Survival outcomes of metastatic renal cell carcinoma (mRCC) with sarcomatoid differentiation (SD): A single-institutional experience and literature meta-analysis.
Bibliographic record
Abstract
332 Background: Patients (pts) with mRCC with SD have unfavorable outcomes and poor prognosis due to aggressive tumor behavior. Chemotherapy and targeted treatment are often of little benefit. However, recent studies have shown a survival benefit of immunotherapy (IO). Here, we report survival outcomes of pts with mRCC with SD treated with first line IO or chemotherapy or targeted treatment. In addition we performed a meta-analysis of recent practice changing phase III, IO trials in mRCC. Methods: This retrospective survival analysis was performed in pts with mRCC with SD treated with IO or non-IO treatment at Princess Margaret Cancer Centre (PM), Toronto. Demographics, disease characteristics and survival outcomes were collected. Progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method (log-rank). PFS and OS hazard ratios (HR) were calculated using cox proportional hazards model. We identified the major, practice changing clinical trials that reported survival outcomes of mRCC with SD treated with IO and performed a random-effects meta-analysis of HR for PFS and OS. We compared these pooled results to our single institution experience. Results: We identified 474 pts diagnosed with mRCC at PM between 2002 and 2019. In total, 44 (9.3%) pts had mRCC with SD who were treated with IO or non-IO. Of these, 29 (65.9%) pts had pure SD and 15 (34.1%) pts had mixed rhabdoid and SD features. Median age was 59.6 years (36-78) and 33 (75%) were male. Overall, as per the IMDC score, 3(6.8%), 21(47.7%) and 20(45.5%) pts were categorized as good, intermediate, and poor risk, respectively. Eight (18.2%) pts were treated with IO as first line of treatment, and 36 (81.8%) pts received non-IO. With a median follow up of 64.8 months (range, 45.7-83.8 months), the median OS for the whole mRCC with SD cohort was 15.6 months (95% CI: 8.6-22.5). The median OS in all pts treated with IO vs non-IO was not reached vs 10.3 months (95%CI: 1.49-19.1 months; p = 0.005), respectively. The HR for OS was 0.1 (95%CI: 0.01-0.78; p = 0.023) favoring IO receipt. The median PFS in all pts treated with IO vs non-IO was 24 months (95%CI: non-estimable) vs 5.4 months (95%CI: 2.9-7.8 months; p = 0.021), respectively. The HR for PFS was 0.3 (95%CI: 0.11-0.89; p = 0.03) favoring IO receipt. We identified through meta-analysis five phase III clinical trials reporting PFS and OS in pts with mRCC with SD who received IO. The overall HR for OS and PFS for the total cohort were 0.55 (95%CI: 0.41-0.74), and 0.53 (95%CI: 0.42-0.67), respectively. Conclusions: Our meta-analysis has confirmed the benefit of IO agents in mRCC with SD. While the numbers included in this retrospective review were small, they have provided real world corroboration of the trial findings. Pts with mRCC and SD benefit from IO treatment, which should be considered the standard of care for these patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.024 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.028 |
| Bibliometrics | 0.005 | 0.006 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".