Item does not contain fulltext1 september 201

Biermann, K.

Burger, J. W. A.

de Graaf, E. J. R.

de Wilt, J. H.

Doornebosch, P. G.

Grünhagen, D. J.

Verhoef, C.

English

PubMed

J. W. A. Burger

E. J. R. de Graaf

P. G. Doornebosch

D. J. Grünhagen

K. Biermann

J. H. de Wilt

C. Verhoef

Springer - Publisher Connector

LETTER TO THE EDITOR
Local excision of rectal cancer after chemoradiation:
feasibility depends on the primary stage
J. W. A. Burger & E. J. R. de Graaf &
P. G. Doornebosch & D. J. Grünhagen & K. Biermann &
J. H. de Wilt & C. Verhoef
Accepted: 11 February 2010 /Published online: 9 March 2010
# The Author(s) 2010. This article is published with open access at Springerlink.com
Dear Editor,
In the Netherlands, the standard treatment for T2–3 rectal
cancer is a short-course preoperative radiotherapy (5×5 Gy)
followed by total mesorectal excision (TME). The Dutch TME
trial proved that the addition of preoperative radiotherapy to
surgery decreased the 5-year local recurrence rate from 11% to
6%. For patients with locally advanced rectal cancer, a long
course of preoperative chemoradiation therapy is usually
performed (25×2 Gy). This treatment is based on trials by
Bosset and Gerard that demonstrated that the addition of
5-fluorouracil yielded higher response rates and lower local
recurrence rates.
The introduction of neoadjuvant chemoradiation therapy
for locally advanced rectal cancer has also introduced a
dilemma. In approximately 10–15% of patients, a patho-
logical complete response is seen in the resection specimen.
For these patients, a wait-and-see policy may be beneficial,
with regard to both survival and quality of life. However,
preoperative staging of rectal carcinoma after chemoradia-
tion therapy has proven to be inaccurate. Both Hiotis and
Zmora showed that only 25–33% of rectal cancers that had
a complete clinical response indeed had a complete
pathological response. Many surgeons therefore choose to
remove the tumour area by local excision to confirm the
response to chemoradiation therapy pathologically. In a study
by Guerrieri, 196 rectal cancer patients were treated by
neoadjuvant radiation therapy and local excision alone.
Excellent results were reported, even though these surgeons
never performed salvage TME, irrespective of the patholog-
ical T-stage.
Hereby, we present the case of a patient with a clinical
T3–4N0 rectal cancer and a clinical complete response to
chemoradiation therapy that was treated by local excision.
This 74-year-old woman was seen in the outpatient
department with complaints of rectal blood loss and
residual stool. Rectal examination revealed a ventral
tumour, located just above the anal verge. The tumour
appeared mobile, and the vaginal mucosa was intact. At
colonoscopy, a biopsy was taken, revealing a moderately
differentiated adenocarcinoma. A magnetic resonance
imaging (MRI) of the pelvis showed rectal cancer, extending
5–10 cm from the anal verge. The carcinoma invaded the
subserosa and perirectal tissue. Ingrowth in the vaginal wall
could not be ruled out. There was no lymphadenopathy, and
no distant metastases were found after computed tomography
of the abdomen and thorax. The clinical tumour, node, and
metastasis (TNM) stage was cT3-4N0M0.
The patient was scheduled for neoadjuvant chemo-
radiation therapy (25×2 Gy + capecitabine 2 bid 825 mg).
Six weeks after chemoradiation, the response was evaluated
by rectal examination, MRI of the pelvis, endoanal
ultrasound, and rectoscopy. There appeared to be a
complete response, without lymphadenopathy. Only a small
J. W. A. Burger (*) : C. Verhoef
Department of Surgical Oncology, Erasmus MC—Daniël den
Hoed Cancer Center,
P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
e-mail: j.burger@erasmusmc.nl
E. J. R. de Graaf : P. G. Doornebosch :D. J. Grünhagen
Department of Surgery, IJsselland Ziekenhuis,
P.O. Box 690, 2900 AR Capelle aan den IJssel,
The Netherlands
K. Biermann
Department of Pathology, Erasmus MC—Daniël den Hoed
Cancer Center,
P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
J. H. de Wilt
Department of Surgical Oncology, UMC St. Radboud,
P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Int J Colorectal Dis (2010) 25:1141–1142
DOI 10.1007/s00384-010-0920-y
ulcer remained, located centrally in the area where the
tumour was located. Again, no distant metastases were
seen. After discussing the results with the patient, she was
scheduled for local excision of the tumour area by TEM
10 weeks after completion of chemoradiation therapy,
although the tumour area had not been tattooed prior to
chemoradiation therapy. The central ulcer with surrounding
fibrosis was excised with a margin of 1 cm macroscopically
normal mucosa, resulting in a specimen with an area of 6×
5 cm. Standardised pathology revealed a moderately
differentiated adenocarcinoma, infiltrating the muscularis
propria. The area of the ulcer and surrounding fibrosis was
