We therefore combined the efforts of the CCAFU (Oncology Committee of the French Association of Urology), the UroCCR network, and expert European centers to increase the likelihood of assembling a cohort large enough to address this question.
This European multicenter study (PEMET) investigated peritoneal recurrence (PREC) following nephrectomy for localized renal cell carcinoma (RCC), an uncommon but clinically meaningful pattern of disease relapse. The primary objective was to determine the incidence, patterns of occurrence, associated factors, treatment strategies, and prognosis of PREC.
Using prospective databases from 10 European centers (1987–2023), 117 patients who developed PREC after partial or radical nephrectomy were identified. The overall incidence of PREC was below 1% (0.88%) among nearly 8,000 nephrectomies. The median time to recurrence was approximately 16 months after surgery. Despite its rarity, PREC is associated with substantial morbidity and mortality, emphasizing the importance of understanding its underlying mechanisms and optimal management strategies.
Our findings highlight the existence of two distinct clinical presentations of PREC. The majority of cases were associated with synchronous metastases at other sites (mPREC) (70% of cases), reflecting systemic tumor dissemination and aggressive tumor biology. In contrast, approximately one-third of patients presented with isolated peritoneal recurrence (iPREC), characterized by a more favorable prognosis and, in selected cases, long-term disease control following surgical resection. Patients with iPREC more frequently underwent minimally invasive surgery and partial nephrectomy, had lower tumor stage, lower ISUP grade, and lower Leibovich risk scores, suggesting a different biological and clinical trajectory compared with mPREC.
Although multivariable analysis identified tumor aggressiveness, as reflected by the Leibovich score, as the only independent factor associated with iPREC, the observed associations with surgical approach, partial nephrectomy, and positive surgical margins raise the hypothesis that surgical factors may contribute to peritoneal tumor seeding in a subset of patients. Transperitoneal minimally invasive surgery, tumor manipulation, pneumoperitoneum, and microscopic or macroscopic capsular breach may facilitate local dissemination of tumor cells into the peritoneal cavity. While our data do not allow definitive conclusions, they support the concept of dual mechanisms of PREC: one primarily driven by tumor biology and systemic spread, and another potentially influenced by local, surgery-related factors.
From a therapeutic perspective, most patients with PREC required systemic treatment, reflecting the advanced nature of the disease in many cases. However, the excellent outcomes observed in selected patients with limited iPREC treated with metastasis-directed surgery underscore the potential value of aggressive local treatment in carefully selected cases. These findings support the role of individualized management strategies and reinforce the importance of multidisciplinary decision-making.
This study has inherent limitations related to its retrospective design and the rarity of the event studied. Nevertheless, it represents one of the largest multicenter series focusing specifically on peritoneal recurrence after localized RCC surgery, with long-term follow-up and detailed surgical data. Importantly, it generates clinically relevant hypotheses and highlights a potentially modifiable factor—surgical technique—that deserves further investigation.
In conclusion, peritoneal recurrence after surgery for localized RCC is rare but heterogeneous in presentation and prognosis. Recognizing distinct patterns of PREC may help refine postoperative surveillance, guide therapeutic decisions, and improve surgical quality standards. Prospective studies are warranted to better elucidate the interplay between tumor biology and surgical factors in the development of this atypical recurrence pattern.
Written by: Caroline Pettenati,1,2 Jean-Christophe Bernhard,2,3 Zine-Eddine Khene,2,4 Umberto Capitanio,5,6 Giacomo Musso,5,6 Laurence Albiges,2,7 Larissa Rainho,7 Gaëlle Margue,2,3 Thibault Waeckel,2,8 Gregory Verhoest,4 Lucas Bento,9 Nicolas Doumerc,2,9 Louis Surlemont,10 Yann Neuzillet,11 Thierry Lebret,11 Niels Graafland,12 Saeed Dabestani,13,14 Axel Bex,12,15 Morgan Rouprêt,2,16 Karim Bensalah,3 Pierre Bigot,2,17
- Department of Urology, Hôpital Franco-Britannique, Cognacq-Jay Foundation, Levallois-Perret, France
- Cancer Committee of the French Association of Urology (CCAFU)
- Department of Urology, Pellegrin University Hospital, Bordeaux, France
- Department of Urology, University Hospital of Rennes, Rennes, France
- IRCCS San Raffaele Scientific Institute, Urological Research Institute (URI), Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
- Department of Medical Oncology, Gustave Roussy Cancer Campus, Paris-Saclay University, Villejuif, France.
- Department of Urology, University Hospital of Caen, Caen, France
- Department of Urology, University Hospital of Toulouse, Toulouse, France.
- Department of Urology, University Hospital of Rouen, Rouen, France.
- Department of Urology, Hôpital Foch, Versailles - Saint-Quentin-en-Yvelines University, Suresnes, France
- Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Department of Urology, Kristianstad Central Hospital, Region Skane, Kristianstad, Sweden
- Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden
- Department of Urology, Royal Free London NHS Foundation Trust, University College London, Division of Surgery and Interventional Science, London, United Kingdom
- Department of Urology, AP-HP, Hôpital La Pitié-Salpétrière, Sorbonne University, Paris, France.
- Department of Urology, University Hospital of Angers, Angers, France