Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials, ASCO/ Journal of Clinical Oncology, Newest Content, Oct 2022.
Maybe some non-specific validation of the ADT to RT timing issue related in this earlier FPC post by mateobeach?:
Testosterone “Flare” (Or Testosterone?) Timing to Optimize Salvage Radiation Therapy
The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).
MATERIALS AND METHODS\
Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality.
RESULTS
Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.
CONCLUSION
ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.
And the link to the full paper:
Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials, ASCO/ Journal of Clinical Oncology, Newest Content, Oct 2022.
But ultimately, YOU were the source for me... All roads lead back to the K9 Terror.... Interesting that we have been discussing this approach for 6 months, and other places...
Pablo showed superior planning over me on his approach by adding Lu-J591. Live and learn... Concurrent/ adjuvant should be the standard for IADT. OMHSPCa guys....Pay attention !!! ... sequence your tx ... get the best bang for the buck... and remember... you heard it through the K9 ... and a few others...
The Science is Coming !!!! and you can find it....HERE !!!!
A question that I ponder is how the sequencing effects the abscopal response. Does the sequencing do more than just enhance killing PCa cells, and provide a "boost" by prolonging the abscopal effect?? I have looked a bit and can not find any evidence for or against the possibility.
Radiotherapy-Related Gene Signature in Prostate Cancer
Abstract
Radiotherapy for localized prostate cancer has increased the cure and survival rates of patients. Besides its local tumoricidal effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation, a phenomenon called the abscopal effect. In this study, we performed gene expression analysis on peripheral blood from prostate cancer patients obtained post- radiotherapy and showed that 6 genes, including CCR7, FCGR2B, BTLA, CD6, CD3D, and CD3E, were down-regulated by a range of 1.5-2.5-fold as compared to pre-radiotherapy samples. The expression of the signature consisting of these six genes was also significantly lower post- vs. pre-radiotherapy. These genes are involved in various tumor-promoting immune pathways and their down-regulation post-radiotherapy could be considered beneficial for patients. This is supported by the fact that low mRNA expression levels for the 6-gene signature in the prostate tumor tissue was linked to better survival. Importantly, we report that this 6-gene signature strongly correlated with a favorable prognosis regardless of poor standard clinicopathological parameters (i.e., Gleason score ≥ 8 and T3 (including T3a and T3b). Our pioneering data open the possibility that the 6-gene signature identified herein may have a predictive value, but this requires further long-term studies.
The 6 gene monitoring would be good for a pre and post test indicator of success or no success. During ORIOLE trial, they monitored wbc's under a microscope post tx, to see if they were activated against PCa and for how long. Some individuals showed activated wbc's for over 3 months. The basis of the abscopal effect. That is my question, " Does sequencing ADT with SBRT enhance the abscopal effect??". While there is no proof today, I believe it may be the source for why individuals treated with sequencing had longer MFS because the sequencing tx enhanced the abscopal effect. Speculation.
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