3×2.5 cm. The margins were complete with a minimal
distance of 4 mm, resulting in a R0 ypT2Nx resection.
A salvage TME was proposed, with which the patient
agreed. Since she experienced soiling before treatment, we
decided to perform an intersphincteric rectal amputation
rather than making a low anastomosis. The procedure took
place 18 weeks after the completion of chemoradiation
therapy. The rectum was found to be fixed to the posterior
vagina. The posterior vaginal wall was partially excised,
and the defect closed with sutures.
The pathology report revealed extensive radiation effects
and scar tissue. Notably, a focus of vital adenocarcinoma was
found. It was located in the perirectal fat and had a diameter
of 2 mm. Four perirectal lymph nodes without tumour were
found. The margins were complete. As a consequence, the
pathological TNM stage after chemoradiation therapy was
changed to ypT3N0 rectal cancer.
Although this 74-year-old patient had a clinical complete
response to neoadjuvant chemoradiation, pathological exam-
ination of the specimen revealed a T2 rectal cancer with
complete margins after local excision. Notably, the salvage
TME specimen contained a viable cancer cell nest at a deeper
level, changing the pathological Tstage to T3 rectal cancer. To
our knowledge, no similar case has been reported. We argue
that the local excision of rectal cancer after chemoradiation
carries the risk of leaving behind viable cancer cell nests. This
is probably caused by a scattered regression pattern of rectal
cancer in response to chemoradiation therapy. With regard to
local recurrence, it is often thought that the local recurrence
after a local excision is caused by a concurrent lymph node
disease. However, failure to remove viable cancer cell nests is
likely to play a role in local recurrence as well. Because
resection margins may be complete, these viable cancer cell
nests can easily go unnoticed.
Apart from increasing the risk of local recurrence, the
remaining viable cancer cell nests can also result in
pathological understaging, as was the case in this patient.
The pathological T stage after chemoradiation therapy and
local excision of rectal cancer determines the risk of local
recurrence and lymph node involvement. It is the basis on
which surgeons decide to either adopt an observational
strategy or proceed with a salvage TME. Borschitz and
Bujko reported that local excision of ypT0 rectal cancer is
associated with a 0% local recurrence rate and a 5% risk of
lymph node disease. YpT1 has a 2% local recurrence rate
and an 8% risk of lymph node disease. Therefore, ypT0 and
ypT1 are often seen as candidates for an observational
strategy. On the other hand, ypT2 is associated with a 7%
local recurrence rate and a 28% risk of lymph node disease.
YpT3 is associated with a 21% local recurrence rate and a
55% risk of lymph node disease. Local excision of ypT2 or
ypT3 rectal cancer is therefore usually followed by a
salvage TME. It follows that an accurate pathological
staging after local excision is of the utmost importance.
To avoid this kind of irradical resection, local recurrence,
and pathological understaging after local excision of rectal
cancer, it is imperative that all tissues that were primarily
invaded by the rectal cancer are removed. The circumfer-
ential mucosal margins of the tumour should be marked by
tattooing the edges of the tumour prior to the start of
neoadjuvant chemoradiation therapy. The deep margins
cannot be marked. This means that when the primary T
stage was cT3, a complete resection of the mesorectal layer
deep to the tattooed tumour area is mandatory. Moreover,
the accuracy of preoperative assessment of the depth of
invasion is limited. Therefore, mesorectal excision may also
be advisable for cT2 rectal cancer. Although mesorectal
excision by local techniques is not a standard procedure, it
is feasible, both by TEM and other endoscopic techniques.
It is important to realise that local excision of all tissues that
were primarily invaded by rectal cancer is not feasible if the
primary stage was T4. Moreover, local mesorectal excision
does not result in an adequate lymphadenectomy.
Dear Editor,
We agree that the results of local excision of rectal cancer
after chemoradiation therapy are promising. However, the
case we reported in this letter proves that an accurate
pathological staging can only be achieved if all tissues that
were primarily invaded by the tumour are excised. Therefore,
circumferential margins of the tumour should be tattooed
prior to chemoradiation therapy, and in patients with cT3
rectal cancer, a complete excision of the mesorectal tissue
deep to the tumour area is mandatory. Patients with cT4
rectal cancer or lymph node-positive disease are not good
candidates for local excision.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
1142 Int J Colorectal Dis (2010) 25:1141–1142


Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage

Burger, J W A

de Graaf, E J R

Doornebosch, P G

Grünhagen, D J

Biermann, K

de Wilt, J H

Verhoef, C

EUR Research Repository

LETTER TO THE EDITORLocal excision of rectal cancer after chemoradiation:feasibility depends on the primary stageJ. W. A. Burger & E. J. R. de Graaf &P. G. Doornebosch & D. J. Grünhagen & K. Biermann &J. H. de Wilt & C. VerhoefAccepted: 11 February 2010 /Published online: 9 March 2010# The Author(s) 2010. This article is published with open access at Springerlink.comDear Editor,In the Netherlands, the standard treatment for T2–3 rectalcancer is a short-course preoperative radiotherapy (5×5 Gy)followed by total mesorectal excision (TME). The Dutch TMEtrial proved that the addition of preoperative radiotherapy tosurgery decreased the 5-year local recurrence rate from 11% to6%. For patients with locally advanced rectal cancer, a longcourse of preoperative chemoradiation therapy is usuallyperformed (25×2 Gy). This treatment is based on trials byBosset and Gerard that demonstrated that the addition of5-fluorouracil yielded higher response rates and lower localrecurrence rates.The introduction of neoadjuvant chemoradiation therapyfor locally advanced rectal cancer has also introduced adilemma. In approximately 10–15% of patients, a patho-logical complete response is seen in the resection specimen.For these patients, a wait-and-see policy may be beneficial,with regard to both survival and quality of life. However,preoperative staging of rectal carcinoma after chemoradia-tion therapy has proven to be inaccurate. Both Hiotis andZmora showed that only 25–33% of rectal cancers that hada complete clinical response indeed had a completepathological response. Many surgeons therefore choose toremove the tumour area by local excision to confirm theresponse to chemoradiation therapy pathologically. In a studyby Guerrieri, 196 rectal cancer patients were treated byneoadjuvant radiation therapy and local excision alone.Excellent results were reported, even though these surgeonsnever performed salvage TME, irrespective of the patholog-ical T-stage.Hereby, we present the case of a patient with a clinicalT3–4N0 rectal cancer and a clinical complete response tochemoradiation therapy that was treated by local excision.This 74-year-old woman was seen in the outpatientdepartment with complaints of rectal blood loss andresidual stool. Rectal examination revealed a ventraltumour, located just above the anal verge. The tumourappeared mobile, and the vaginal mucosa was intact. Atcolonoscopy, a biopsy was taken, revealing a moderatelydifferentiated adenocarcinoma. A magnetic resonanceimaging (MRI) of the pelvis showed rectal cancer, extending5–10 cm from the anal verge. The carcinoma invaded thesubserosa and perirectal tissue. Ingrowth in the vaginal wallcould not be ruled out. There was no lymphadenopathy, andno distant metastases were found after computed tomographyof the abdomen and thorax. The clinical tumour, node, andmetastasis (TNM) stage was cT3-4N0M0.The patient was scheduled for neoadjuvant chemo-radiation therapy (25×2 Gy + capecitabine 2 bid 825 mg).Six weeks after chemoradiation, the response was evaluatedby rectal examination, MRI of the pelvis, endoanalultrasound, and rectoscopy. There appeared to be acomplete response, without lymphadenopathy. Only a smallJ. W. A. Burger (*) : C. VerhoefDepartment of Surgical Oncology, Erasmus MC—Daniël denHoed Cancer Center,P.O. Box 2040, 3000 CA Rotterdam, The Netherlandse-mail: