Hanns-Peter Knaebel, Moritz Koch, Tobias Feise, Axel Benner, Peter Kienle
P. Kienle ( u)
Department of Surgery, University of Heidelberg, INF 110, 69120 Heidelberg, Germany
e-mail: Peter_Kienle@med.uni-heidelberg.de
Abstract
In rectal cancer, accurate preoperative staging is essential to adequately select patients for different therapeutic regimes. Endosonography has been proven to be an accurate staging modality in multiple prospective studies. A recent large retrospective study, however, has cast doubt on the actual accuracy of endorectal ultrasound for staging rectal cancer in everyday clinical routines. The results of endosonographic staging of rectal tumours over a period of 10 years at the De- partment of Surgery of the University of Heidelberg are presented. In a first time period, 424 patients with rectal cancer were staged by endosonography and the data recorded prospectively. The examinations were exclusively done by four sur- geons with high experience and scientific interest in endosonography. The second time period comprises 332 patients with rectal tumours (including adenomas) having undergone endosonography by six different examiners after introduction of this staging method into the clinical routine. The data here were analysed ret- rospectively. Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated for the T and N classifications for both series. In the second series, eight factors which have been postulated to influence staging accuracy in the literature were included in a regression analysis in order to identify relevant factors for staging inaccuracies. Accuracy for staging of the T classification was 81% in the first series versus 71.7% in the second series. In the regression analysis of the second series, status post-chemoradiation proved to be the most significant factor for staging inaccuracy (p <0.0002). When excluding all patients having un- dergone chemoradiation, the accuracy for staging of the T classification rose to 76%. A major problem of endosonography in this second series was overstaging;
the T category was overestimated in 76 cases (22.9% of patients). The main error here was overstaging of adenomas as cancerous lesions (45.5% of all adenomas) and T2-cancers as more advanced cancers (42.2% of all T2-cancers). When exclud- ing the adenomas from this analysis, the accuracy increased to 73.5%. Accuracy for staging of the N classification was 76% in the first series versus 71% in the second series. Status post-chemoradiation again was a relevant factor (p <0.0003);
Recent Results in Cancer Research, Vol. 165
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when excluding these patients the accuracy increased to 73%. The accuracy of endosonography for rectal tumours decreases after introduction of the method into the everyday clinical routine. Nonetheless, apart from magnetic resonance imaging with an endorectal coil, rectal endosonography is still the most accurate staging modality for rectal tumours and allows adequate selection of patients for different therapeutic regimes. As the major problem of rectal endosonography is overstaging, more patients are likely to undergo overtreatment rather than under- treatment. Endosonography is inaccurate in staging patients having undergone chemoradiation.
Introduction
Accurate preoperative staging is essential for planning adequate oncologic treat- ment in patients with rectal cancer, as different stages of the disease require dif- ferent therapeutic strategies [1–4]. Early cancer stages in selected patients may be treated solely by local excision without lymphadenectomy [5–8]. Patients with advanced rectal cancer (T3 or T4 and all lymph node-positive cases), on the other hand, are now recommended to undergo neoadjuvant treatment followed by rectal resection with total mesorectal excision. The Swedish and the Dutch Rectal Cancer Trials have both shown that neoadjuvant chemoradiation improves local tumour control in patients with rectal cancer [9, 10].
Endorectal ultrasound has established itself as a reliable staging modality for rectal cancer in the last ten years [1, 2, 11]. However, there is now debate on the actual accuracy of this method in daily practice. Most of the earlier, smaller prospective studies demonstrated impressive results for endosonographic staging in rectal cancer [12–15], but a recent large analysis of 545 patients revealed an accuracy of only 69% for assessing the level of wall infiltration (T classification) in the routine setting [16].
In this chapter we present our own results of endosonographic staging in rectal cancer over a period of over 10 years, focussing on pitfalls of the method. Moreover, we review the literature in order to put this staging modality in perspective to other standard staging modalities.
Patients and Methods
From January 1988 until June 1996, 424 patients undergoing endosonography for
rectal cancer at the Surgical Department of the University of Heidelberg were exam-
ined in a prospective study and documented accordingly. Only patients undergoing
surgery with subsequent pathohistological work-up were included, as pathohisto-
logical staging served as the gold standard to evaluate endosonographic staging
accuracy. Only four surgeons with high experience and scientific interest in en-
dosonography performed the examinations. The results of this study have in part
been published [17] and will therefore only be referred to briefly in this chapter.
