Diagnostik, Therapie und onkologisches Outcome bei zervikalen CUP-Syndromen je nach p16-Status

Zusammenfassung

Einleitung

Die Inzidenz zervikaler Plattenepithel (SCC)-CUP-Syndrome steigt mit einem relevanten HPV-assoziierten Anteil. In dieser 10 Jahre umfassenden retrospektiven Studie wurden klinische und therapeutische Parameter von Patienten mit zervikalen SCC-CUP erfasst. Neben einer Analyse der Primärtumordetektionsrate bei initialem SCC-CUP (SCC-CUP_init) wurde das mittlere Gesamtüberleben sowie das rezidivfreie Überleben bei Patienten ohne Primärtumordetektion nach erweiterter Diagnostik, also definitiven SCC-CUP (SCC-CUP_def), in Abhängigkeit vom p16-Status ausgewertet, um therapeutische Empfehlungen abzuleiten.

Ergebnisse

Bei 85% (n=131/155) der CUP_init handelte es sich histologisch um SCC, gefolgt von Adenokarzinommetastasen bei 7% (n=10/155). Bei 41% (n=54/131) der Patienten mit SCC-CUP_init wurde mittels erweiterter Diagnostik ein Primärtumor identifiziert; die Primärtumordetektionsrate war dabei bei p16-positiven vs. p16-negativen signifikant höher (63% vs. 23%, p<0,001). Die PET-Bildgebung wies eine Sensitivität bzw. Spezifität von je 73% auf. SCC-CUP_def wurden vorrangig primär chirurgisch mit adjuvanter Radio(chemo)therapie behandelt, SCC-CUP_def-Patienten mit positivem vs. negativem p16-Status wiesen ein signifikant längeres Gesamtüberleben auf (53 vs. 41 Monate, p=0,037), ebenso Patienten mit cN1- vs. cN3-Status und M0- vs. M1-Status.

Fazit

Der p16-Status beeinflusst bei Patienten mit SCC-CUP die Diagnostik und Therapie: Bei p16-positiven SCC-CUP_init gelang signifikant häufiger eine Primärtumordetektion als bei p16-negativen SCC-CUP_init. Bei Patienten mit SCC-CUP_def war ein positiver p16-Status mit einem besserem Gesamtüberleben assoziiert, die Unterschiede rechtfertigen jedoch bislang keine Therapiedeeskalation.

Abstract

Introduction

The incidence of cervical squamous cell carcinoma (SCC)-CUP is increasing, with a significant proportion being HPV-associated. In this 10-year retrospective study, we analyzed clinical and therapeutic parameters of patients with cervical SCC-CUP. Primary tumor detection rates in patients with initial SCC-CUP (SCC-CUP_init) were assessed and mean overall survival and disease-free survival of patients without primary tumor detection after an extended diagnostic workup, i.e. definitive SCC-CUP (SCC-CUP_def), were analyzed taking p16-status into account to derive therapeutic recommendations.

Results

85% (n=131/155) of patients with CUP_init, presented with SCC followed by adenocarcinoma metastases in 7% (n=10/155). In 41% (n=54/131) of patients with SCC-CUP_init, a primary tumor was identified after an extended diagnostic workup; the primary tumor detection rate was significantly higher in p16-positive compared to p16-negative cases (63% vs. 23%, p<0,001). PET imaging specificity was 73% for both sensitivity and specificity. SCC-CUP_def were primarily treated surgically with adjuvant radio(chemo)therapy. SCC-CUP_def patients with positive vs. negative p16-status had significantly longer overall survival (53 vs. 41 months, p=0,037), as well as patients with cN1- vs. cN3-status and M0- vs. M1-status.

Conclusion

p16-status influences diagnosis and therapy response in patients with SCC-CUP: in p16-positive SCC-CUP_init, primary tumor detection rates were significantly higher than in p16-negative SCC-CUP_init. In patients with SCC-CUP_def, p16-positivity was associated with improved overall survival, albeit to an extent which does not justify therapy de-escalation.

Schlüsselwörter

zervikales CUP-Syndrom - Plattenepithelkarziom des Kopf-Hals-Bereichs - p16-Status - Therapie - Prognose

Keywords

CUP syndrome - HNSCC - p16-status

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