Risks of Organ Preservation in Rectal Cancer: Data From Two International Registries on Rectal Cancer
Authors: Fernandez Laura M. , São Julião Guilherme P. , Santacruz Carlos Cerdan , Renehan Andrew G. , Cano-Valderrama Oscar , Beets Geerard L. , Azevedo Jose , Lorente Blas F. , Rancaño Rocío S. , Biondo Sebastiano , Espin-Basany Eloy , Vailati Bruna B. , Nilsson Per J. , Martling Anna , Van De Velde Cornelis J.H. , Parvaiz Amjad , Habr-Gama Angelita , Perez Rodrigo O. ,   on behalf of the International Watch & Wait Database Consortium (IWWD) and the Spanish Rectal Cancer Viking Consortium (VIKINGO), Antona Francisco Blanco , Martín Elena Yagüe , Tébar Jesús Cifuentes , Calvo Alberto Parajó , Quintana Natalia Uribe , Alonso Mauricio García , Cotoré Jesús Paredes , Riesco Ana Benítez , Cánovas Noelia Ibañez , Sanchez Camen Martinez , Ribe i Serrat Didac , Ais Guillermo , Jiménez Toscano Marta , Climent Antonio , Reig Pérez Monica , Sierra Grañón José Enrique , Mateo Janire , Biondo Sebastiano , Saldaña Ana Gálvez , Laso Carlos Álvarez , Allende Ignacio Aguirre , Álvarez Daniel Huerga , Coll Ramón Farrés , Sánchez Bautista Wilson M. , Torres Sánchez Maria Teresa , Dujovne Paula , Camps Ignasi , Cuadrado Marta , Díaz Olga Maseda , Sánchez Nieves , de la Vega Olías Maria del Coral , Basan Eloy Espin , Carre Miquel Kraft , Aghili Mahdi , Arnold Marion , Asoglu Oktar , Bujko Krzysztof , Caiado André , Carvalho Carlos , Chautems Ronald , Coco Claudio , Chiloiro Giuditta , Cunningham Chris , Custers Petra , Haak Hester , D'Hoore André , Dimofte Gabriel , Ding Peirong , Duff S. , Felicio Natalia , Figueiredo Nuno , Gaertner Wolfgang , Gérard Jean-Pierre , Gama-Rodrigues Joaquim , Geubels Barbara , Gregory Ellen , Salazar Ivana P. , Herrando Ignacio , Hill J. , Huq Z. , Jacquinot Frederique , Jakobsen Anders , Jensen Lars Henrik , Jones D. , Keshvari Amir , Ketelaers Stijn H.J. , Khan U. , Kushwaha R. , Kordnejad Shahrzad , Leitner Kurt , Madoff Robert , Malcomson Lee , Martling Anna , Fechner Katja , Matzel Klaus E. , Mazzarisi Claudia , Meershoek Elma , Melenhorst Jarno , Nouritaromlou Mohammed , Paolo Goffredo , Pennings Alexander , Murad-Regadas Sthela M. , Pandini Rafael , Peeters Koen C.M.J. , Rawat S. , Richards D. , Rosa Isadora , Rossi Gustavo , Rutten Harm J.T. , Sanchez Loria Fernando , Santiago Ines , Siddiqui K.H. , Solkar M.H. , Sun Myint Arthur , Telford K. , Tang J. , Temmink Sofieke , Tokmak Handan , Vaccaro Carlos A. , Ward S. , Wolthuis Albert M. , Wytze Lameris , Yu Jiehai , Zhang Zhen 
Published: October 2024

PURPOSE
Organ preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response.

METHODS
Data from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with ≤10% cancer cells—nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM.

RESULTS

Five hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8%
v
10.2%;
P
≤ .001). Independent risk factors for DM included LR (
v
TME at reassessment;
P
= .001), ypT3-4 status (
P
= .016), and ypN+ status (
P
= .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75%
v
87%;
P
= .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages (
P
≤ .009).

CONCLUSION
Patients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes.