six (60%) patient who had received post-
operative radiotherapy (PORT arm) compared to 38
(40%) patients who did not receive PORT (non-PORT
arm). Table 1 shows patients’ characteristics with dif-
ferent prognostic factors in each group of patients. Sixty
patients were male, and 34 patients were females. The
age of the patients ranges from 29 to 71 years with me-
dian age 50 years (52-year in PORT arm and 45-year in
non-PORT arm). Seventy one (75%) patients had RCI
(43 patients in PORT arm and 28 in non-PORT arms).
Forty six (49%) had RVI (31 patients in PORT arm and
15 patients in non-PORT arm). Thirty patients (32%) had
IVCI (19 patients in PORT arm and 11 in non-PORT
arms). Sixty three (67%) patients had LN+ disease (40
patients in PORT arm and 23 in non-PORT arm). As
shown in Table 2, 18 patients (19%) developed LR and
30 patients (32%) developed DM. Nine patients had both
LR and DM. The LR documented in 10 (26%) patients in
non-PORT arm and in 8 (14%) patients in PORT arm. At
the time of analysis, 70 patients (74%) were alive and 55
patients (59%) were disease free.
Using the Kaplan Meier estimate, the 5y-OS and 5y-
LR-FS for all patients were 75% ± 10% and 82% ± 9%
respectively. The prognostic factors studied include RCI,
RVI, IVCI and LN+ in addition to PORT.
3.1. Local Recurrence Free Survival
The 5-year local recurrence free survival rate for PORT
arm was 88% ± 7% compared to 70% ± 11% for the non-
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Is Post Operative Radiotherapy Justified for Completely Resected Locally Advanced Renal Cell Cancers? 1431
Table 1. Patients characteristics.
Prognostic Factor Surgery +
(N = 56)
(N = 38) All
(N = 94)
Age in years
(median value) 52 45 50 NS
39 (70%)
17 (30%)
21 (55%)
17 (45%)
60 (64%)
34 (36%)
Renal Capsule
No invasion
43 (77%)
13 (23%)
28 (74%)
10 (26%)
71 (75%)
23 (25%)
Renal Vein
No invasion
31 (55%)
25 (45%)
15 (40%)
23 (60%)
46 (49%)
48 (51%)
No thrombus
19 (34%)
37 (66%)
11 (29%)
27 (71%)
30 (32%)
64 (68%)
40 (71%)
16 (29%)
23 (61%)
15 (39%)
63 (67%)
31 (33%)
Pathological Type
Renal cell ca
Clear cell carcinoma
Granular cell ca
53 (95%)
2 (3.5%)
1 (1.5%)
31 (82%)
4 (10%)
3 (8%)
84 (89%)
6 (6%)
4 (4%)
Pathological grade
7 (12%)
49 (88%)
10 (26%)
28 (74%)
17 (18%)
71 (82%)
Table 2. Effect of post-operative radiotherapy on disease
and survival status.
Patient groups
Outcome Total No
Surgery + PORT Surgery alone
Local Control
No Recurrence
8 (14%)
48 (86%)
10 (26%)
28 (74%)
Distant Metastasis
No Metastasis
16 (29%)
40 (71%)
14 (36%)
24 (64%)
Overall Survival
44 (79%)
12 (21%)
26 (68%)
12 (32%)
PORT arm with signicant difference; p value 0.05 (Fig-
ure 1).
The following parameters had a statistically signicant
inuence on 5y LR-FS: renal capsule invasion and lymph
node involvement. The probability of 5-year LR-FS in
case of renal capsule invasion were 71% ± 11% compa-
red to 88% ± 8% for patients without RCI (p value 0.03).
The 5y LR-FS for LN+ patients was 73% ± 8% and for
node negative patients were 90% ± 12%; p value 0.04.
The 5y-LR-FS was 78 ± 8% in patients with IVCI vs.
83 ± 10% in patients free from IVCI (p value 0.1). The
renal vein invasion affected the 5y-LR-FS none signi-
ficantly. The 5y LR-FS was 75% ± 9% for patients with
RVI vs. 85% ± 13% for patients without RVI (p value
Figure 1. Local recurrence free survival difference in pa-
tients received post nephrectomy radiotherapy compared to
patients performed surgery alone.
