Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy.

OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.

Rectal Cancer after Prostate Radiation: A Complex and Controversial Disease.

A small proportion of rectal adenocarcinomas develop in patients many years after the treatment of a previous cancer using pelvic radiation, and the incidence of these rectal cancers depends on the length of follow-up from the end of radiotherapy. The risk of radiation-associated rectal cancer (RARC) is higher in patients treated with prostate external beam radiotherapy than it is in patients treated with brachytherapy. The molecular features of RARC have not been fully investigated, and survival is lower compared to non-irradiated rectal cancer patients. Ultimately, it is unclear whether the worse outcomes are related to differences in patient characteristics, treatment-related factors, or tumor biology. Radiation is widely used in the management of rectal adenocarcinoma; however, pelvic re-irradiation of RARC is challenging and carries a higher risk of treatment complications. Although RARC can develop in patients treated for a variety of malignancies, it is most common in patients treated for prostate cancer. This study will review the incidence, molecular characteristics, clinical course, and treatment outcomes of rectal adenocarcinoma in patients previously treated with radiation for prostate cancer. For clarity, we will distinguish between rectal cancer not associated with prostate cancer (RCNAPC), rectal cancer in non-irradiated prostate cancer patients (RCNRPC), and rectal cancer in irradiated prostate cancer patients (RCRPC). RARC represents a unique but understudied subset of rectal cancer, and thus requires a more comprehensive investigation in order to improve its treatment and prognosis.