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{{info | |||
| title= Organ Preservation for Rectal Adenocarcinoma | |||
| abbreviation= OPRA | |||
| expansion= Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy | |||
| published= 2022-04-28 | |||
| author= Garcia-Aguilar J, et al. | |||
| journal= Journal of Clinical Oncology | |||
| year= 2022 | |||
| volume= 40 | |||
| issue= 23 | |||
| pages= 2546-2556 | |||
| pmid= 35477112 | |||
| fulltexturl= https://ascopubs.org/doi/full/10.1200/JCO.22.00032 | |||
| pdfurl= https://ascopubs.org/doi/pdf/10.1200/JCO.22.00032 | |||
| status= | |||
| statusUsableDate= | |||
| subspecialty= | |||
| otherSubspecialty1= | |||
| disease= Rectal Cancer | |||
| intervention1= Total Neoadjuvant Therapy with Induction Chemotherapy | |||
| intervention2= Total Neoadjuvant Therapy with Consolidation Chemotherapy | |||
| briefDesignDescription= Randomized trial comparing disease-free survival and organ preservation with two neoadjuvant therapy sequences in rectal cancer | |||
| briefResultsDescription= Organ preservation achieved in ~50% of patients with no detriment to disease-free survival | |||
| trainingLevel= | |||
}} | |||
==Clinical Question== | |||
Can total neoadjuvant therapy (TNT) and a selective watch-and-wait (WW) approach achieve comparable disease-free survival (DFS) to standard therapy, and does the sequence of TNT affect outcomes? | |||
==Bottom Line== | |||
Organ preservation was achieved in nearly half of patients with locally advanced rectal adenocarcinoma using TNT and a selective WW approach without compromising DFS. Delivering chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) led to higher organ preservation rates than induction chemotherapy followed by chemoradiotherapy (INCT-CRT). | |||
==Major Points== | |||
* The OPRA trial evaluated the efficacy of organ preservation in rectal cancer using TNT and selective WW or total mesorectal excision (TME) based on tumor response. | |||
* 324 patients with stage II-III rectal adenocarcinoma were randomized to INCT-CRT or CRT-CNCT and treated with TNT (systemic chemotherapy and chemoradiotherapy). | |||
* Patients were restaged after TNT; those with a complete or near-complete clinical response were managed with WW, while others underwent TME. | |||
* Primary endpoint: 3-year DFS. Secondary endpoints: TME-free survival, local recurrence-free survival, and distant metastasis-free survival. | |||
* At 3 years, DFS was 76% in both INCT-CRT and CRT-CNCT groups, comparable to historical controls. | |||
* Organ preservation rates were 41% for INCT-CRT and 53% for CRT-CNCT (p=0.01). | |||
==Guidelines== | |||
'''NCCN Rectal Cancer Guidelines''' (Version 6.2020, adapted)<ref>{{#pmid:32634877}}</ref> | |||
* TNT with selective WW is an option for patients achieving a complete clinical response (cCR). | |||
* Organ preservation strategies require rigorous surveillance to monitor for regrowth or recurrence. | |||
==Design== | |||
* Phase II, randomized, multicenter trial | |||
* N=324 patients with stage II or III rectal adenocarcinoma | |||
* Setting: 18 institutions in the United States | |||
* Enrollment: 2014-2020 | |||
* Follow-up: Median 3 years | |||
* Primary endpoint: 3-year DFS | |||
* Secondary endpoints: TME-free survival, adverse events, and local/distant recurrence rates | |||
* Analysis: Intention-to-treat, Kaplan-Meier survival estimates, and multivariable Cox regression | |||
==Population== | |||
===Inclusion Criteria=== | |||
* Age >18 years | |||
* Stage II (T3-4, N0) or III (any T, N1-2) rectal adenocarcinoma | |||
* No distant metastasis or prior pelvic irradiation | |||
* Adequate organ function and ECOG performance status ≤1 | |||
===Exclusion Criteria=== | |||
* Recurrent rectal cancer | |||
* Incomplete staging or prior treatments disrupting TNT protocols | |||
* History of other malignancies within 5 years | |||
===Baseline Characteristics=== | |||
* Median age: 59 years | |||
* Clinical T stage: T3 (78%), T4 (13%) | |||
* Clinical nodal status: N-positive (71%) | |||
==Interventions== | |||
* **INCT-CRT group**: Induction chemotherapy (mFOLFOX6 or CAPEOX) followed by chemoradiotherapy | |||
* **CRT-CNCT group**: Chemoradiotherapy followed by consolidation chemotherapy (mFOLFOX6 or CAPEOX) | |||
* Radiotherapy: 4,500-5,600 cGy with concurrent capecitabine or infusional fluorouracil | |||
* Restaging with MRI, endoscopy, and physical exam to assess response | |||
==Outcomes== | |||
===Primary Outcome=== | |||
* 3-year DFS: 76% (both groups, p=NS) | |||
===Secondary Outcomes=== | |||
* Organ preservation (TME-free survival): 41% (INCT-CRT) vs. 53% (CRT-CNCT), p=0.01 | |||
* Local recurrence-free survival: 94% (both groups) | |||
* Distant metastasis-free survival: 84% (INCT-CRT) vs. 82% (CRT-CNCT) | |||
===Adverse Events=== | |||
* Grade ≥3 adverse events during TNT: 41% (INCT-CRT) vs. 34% (CRT-CNCT) | |||
==Criticisms== | |||
* Lack of a control arm with standard CRT and TME limits direct comparison to standard therapy. | |||
* Follow-up duration may be insufficient to assess long-term oncologic outcomes. | |||
* Higher organ preservation rate with CRT-CNCT may reflect differences in regrowth, not initial response rates. | |||
==Funding== | |||
* Supported by grants from the National Cancer Institute (R01CA182551, P30CA008748) | |||
==Further Reading== | |||
<references/> | |||