3.2. Overall Survival Results
The 5-year actuarial survival rate for PORT arm was
78% ± 7% compared to 70% ± 10% for the non-PORT
arm. There was no significant difference observed in
terms of 5-year overall survival between the groups with
and without post-operative radiotherapy; p value 0.3
(Figure 2). As shown in Table 3, IVCI showed signifi-
cant lower 5y-OS 50% ± 14% in comparison to 80% ±
9% in patients with no inferior vena cava thrombosis; p
value 0.007. The LN+ was also highly predictive prog-
nostic factor for OS (79% ± 8% in LN negative and 63%
± 12% in LN positive); p value 0.009. On the other hand,
RCI was not affecting 5y-OS significantly with p value
0.6. Also, 5y-OS in the group of patients having RVI
(69% ± 11%) was not significantly different compared to
78% ± 7% in patients without RVI; p value 0.08. In mul-
tivariate analysis, none of the prognostic factors affected
the 5y LR-FS significantly as shown in Table 3. The p
value for the PORT is 0.07 with hazard ratio 0.8 and
confidence interval ranges from 0.7 to 1.0. Analyzing the
factors affecting overall survival, multivariate analysis
showed that both IVCI and LN+ significantly affected 5y
OS with p value 0.2 and 0.1 respectively.
The acute treatment-related toxicities such as abdomi-
nal pain, nausea, vomiting and diarrhea were seen during
radiotherapy. However generally, PORT was well toler-
ated. The serious events related to radiation were only in
the form of intestinal obstruction which was in 2 patients
out of 56 received PORT (3.5%). Only 1 patient required
surgical interference.
4. Discussion
We believe that OS in locally advanced RCC patients
following RN is going to increase with the advent of tar-
geted therapy in next decade, and we are going to see
more loco-regional recurrences and for such patients
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Is Post Operative Radiotherapy Justified for Completely Resected Locally Advanced Renal Cell Cancers?
Open Access JCT
Table 3. The effect of different prognostic factors on the 5-year local recurrence free survival and 5-year overall survival.
Overall survival Local recurrence free survival
Prognostic factor 5y-OS
% ±S D
Univariate analysis
P value
Multivariate analysis
P value/HR (CI)
% ± SD
Univariate analysis
P value
Multivariate analysis
P value/HR (CI)
78% ± 7%
70% ± 10%
88% ± 7%
70% ± 11%
P = 0.07
HR = 0.8
(0.7 - 1.0)
Renal Capsule
No invasion
70% ± 10%
77% ± 11%
71% ± 11%
88 ± 8%
No thrombus
50% ± 14%
80% ± 9%
P = 0.02
HR = 0.66
(0.02 - 1.4)
78% ± 8%
83% ± 10%
Renal Vein
No invasion
69% ± 11%
78% ± 7%
75% ± 9%
85% ± 13%
63% ± 12%
79% ± 8%
P = 0.01
HR = 0.3
(0.1 - 1.2)
73% ± 8%
90% ± 12%
All patients 75% ± 10% 75% ± 10%
Figure 2. Local recurrence free survival difference in pa-
tients received post nephrectomy radiotherapy compared to
patients performed surgery alone.
PORT would be beneficial [13]. The retrospective trials
have shown that radiotherapy improve the local control
following radical nephrectomy. Cuneyt et al., retrospec-
tively reviewed 40 patients [14]. Five-year OS rates were
found 70% in the PORT group and 20% in the non-
PORT group (P = 0.1) and five-year DFS rates were
found 66% in the PORT group and 16% in non-PORT
and difference in both univariate and multivariate analy-
ses (P = 0.045 and P = 0.0007, respectively).
Rafla et al. reported the results of two retrospective
studies, which showed that OS and DFS rates were better
in patients who received PORT [15,16]. Stein et al.,
studied 56 patients with better OS and DFS in the group
of patients received PORT. Five-year OS rates 50% in
PORT and 40% in non-PORT groups respectively [8].
