Surgical Management of Advanced Pelvic Cancer. Группа авторов
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Locally Recurrent Rectal Cancer
The incidence of locally recurrent rectal cancer (LRRC) remains approximately 5%. A negative resection margin, the most important predictor of outcome, may be difficult to achieve due to the anatomical location, involvement of surrounding structures, and the challenges of prior surgery. As a result, upfront chemoradiotherapy may downstage tumors and improve resectability. In patients who have received radiotherapy for treatment of their primary tumor, reirradiation options are limited. Induction chemotherapy has been proposed as a potential means of improving tumor downstaging and clear margin rates. Moreover, it may eradicate occult micrometastases. Development of metastatic disease is common following local recurrence and represents the leading cause of cancer‐related death following successful treatment of local recurrence. Preliminary results of a cohort study in the Netherlands demonstrated R0 and pCR rates of 55 and 17% respectively with induction chemotherapy compared to 49 and 4% with CRT alone (p = 0.506 and p = 0.015 respectively) [57, 74]. Among the induction chemotherapy group, achieving a pCR was strongly associated with improved three‐year DFS (both local recurrence and distant metastases). Two European prospective randomized trials, the French GRECCAR15 and the Dutch PelvEx2 Induction Chemotherapy Trial, aim to determine the optimum preoperative management for LRRC (NCT03879109, Dutch Cancer Society no. 12960/2020–1). GRECCAR15 is comparing induction FOLFIRINOX (six cycles) followed by CRT (30.2 Gy with capecitabine) to induction FOLFIRINOX alone. The primary outcome of interest is the R0 resection rate.
Future Developments
Long‐term outcome data following induction or consolidation chemotherapy are lacking, and whether the total neoadjuvant approach can improve survival remains to be elucidated. Several prospective randomized trials are currently ongoing to evaluate long‐term disease‐specific outcomes, including the PROSPECT and TNTCRT trials [75]. The awaited North American PROSPECT trial will show us if some high‐risk patients who respond well to induction FOLFOX can omit neoadjuvant radiotherapy. GRECCAR12 (lower‐risk patients) is still recruiting and builds on GRECCAR2 comparing neoadjuvant FOLFIRINOX followed by CRT to CRT alone [76, 77]. In both arms, good responders will have local excision of the primary to avoid major surgery. Similarly, the Chinese TNTCRT trial is designed to assess whether induction and consolidation CAPOX, nCRT, and TME improves DFS compared with standard nCRT and TME with adjuvant chemotherapy (NCT03177382). Circulating tumor DNA (ctDNA) is under investigation to guide adjuvant chemotherapy in stage II colon cancer [78, 79]. The DESTINY‐CRC01 trial proved that a drug–antibody conjugate (trastuzumab deruxtecan to target the HER2 receptor) is active against metastatic colon cancer that appropriately express the molecular target [80]. A deeper understanding of radiobiology may lead to molecularly targeted radio‐sensitizing agents [81, 82]. It may become possible to use immunotherapy in MSS LARC.
Summary Box
Early delivery of high-dose systemic chemotherapy represents a promising treatment strategy for both LARC and LRRC.
Favorable short-term outcomes include improved chemotherapy compliance and superior pathological response.
Long-term survival data are limited and interpretation is hampered by marked heterogeneity among neoadjuvant/adjuvant treatment regimes.
Prospective randomized trials will determine whether this approach can improve distant disease control and quality of life, and increase the proportion of patients suitable for non-operative management.
With increasing emphasis on personalized care, the future of rectal cancer management should include risk-adapted strategies incorporating the biomolecular and radiological profile of the tumor.
References
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