j.burger@erasmusmc.nlE. J. R. de Graaf : P. G. Doornebosch :D. J. GrünhagenDepartment of Surgery, IJsselland Ziekenhuis,P.O. Box 690, 2900 AR Capelle aan den IJssel,The NetherlandsK. BiermannDepartment of Pathology, Erasmus MC—Daniël den HoedCancer Center,P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsJ. H. de WiltDepartment of Surgical Oncology, UMC St. Radboud,P.O. Box 9101, 6500 HB Nijmegen, The NetherlandsInt J Colorectal Dis (2010) 25:1141–1142DOI 10.1007/s00384-010-0920-yulcer remained, located centrally in the area where thetumour was located. Again, no distant metastases wereseen. After discussing the results with the patient, she wasscheduled for local excision of the tumour area by TEM10 weeks after completion of chemoradiation therapy,although the tumour area had not been tattooed prior tochemoradiation therapy. The central ulcer with surroundingfibrosis was excised with a margin of 1 cm macroscopicallynormal mucosa, resulting in a specimen with an area of 6×5 cm. Standardised pathology revealed a moderatelydifferentiated adenocarcinoma, infiltrating the muscularispropria. The area of the ulcer and surrounding fibrosis was3×2.5 cm. The margins were complete with a minimaldistance of 4 mm, resulting in a R0 ypT2Nx resection.A salvage TME was proposed, with which the patientagreed. Since she experienced soiling before treatment, wedecided to perform an intersphincteric rectal amputationrather than making a low anastomosis. The procedure tookplace 18 weeks after the completion of chemoradiationtherapy. The rectum was found to be fixed to the posteriorvagina. The posterior vaginal wall was partially excised,and the defect closed with sutures.The pathology report revealed extensive radiation effectsand scar tissue. Notably, a focus of vital adenocarcinoma wasfound. It was located in the perirectal fat and had a diameterof 2 mm. Four perirectal lymph nodes without tumour werefound. The margins were complete. As a consequence, thepathological TNM stage after chemoradiation therapy waschanged to ypT3N0 rectal cancer.Although this 74-year-old patient had a clinical completeresponse to neoadjuvant chemoradiation, pathological exam-ination of the specimen revealed a T2 rectal cancer withcomplete margins after local excision. Notably, the salvageTME specimen contained a viable cancer cell nest at a deeperlevel, changing the pathological Tstage to T3 rectal cancer. Toour knowledge, no similar case has been reported. We arguethat the local excision of rectal cancer after chemoradiationcarries the risk of leaving behind viable cancer cell nests. Thisis probably caused by a scattered regression pattern of rectalcancer in response to chemoradiation therapy. With regard tolocal recurrence, it is often thought that the local recurrenceafter a local excision is caused by a concurrent lymph nodedisease. However, failure to remove viable cancer cell nests islikely to play a role in local recurrence as well. Becauseresection margins may be complete, these viable cancer cellnests can easily go unnoticed.Apart from increasing the risk of local recurrence, theremaining viable cancer cell nests can also result inpathological understaging, as was the case in this patient.The pathological T stage after chemoradiation therapy andlocal excision of rectal cancer determines the risk of localrecurrence and lymph node involvement. It is the basis onwhich surgeons decide to either adopt an observationalstrategy or proceed with a salvage TME. Borschitz andBujko reported that local excision of ypT0 rectal cancer isassociated with a 0% local recurrence rate and a 5% risk oflymph node disease. YpT1 has a 2% local recurrence rateand an 8% risk of lymph node disease. Therefore, ypT0 andypT1 are often seen as candidates for an observationalstrategy. On the other hand, ypT2 is associated with a 7%local recurrence rate and a 28% risk of lymph node disease.YpT3 is associated with a 21% local recurrence rate and a55% risk of lymph node disease. Local excision of ypT2 orypT3 rectal cancer is therefore usually followed by asalvage TME. It follows that an accurate pathologicalstaging after local excision is of the utmost importance.To avoid this kind of irradical resection, local recurrence,and pathological understaging after local excision of rectalcancer, it is imperative that all tissues that were primarilyinvaded by the rectal cancer are removed. The circumfer-ential mucosal margins of the tumour should be marked bytattooing the edges of the tumour prior to the start ofneoadjuvant chemoradiation therapy. The deep marginscannot be marked. This means that when the primary Tstage was cT3, a complete resection of the mesorectal layerdeep to the tattooed tumour area is mandatory. Moreover,the accuracy of preoperative assessment of the depth ofinvasion is limited. Therefore, mesorectal excision may alsobe advisable for cT2 rectal cancer. Although mesorectalexcision by local techniques is not a standard procedure, itis feasible, both by TEM and other endoscopic techniques.It is important to realise that local excision of all tissues thatwere primarily invaded by rectal cancer is not feasible if theprimary stage was T4. Moreover, local mesorectal excisiondoes not result in an adequate lymphadenectomy.Dear Editor,We agree that the results of local excision of rectal cancerafter chemoradiation therapy are promising. However, thecase we reported in this letter proves that an accuratepathological staging can only be achieved if all tissues thatwere primarily invaded by the tumour are excised. Therefore,circumferential margins of the tumour should be tattooedprior to chemoradiation therapy, and in patients with cT3rectal cancer, a complete excision of the mesorectal tissuedeep to the tumour area is mandatory. Patients with cT4rectal cancer or lymph node-positive disease are not goodcandidates for local excision.Open Access This article is distributed under the terms of theCreative Commons Attribution Noncommercial License which per-mits any noncommercial use, distribution, and reproduction in anymedium, provided the original author(s) and source are credited.1142 Int J Colorectal Dis (2010) 25:1141–1142

Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage:feasibility depends on the primary stage

Burger, J.W.

Graaf, E.J. de

Doornebosch, P.G.

Grunhagen, D.J.

Wilt, J.H.W. de

NARCIS 

Local excision of rectal cancer after chemoradiation: feasibility depends on the primary stage.

Burger, J.W.A. (Jacobus)

Graaf, E.J.R. (Eelco) de

Doornebosch, P. (Pascal)

Grunhagen, D.J. (Dirk Jan)

Biermann, K. (Katharina)

Wilt, J.H.W. (Johannes) de

Verhoef, C. (Kees)

Erasmus University Digital Repository

Local excision of rectal cancer afterchemoradiation: Feasibility depends on the primary stage

Radboud Repository

Crossref

Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage: feasibility depends on the primary stage

Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

EUR Research Repository

EUR Research Repository

NARCIS

Erasmus University Digital Repository

Radboud Repository

Crossref

NARCIS