Safwat et al., reviewed 136 patients who underwent RN.
DFS improved significantly by PORT in Univariate and
multivariate analysis. Five-year cumulative risk of LR
reduced from 38% to 22% (p value 0.014). However, in
this study there was no difference in OS by adding PORT
Makarewicz et al. also showed that the PORT reduced
the LR rates from 15.8% to 8.8% in 114 patients with
T3N0 RCC, but there was no significant effect on the OS
rate [17]. However, Gez et al., retrospectively showed
that PORT did not improve the LRC and was accompa-
nied by mild to moderate adverse effects [18].
The prospective randomized trials which that tested
the value of PORT and did not demonstrate an advantage
in receiving radiotherapy were published by Finney [19]
and Kjaer [11,12]. Finney et al. reported five-year OS
rates of 36% in the PORT group and 47% in the non-
PORT group. The LR rates were 7% for both groups.
The Copenhagen Renal Cancer Study Group (CRCSG)
compared PORT 50Gy and non-PORT in patients having
stage II or III renal cancer. There was no significant dif-
ference in DFS rates between the two groups. Forty four
percent of the patients in the PORT group had radia-
tion-related gastrointestinal and hepatic complications
The contradictory data in the literature between the
retrospective and prospective studies regarding PORT
was realized by recently published meta-analysis by
Tunio et al. which included 7 randomized trials [13].
Seven hundred and thirty five patients were analyzed
with pooled results from these trials showed a significant
reduction of LR in patients treated with PORT (P value
0.0001). However, there was no difference in OS (P =
0.29) and DFS (P = 0.14).
WE strongly believe that tailoring PORT for RCC pa-
tients may show a real benefit especially in patients with
poor prognostic factors. In our study, we chose high risk
patients (those with more than one poor prognostic factor;
Is Post Operative Radiotherapy Justified for Completely Resected Locally Advanced Renal Cell Cancers? 1433
RVI, IVCI, LN+ and RCI) for evaluation of PORT ret-
rospectively. Five-year LRC in our study is 82% ± 9%
which is higher than that reported by Safwat et al. [7]
and similar to Aref series [4] and Gez et al. [18]. This is
mainly due to better case selection in our series (inclu-
sion of patients who underwent RN with lymphadenec-
tomy and exclusion of patients with positive surgical
margin or gross residual following surgery). The radio-
therapy improved the local recurrence rate (26% in non-
PORT arm and 14% in PORT arm) however the DM was
29% and 39% in PORT and non-PORT patients respec-
tively. These data is nearly similar to Aref and Maka-
rewicz data. The isolated LRR were observed in 9 (10%)
patients only; six of them in the non-RT arm. Five-year
LRC was worst in the group of patients having RCI and
LN+ with P values 0.03, and 0.04 respectively. These
findings are comparable to studies by Stein, Rafla and
Finney data [8,16,19].
The radiotherapy did not improve OS rates in our
study and this is comparable to all retrospective and pro-
spective studies [12-18]. Five-year OS in PORT arm was
78% as compared to 70% in non-PORT arm (p = 0.3).
The univariate analysis showed that IVCI and LN+
affected the OS with p values 0.007 and 0.009 respec-
tively. These findings were confirmed by multivariate
analysis with p value 0.02 for the IVCI and 0.01 for LN+.
These results are comparable to the studies of Maka-
rewicz et al. [17] and Safwat et al. [7]. The exclusion of
the pathological types and the pathology grade was main-
ly due to unequal distribution of cases between the two
treatment groups.
5. Conclusion and Recommendation
Our study showed the benefit of PORT in reducing local
recurrence in locally advanced RCC. The overall survival
was also better in irradiated patients, but the difference
did not reach statistical significance. The high DM rate
could justify the need for use of adjuvant targeted ther-
apy in such high risk patients. As there are conflicting
data in the literature regarding the value of PORT, multi-
institutional prospective randomized trials using modern
radiotherapy techniques in addition to targeted therapy
are necessary to evaluate the real role of PORT and im-
prove survival in locally advanced RCC patients.
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