Purpose There are no randomized trials to guide treatment decisions between radiotherapeutic and surgical options for patients with high-risk localized prostate cancer. Comparative studies have been ...limited by their ability to match patients on the basis of pretreatment prognostic variables and to adjust for the cancer-related, medical, and socioeconomic differences between patients who choose radiotherapeutic or surgical approaches. Methods We analyzed the outcome of all patients in the National Cancer Database with high-risk, clinically localized prostate cancer with complete prognostic data who were treated with either radical prostatectomy (RP), external beam radiotherapy (EBRT) combined with androgen deprivation (AD), or EBRT plus brachytherapy with or without AD. Inverse probability of treatment weighting was used to adjust for covariable imbalance among treatment groups. The weighted time-dependent Cox proportional hazards model was then used to estimate the effects of treatment groups on survival, accounting for differential treatment initiation times. A predictive model of pathologic nodal (pLN) status was built using prostate-specific antigen level, Gleason score, and clinical T stage; predicted pLN status was used to repeat the inverse probability of treatment weighting and time-dependent Cox proportional hazards model. Results A total of 42,765 patients were analyzed. There was no statistically significant difference in survival between RP and EBRT plus brachytherapy with or without AD (hazard ratio HR, 1.17; 95% CI, 0.88 to 1.55). However, EBRT plus AD was associated with higher mortality than RP (HR, 1.53; 95% CI, 1.22 to 1.92). Adjustment for predicted pLN status did not yield statistically different results. A sensitivity analysis showed that EBRT plus AD ≥ 7920 cGy narrowed the difference, but a significantly higher mortality remained (HR, 1.33; 95% CI, 1.05 to 1.68). Conclusion After comprehensively adjusting for imbalances in prostate cancer prognostic factors, other medical conditions, and socioeconomic factors, this analysis showed no statistical difference in survival between patients treated with RP versus EBRT plus brachytherapy with or without AD. EBRT plus AD was associated with lower survival.
When drawing causal inferences about the effects of multiple treatments on clustered survival outcomes using observational data, we need to address implications of the multilevel data structure, ...multiple treatments, censoring, and unmeasured confounding for causal analyses. Few off‐the‐shelf causal inference tools are available to simultaneously tackle these issues. We develop a flexible random‐intercept accelerated failure time model, in which we use Bayesian additive regression trees to capture arbitrarily complex relationships between censored survival times and pre‐treatment covariates and use the random intercepts to capture cluster‐specific main effects. We develop an efficient Markov chain Monte Carlo algorithm to draw posterior inferences about the population survival effects of multiple treatments and examine the variability in cluster‐level effects. We further propose an interpretable sensitivity analysis approach to evaluate the sensitivity of drawn causal inferences about treatment effect to the potential magnitude of departure from the causal assumption of no unmeasured confounding. Expansive simulations empirically validate and demonstrate good practical operating characteristics of our proposed methods. Applying the proposed methods to a dataset on older high‐risk localized prostate cancer patients drawn from the National Cancer Database, we evaluate the comparative effects of three treatment approaches on patient survival, and assess the ramifications of potential unmeasured confounding. The methods developed in this work are readily available in the R$$ \mathsf{R}\kern.15em $$package riAFTBART$$ \mathsf{riAFTBART} $$.
Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized ...that atlas-based segmentation ("autocontouring") would lead to time savings and more consistent contours among physicians.
A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical target volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient.
For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean±standard deviation of 32±9 vs. 23±7 minutes, respectively (p=.000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30±3 vs. 21±5 min (p=.003), 39±12 vs. 30±5 min (p=.055), and 29±5 vs. 20±5 min (p=.0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p=.038).
The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the target volume.
Purpose of Review
The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease ...includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer.
Recent Findings
Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer.
Summary
Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.
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