The sentinel lymph node concept is scientifically correct and is meanwhile largely accepted in many clinics. Nonetheless, in view of the different types and sites of the primaries treated by various clini- cal disciplines, its implementation is beset by many general and clinic-specific problems. Partly because of these same problems, there are also pronounced differences between continentals and countries in the level of general acceptance and the quality of performance.
We owe it to Nieweg, of The Netherlands, that the main advances made in recent years have been distilled and summarized; his summary was pre- sented in part at the Santa Monica Conference held in December 2000.
An overview was subsequently published in the European Journal of Nuclear Medicine in 2001, in which the main points listed below were re- corded.
1. As a rule, the search for the sentinel lymph nodes (SLNs) is easiest to handle in malignant melanoma, and compared with other primaries it is most successful in this condition. In keeping with this, the SLN concept is accepted almost all over the world in melanoma treatment.
Uren et al. (2000 a,b) stressed at the conference that in 25% of their cases malignant melanomas drained to unexpected locations (see Uren et al.
1998, 1999a,b). Uren and his groupstudied 2045 patients within 13 years: in 148 of these cases (7.2%) they found so-called interval nodes (see also Uren et al. 2000 a,b) (nodes between the pri- maries and the SLNs); micrometastases were found in 14% of these nodes. The authors advise surgical removal of such nodes, together with any addi- tional sentinel nodes in the standard basins. In some patients the interval nodes are the only nodes that contain metastases. Dynamic studies can helpto distinguish ªfirst-echelonº lymp h nodes from ªsecond-echelonº nodes, which need not be removed.
The surgeons at the Santa Monica Conference in 2000 were in agreement that a two-fold diagnostic evaluation by means of the gamma-ray detection probe and the blue dye method should be used.
Four studies performed in community hospitals showed that the sentinel node can be identified in 94±98% of cases.
Most American research groups were of the opinion that sentinel node biopsy is now standard in medical care. But there is no consensus on this so far.
In this context it is of interest that Thompson, at the Sydney Melanoma Unit, explained that SLN biopsy is not currently accepted as standard in medical care in Australia (see also Thompson 1997, 1999, 2000).
In most European countries efforts are made to restrict investigative programs for evaluation of the SLN concept to clinical trials (Kroon et al.
1998). In Germany, however, many departments of dermatology within municipal and university hos- pitals have meanwhile integrated the search for the SLN(s) routinely and monitor their patients within regionally administered follow-upprograms.
The main reason for this cautious evaluation of the SLN biopsy in routine treatment procedures is the lack of results obtained in randomized trials.
Morton et al. (2001) have initiated a multicenter randomized melanoma study to evaluate the real and measurable value of regional controls based on the SLN concept in terms of survival. The trial involves 1784 patients being treated or followed up in 16 centers. The SLN has been identified in 94%
of the cases.
Comparative concluding results of this study are not available at present.
The gravity and difficulty of the procedures ap- plied within the SLN node concept can be derived from the results of a 1062-patient melanoma trial presented by Cascinelli. The false-negative rate of 27% at the beginning of the study was depressing for the participating teams, but as the study pro- Chapter 32
Closing Remarks 32
gressed the SLN identification rate and the quality of node evaluation increased satisfactorily.
It is encouraging that in another study investi- gating 812 cases the rate of false-negative cases ranged between zero and 10% in the participating centers. One of the main advantages of carrying out a search for the SLN is the improvement in lo- coregional staging, and with this also support in decisions on adjuvant regimens.
Cascinelli et al. (2000) have published further detailed information. In their study of 892 cases the regional nodal relapse rate was 6%. Multivari- ate analysis revealed the SLN status as the most significant prognostic factor (P=0.000), followed by the thickness of the primary (P=0.001).
Brand new data have been presented by the Amsterdam group (Vuylsteke et al. 2003). The main data are summarized in Table 1. These data confirm that clinical treatment that is in keeping with the SLN concept is absolutely reliable and the survival data seem promising, although it is diffi- cult to confirm the statistical significance of the therapeutic effect in prospective studies.
Blumenthal et al. (2002) also conclude that SLN dissection is reliable and safe, being associated with less morbidity than elective lymphadenec- tomy.
In Morton's series the 5-year survival rates were 90±95% in node-negative cases and 65% in node- positive cases (see also Morton et al. 1999).
2. With regard to breast cancer evaluations, 26 in- vestigators presented their identification rates.
These varied between 79% and 100%. According to Nieweg's report the mean value was 93%.
In addition, 27 research groups published their false-negative rates, which ranged from zero to 33% (median 7%). Nieweg suggests that the false- negative rate should be and can be reduced to
<5%.
With regard to the techniques used for SLN de- tection, he reports that a Swedish multicenter
breast cancer trial using double labeling with blue dye and
99mTc-colloid found the SLN to be positive for cancer by use of the radioactive method alone in 26% and by use of the blue dye method alone in 8%. This important result gives another signal indicating that both methods should be used si- multaneously (see also Chapter 7).
· In the context of the new developments in breast cancer treatment it is easy to understand the wide discrepancies in the degree of accep- tance of the SLN concept in different parts of the world, because on the one hand the well- tried and internationally practiced concept of intraoperative histologically based cancer diag- nosis in frozen sections followed by axillary re- vision (levels I and II) is easy to perform, while on the other hand, those of us who work in ac- cordance with the SLN concept need a secure histo- or cytopathological diagnosis before the SLN labeling procedure is started.
· The SLNs must be very carefully investigated by serial sectioning leading to immunohistochemi- cal investigations.
· In cases with a positive SLN a second operation with axillary revision is an urgent priority and must be carried out immediately.
All these procedures need continuity of interdis- ciplinary cooperation between specialists in nu- clear medicine, surgeons, and pathologists working together to adapt treatment protocols in the light of documented and internationally recognized new knowledge and of their own ex- perience, in order to keep false-negative rates as low as possible.
Discussions about the value of searching for the SLN in high-grade breast cancers (grade III, high S-phase value) still reveal a great deal of contro- versy. At the St. Gallen Conference (1998) the par- ticipants defined low-, moderate-, and high-risk groups of breast cancers and assigned adequate therapy regimens to each of these groups. The fea- Chapter 32 Closing Remarks
500
Table 1. Main, most recent data presented on diagnosis and treatment of malignant cutaneous melanoma by the Amster- dam group (Vuylsteke et al. 2003)
No. of
patients Median
follow-up SLN detection rate
SLN positive rate
False negative rate
5-Year survival
a209 72 months 99.5% 19% 9% 87% 92% 67%
a