After the introduction of rectal endosonographic staging into our daily routine, the overall accuracy of endosonographic staging seemed to decrease. A retrospec- tive analysis was therefore initiated to evaluate the results and to identify possible risk factors for poorer staging results of rectal tumours. Again only patients un- dergoing surgery with subsequent pathohistological work-up were included, as pathohistological staging served as the gold standard. From August 1996 to De- cember 2001, 332 patients fulfilled the inclusion criteria [109 (32.8%) female and 223 (67.2%) male patients]. The average age of these patients was 61 years.
Endosonography was done with a rigid endosonographic probe with a rotating 7 MHz or 10 MHz scanner (Bruel und Kjaer, Type 1846, Bruel u. Kjaer Instruments Inc. Marlborough, MA) which generates a 360
◦image of the rectal wall. The exami- nation was performed in the lithotomy position after cleansing the rectum with an enema. The endosonography device was generally blindly advanced beyond the tu- mour and then slowly withdrawn while scanning. In cases of higher-grade stenosis, a rigid rectoscope was inserted and used to visualise the lumen, thus facilitating the advancement of the endosonography device through the rectoscope. Acoustic cou- pling was achieved with the help of a water-filled balloon placed over the transducer.
Endosonographic T-staging was done according to the criteria of Hildebrandt and Feifel [14] (Table 1). In contrast to that classification, differentiation of T1- cancers from adenomas was done on the basis of their echogenicity: hyperechoic, homogenous lesions were considered benign, whereas hypoechoic, inhomoge- neous lesions were classified malignant [18] (Fig. 1). Staging accuracy was deter-
Table 1. Corresponding histopathologic and endosonographic T category according to Hildebrandt and Feifel
pT category (TNM classification) uT category
pT0 uT0
No evidence for malignant lesion Normal 5-layer structure of rectal wall
pT1 uT1
Tumour infiltrates mucosa or submucosa Inner hypoechoic layer protrudes or is interrupted (mucosa), middle hyperechoic layer is intact
pT2 uT2
Tumour infiltrates muscularis propria Middle hyperechoic layer is perforated (border mucosa/ submucosa), the outer hypoechoic layer (muscularis propria) is infiltrated but not perforated
pT3 uT3
Tumour perforates muscularis propria and Infiltration of outer hyperechoic layer infiltrates perirectal fatty tissue (borders perirectal fatty tissue)
pT4 uT4
Tumour perforates visceral peritoneum or Tumour infiltrates other organs
infiltrates other organs
Figure 1. Endosonographic differentiation of an adenoma (left), which is homogenous and hyperechoic from a T1 cancer (right), which is inhomogeneous and hypoechoic
mined for the T and N category. Sensitivity, specificity, and positive and negative predictive values were calculated for nodal involvement and for different stages of the T classification. Tumours infiltrating other organs were analysed in relation to all earlier tumour stages, as patients with such advanced tumours generally undergo neoadjuvant chemoradiation (uT4 vs. uT1–3). Tumours confined to the rectal wall were compared to tumours having infiltrated beyond the bowel wall be- cause this is relevant for indicating neoadjuvant radiotherapy (short protocol 5×5 Gray, uT1,2 vs. uT3,4). Furthermore the ability to differentiate tumours confined to the mucosa from further progressed tumours (uT1 vs. uT2–4) and the differ-
Figure 2. Endosonographic image of infiltrated lymph node (left image arrow) and possible staging errors
(right image arrow indicating vessels and artefacts) in patients with rectal cancer
Figure 3. Endosonographic image of a beginning uT3 rectal cancer (arrow depicts the beginning infiltration of the outer hyperechoic layer which corresponds to the perirectal fatty tissue)
entiation of adenomas from cancerous lesions (uT0 vs. uT1–4) were analysed, as these may be relevant for indicating local excision versus oncological resection.
Lymph nodes were classified as malignant if they were hypoechoic or had the same echogenicity as the tumour and if they had round or oval borders; size was not used as a criterion for infiltrated lymph nodes [19] (Figs. 2, 3).
To identify possible risk factors for poor staging, all factors complicating or impairing the examination were evaluated [20]. The more common factors were then further analysed in a regression analysis to see whether these had statis- tical influence on the staging results [21]. The parameters tested in the logistic regression analysis are given in Table 2. As status post-chemoradiation is known to significantly influence all staging modalities [22], an additional stratified analysis was done including only patients without pre-staging chemoradiation.
Table 2. Parameters tested for influence on staging accuracy of endosonography in rectal cancer Parameter I Beginning uT3-stage
a(Fig. 3)
Parameter II Cancer arising within an adenoma
Parameter III Tumour not completely traversable, only limited assessment possible Parameter IV Inflammation/desmoplastic reaction
Parameter V Ulceration
Parameter VI Mucinous differentiation
Parameter VII Status post-probe excision within last 2 weeks Parameter VIII Status post-chemoradiation
a
