Comparative Outcomes of Neo-Adjuvant Chemo-Radiotherapy in Stage II and III Mucinous versus Non-Mucinous Rectal Adenocarcinoma: A Retrospective Study

Waheeb Radman Al-Kubati1– 3 1Surgery Department, 21 September University, Sana’a, Yemen; 2Physiology Department, Sana’a University, Sana’a, Yemen; 3Surgery Department Althowra Modern General Hospital, Sana’a, YemenCorrespondence: Waheeb Radman Al-Kubati, Surgery Department, 21 September University, Sana’a, Yemen, Email [email protected]: This study investigates the effectiveness of neo-adjuvant chemo-radiotherapy (neo-CRT) in patients with clinical stage II and III mucinous rectal adenocarcinoma (MRA) and compares clinical outcomes with those of non-mucinous rectal adenocarcinoma (NMRA).Methods: A retrospective analysis was performed on patients diagnosed with clinical stage II or III rectal adenocarcinoma, confirmed via pelvic imaging, who underwent curative surgical procedures from January 2009 to December 2023. Exclusion criteria encompassed stage I and IV cases, those treated as emergencies, and patients with inflammatory bowel disease. Patients were classified into neo-adjuvant treatment groups and compared based on tumor type (MRA vs NMRA) using statistical analyses.Results: Of 550 cases, 359 met inclusion. Most patients were young adults (58% aged 20– 30), reflecting unusually early onset in Yemen. Neo-CRT was administered to 180 patients (93 MRA, 87 NMRA), while 179 (87 MRA, 92 NMRA) did not receive it. NMRA tumors were 3.24× more likely to downstage than MRA (P = 0.0007; OR = 3.235). After CRT, yp Stage II occurred in 40.23% of NMRA (95% CI: 30.68– 50.68%) versus 17% of MRA (95% CI: 10.99– 26.15%), while yp Stage III persisted in 60% versus 82.80% respectively (P = 0.0003). Pathological complete response (pCR) was seen in 11% of NMRA but < 2% of MRA. Survival analysis showed MRA as the strongest adverse factor (CSS HR = 2.07, 95% CI: 1.39– 3.09, P = 0.0002; OS HR = 1.79, 95% CI: 1.25– 2.57, P = 0.0013), with advanced stage also predictive of poorer outcomes (CSS HR = 1.65, P = 0.043; OS HR = 1.87, P = 0.006). Neo-CRT itself conferred no survival benefit (CSS HR = 0.98, P = 0.91; OS HR = 1.24, P = 0.24). Disease-free survival (DFS) was lower in MRA (52% vs 72%, P = 0.004) and local recurrence higher (26% vs 5%, P = 0.0004), while Neo-CRT produced no significant survival benefit (15% vs 19%, P = 0.40).Conclusion: Both MRA stages II and III showed inferior cancer-free and overall survival outcomes. The justification for neo-adjuvant therapy necessitates a careful evaluation of potential benefits versus risks in MRA patients. The younger age of Yemeni colorectal cancer patients warrants further epidemiological studies to explore genetic and environmental risk factors. It also highlights the urgent need for tailored screening protocols, public health interventions, and awareness campaigns.Plain Language Summary: This study looked at how effective chemo-radiotherapy (given before surgery) is for patients with mucinous rectal cancer (MRA) compared to non-mucinous rectal cancer (NMRA) in stage II and III. Researchers reviewed records from 2009 to 2023. Out of 550 cases, 359 met the criteria. Among them, 180 received chemo-radiotherapy before surgery (39 MRA, 90 NMRA), and 179 did not (87 MRA and 92 NMRA) mainly due to health issues.Patients with NMRA showed better tumor shrinkage and lower cancer stage after treatment. They also lived longer and had fewer recurrences than MRA patients. In those who did not get chemo-radiotherapy, outcomes were similar between MRA and NMRA.In summary, MRA responded less to pre-surgery treatment and had worse survival. This calls for careful use of chemo-radiotherapy in MRA and highlights the need for early screening and awareness, especially since Yemeni patients are often younger.Keywords: neo-adjuvant chemo-radiotherapy, mucinous rectal adenocarcinoma, MRA, non-mucinous rectal adenocarcinoma, NMRA, cancer-specific survival, CSS, overall survival, OS