For all 29 LARC and LRRC patients from the phase 2 trial, follow-up data until August 3rd 2023 could be obtained, encompassing 12 LARC and 17 LRRC patients. Median follow-up until last oncologic assessment for patients that were alive at the time of analysis was 5.0 years (IQR 4.5–5.5). Baseline patient characteristics, tumor characteristics, local (re-)recurrence rates and survival outcomes are summarized in Table 1. Among LARC patients, the local recurrence rate was 25% (3/12), 58% (7/12) developed metastases and 33% (4/12) deceased related to the disease. One patient deceased 2 months after surgery due to a non-disease related cause. In the LRRC cohort, 65% of patients (11/17) were diagnosed with a local re-recurrence, 71% (12/17) developed metastases and 53% (9/12) deceased related to the disease.

Table 1 Demographics, pre/peri-operative characteristics, pathology and 5-year follow-up of 29 patients who underwent SGM-101 guided rectal cancer surgery from 2016–2018

Overall 5-year local (re-)recurrence-free survival was 35% (95% CI 4,8–65,2) for LARC patients and 24% (95% CI 3,3–43,7) for LRRC patients, while overall 5-year survival was 50% (95% CI 21,8–78,2) and 53% (95% CI 29,2–76,6) for LARC and LRRC respectively.

In 7/29 patients, there was a significant alteration in surgical plan due to NIRF (LARC n = 2 and LRRC n = 5). Follow-up results are shown below accordingly and are summarized in Fig. 3.

Fig. 3

follow-up results stratified based on significant alteration or no significant alteration using near-infrared fluorescence-guided surgery with SGM-101. For continues data with > 3 values the median is presented alongside the corresponding interquartile range (IQR) enclosed within brackets. For continuous data with only 3 values or less, the median is presented alongside the corresponding values enclosed within brackets

Follow-up Patients with Significant Alteration in Surgical PlanLARC (n = 2)

Of the two patients that had less invasive surgical treatment due to SGM-101, one patient, who did not undergo IORT on the sciatic nerve and turned out to have a pathological complete response, passed away two months after surgery due to an event unrelated to the disease. Consequently, no follow-up data could be obtained for this patient. The second patient, in which tissue around the lateral piriformis could be preserved with subsequently sparing of the internal iliac artery and vein (R0 at pathology), was locally recurrence-free at the last follow-up 63 months post-surgery. This patient was diagnosed with a colorectal lung metastasis 30 months after surgery which was curatively resected. See Fig. 3 for further details.

LRRC (n = 5)

Of the three patients that underwent an R0 resection instead of R1 due to NIRF-guided resection of additional malignant tissue, one patient (33%) developed a unifocal local re-recurrence in the pelvis five months after surgery. The other two patients (67%) did not develop a local re-recurrence until they deceased 31 and 32 months after surgery, respectively, due to disseminated disease. Their last oncological assessments were conducted at 24 and 31 months, respectively. The two patients with a NIRF-guided additional resection that still resulted in an R1 resection, developed a local re-recurrence at 4 and 23 months, respectively. Moreover, they developed distant metastases at 18 and 28 months and deceased 42 and 62 months after surgery, respectively. Additional details are summarized in Fig. 3.

Follow-up Patients Without Significant Alteration in Surgical PlanLARC (n = 10)

Eight patients had no alteration of the surgical plan and two patients had a minor, additional, false positive (fluorescent but benign) resection based on NIRF (all patients R0). Three patients (30%) developed a local recurrence (8, 11 and 45 months, respectively), five (50%) patients developed distant metastases after a median of 8 months (IQR: 7–32) and four patients (40%) deceased after a median of 47 months (IQR 28–58).

LRRC (n = 12)

In total 12 patients with LRRC had no significant alteration of the surgical plan (10/12 (83%) R0). In two of these patients a false positive (fluorescent but benign) additional resection was performed of remaining fluorescence in the wound bed. These resections were all minor in size and did not lead to post-operative morbidity higher than expected. Eight patients (67%) developed a local re-recurrence (R0 75%) after a median of 16 months (IQR: 8–34) and 7 patients (58%) developed distant metastases after a median of 8 months (IQR: 6–15), as shown in Fig. 3. Four patients (33%) deceased after a median of 34 months (IQR: 14–51).

Balance of Potential Drawbacks and Benefits SGM-101

Figure 4 illustrates the potential advantages and disadvantages of SGM-101. There were no reported adverse events or side effects related to the infusion of SGM-101. However, in five patients, false positive additional resections were performed (fluorescent but benign tissue). These resections were all minor in size and did not lead to post-operative morbidity higher than expected levels. One of the false positive NIRF-based minor additional resections occurred in patient 4 (Supplementary Table 1), in whom also two true positive (fluorescent and malignant tissue) additional resections were performed.

Fig. 4

Balancing the clinical disadvantages of the usage of SGM-101 (left side) and the potential advantages (right side)

Concerning the potential benefits of SGM-101: in five patients the imaging agent accurately identified additional true positive tissue, resulting in R0 resections in three patients, of whom two patients remained free from local (re-)recurrence in the follow-up. In two patients less invasive surgery was performed. One of these patients, with a pathological complete response, deceased non-disease related two months after surgery. The other patient did not develop a local recurrence and is still alive.