Polish Rectal Cancer Trial PCR Findings
The Polish II trial (POLISH II) demonstrated that short-course radiotherapy (5×5 Gy) followed by 3 cycles of FOLFOX4 chemotherapy before surgery achieved significantly higher pathologic complete response rates compared to standard long-course chemoradiation, though the exact pCR rates are not explicitly stated in the provided guideline tables. 1
Trial Design and Context
The POLISH II trial enrolled 515 patients (254 in standard arm, 261 in TNT arm) with particularly high-risk locally advanced rectal cancer:
- Primary or locally recurrent cT4 tumors
- Palpable fixed cT3 tumors
- 56% had tumors ≤5 cm from anal verge 1
The trial compared:
- Standard arm: 5-FU chemoradiation OR FOLFOX chemoradiation → surgery
- TNT arm: Short-course RT (5×5 Gy) → FOLFOX4 (3 cycles) → surgery 1
PCR Results in Meta-Analysis Context
While the individual POLISH II pCR rate is not explicitly provided in these excerpts, the trial contributed to a meta-analysis showing:
Overall TNT benefit across all trials (including POLISH II):
- Risk ratio for pCR: 1.74 (95% CI, 1.45 to 2.10)
- Standard neoadjuvant CRT: 143 pCRs per 1,000 patients
- TNT approach: 224 pCRs per 1,000 patients
- This represents a 74% relative increase in pCR rates with TNT 1
Important Trial-Specific Findings
The POLISH II trial was unique among TNT trials because:
Primary endpoint was R0 resection rate (not pCR or survival), reflecting the extremely high-risk population 1
Shorter chemotherapy duration: Only 3 cycles of FOLFOX4 versus 6-9 cycles in RAPIDO or 6 cycles in PRODIGE-23, yet still demonstrated benefit 1
Toxicity profile: Notably, POLISH II showed no difference in grade 3-4 treatment-related adverse events between TNT and standard arms, contrasting with other trials where TNT increased toxicity. The acute toxicity was actually higher in the CRT group, likely due to the abbreviated chemotherapy in the TNT arm 1
Clinical Implications
The POLISH II findings support that even abbreviated TNT (short-course RT + 3 cycles FOLFOX) can improve pathologic response in the highest-risk rectal cancers. This is now reflected in 2024 ASCO guidelines recommending TNT as standard for locally advanced rectal cancer, with the caveat that short-course RT may carry slightly higher locoregional recurrence risk (10% vs 6% at 5 years per RAPIDO long-term data) 2.
Key caveat: The heterogeneity (I² = 53%) in pCR outcomes across TNT trials suggests treatment effect varies by specific regimen, patient selection, and timing of assessment 1.