Background
Phase III RCT (Stockholm III). 840 patients with resectable rectal cancer at 10 Swedish hospitals. Three-arm trial: short-course RT (SCRT) with short interval (≤1 week) to surgery, SCRT with long interval (4–8 weeks) to surgery, or long-course RT (LCRT: 50 Gy, no concurrent chemotherapy) with long interval. Primary endpoint: postoperative complications.
Interventions and follow up
Arm A: SCRT 25 Gy/5 fx → TME within 1 week
Arm B: SCRT 25 Gy/5 fx → TME at 4–8 weeks (delayed)
Arm C: LCRT 50 Gy/25 fx → TME at 4–8 week
Primary endpoint: Postoperative complicatio
mFollow up: Median 5.6 years (Erlandsson 2017); further outcomes Erlandsson 2019
Arm B: SCRT 25 Gy/5 fx → TME at 4–8 weeks (delayed)
Arm C: LCRT 50 Gy/25 fx → TME at 4–8 week
Primary endpoint: Postoperative complicatio
mFollow up: Median 5.6 years (Erlandsson 2017); further outcomes Erlandsson 2019
Results
Postoperative complications: SCRT/delayed 43% vs SCRT/immediate 53% vs LCRT 47% — delayed significantly fewer vs immediate (P=.001)
pCR: 12% (SCRT/delayed) vs 2% (SCRT/immediate) vs 4% (LCRT/long), P<.001
R0 resection: Similar across arms
Local recurrence at 5 yr: ~10% all arms, no significant difference
OS: No significant difference across arms
pCR: 12% (SCRT/delayed) vs 2% (SCRT/immediate) vs 4% (LCRT/long), P<.001
R0 resection: Similar across arms
Local recurrence at 5 yr: ~10% all arms, no significant difference
OS: No significant difference across arms
Adverse events
Main adverse events: SCRT with delayed surgery: lower postoperative complication rates vs immediate surgery. LCRT: higher late toxicity vs SCRT. Grade ≥3 acute toxicity higher with LCRT.
Conclusions
Short-course RT with a delayed interval to surgery (4–8 weeks) achieves significantly fewer postoperative complications than SCRT with immediate surgery and is equivalent to long-course RT in oncologic outcomes. SCRT with delay also achieved higher pCR rates (12%) than SCRT with immediate surgery (2%), providing downstaging opportunity. This has been pivotal in establishing SCRT + delay as an alternative to LCCRT.
Key Limitations
Key Limitations: LCRT (50 Gy) in Arm C had no concurrent chemotherapy — not the modern standard (which uses 5-FU or capecitabine concurrent CRT). Primary endpoint of postoperative complications may not translate to long-term oncologic benefit. Three-arm design with unequal allocation reduced power for pairwise OS comparisons. No adjuvant chemotherapy was mandated.
Clinical Context
Stockholm III validated SCRT with delayed surgery (4–8 weeks) as equivalent to LCCRT in oncologic outcomes with less acute toxicity. The higher pCR with SCRT + delay (12%) supports this approach for patients who cannot tolerate concurrent chemotherapy. RAPIDO subsequently used SCRT with 18 weeks of interval CAPOX before surgery, achieving ~28% pCR and demonstrating disease-related treatment failure benefit.