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Advanced Prostate Cancer

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searching for a specific study/aggressive approach

TheTopBanana profile image
5 Replies

hello, again. first of all thank you all very very very much for helping me and my father navigate through all of this. I can't imagine these last three months without this forum.

now to my question: me and my father talked to a Swedish doctor today who advised against an aggressive early approach with chemo (something that my father thinks he perhaps wants, suits his mentality) and the doctor said that there had been a big study on an aggressive approach for breast cancer which he used as an argument against early chemo. he couldn't remember the name of the study, something with 2000, does this ring a bell for anyone?

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Tall_Allen profile image
Tall_Allen

I don't know about breast cancer, but the Oudard RCT (discussed in the link below) supports what his Swedish oncologist says for prostate cancer. In that trial, none of the men had any metastases on a bone scan/CT but they very well might have been detectable on a PSMA PET if it had been used (as it was for your father). So, for men like your father who were recurrent but had no bone scan/CT-detectable metastases, they proved that docetaxel conferred no benefit.

prostatecancer.news/2019/02...

timotur profile image
timotur

There are several European studies on early use of docetaxel in different pathologies/stages. Bottom line is it only adds to O/S for high risk (GL > 8) and heavily burdened metastatic patients.

This from RTOG 1503...

Since NRG Oncology RTOG 0521 was designed, there have been other studies examining the role of docetaxel CT earlier in the clinical course of prostate cancer. GETUG-12 (Groupe d’Étude des Tumeurs Urogénitales)19 randomly assigned 413 patients with high-risk clinically localized disease treated with local therapy to AS (36 months) plus four cycles of adjuvant CT with docetaxel and estramustine or AS alone. Although the addition of CT increased relapse-free survival, a recent update of GETUG-12 demonstrated no statistically significant improvement in a prespecified end point of metastasis-free survival.20 In addition, the Scandinavian trial SPCG-13 (Scandinavian Prostate Cancer Group) demonstrated no benefit in biochemical DFS in a cohort of 378 men with intermediate- or high-risk disease randomly assigned to AS (12 months) plus adjuvant CT with six cycles of docetaxel CT versus AS alone.21 Similarly, the SPCG-12 study showed no benefit in biochemical DFS for 459 high-risk patients randomly assigned to radical prostatectomy plus adjuvant CT with six cycles of docetaxel chemotherapy versus radical prostatectomy alone.22 The discordance in results between RTOG 0521, which showed benefits in OS, DM, and DFS, and GETUG-12, SPCG-13, and SPCG-12 may stem from differences in patient populations among the studies. The RTOG 0521 cohort included patients with more aggressive disease; 84% of patients in RTOG 0521 had a Gleason score 8 to 10 disease, whereas a majority of patients in GETUG-12, SPCG-13, and SPCG-12 had a Gleason score less than or equal to 7 disease. These differences underscore the need to select high-risk patients with the most aggressive disease when considering treatment with adjuvant docetaxel.

CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) study,7 790 patients were randomly assigned to AS or AS + CT with six cycles of docetaxel. Median OS was improved with CT from 44 to 58 months. The survival benefit seemed to be restricted to those with higher-volume metastatic disease. In addition, the GETUG-15 study, with a smaller sample size than CHAARTED, did not show an OS benefit,23 although an update24 showed a trend toward OS benefit among the subset with high-volume disease as defined in CHAARTED. In the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial, which included patients with metastatic and nonmetastatic disease, docetaxel improved survival for men with castration-sensitive prostate cancer, with the primary benefit seen in patients with metastatic disease.8 Taken together, these studies suggest that there is a positive effect of docetaxel CT in subsets of men with castration-sensitive prostate cancer but reinforce the need for improved patient selection to better define these subsets. Studies in both nonmetastatic and metastatic castration-sensitive disease suggest a greater benefit of docetaxel in the subsets of patients with more aggressive disease features. In this study, PSA failure rates were not significantly different between the arms. It is possible that docetaxel, when used in combination with long-term AS + RT, may be focused on the androgen-insensitive clones that produce less PSA. This underlines the need for future investigation of the molecular profiles of patient samples from clinical trials to identify the biologic drivers of tumors in patients who benefit from docetaxel-based CT.

ascopubs.org/doi/full/10.12...

TheTopBanana profile image
TheTopBanana in reply to timotur

Thank you! My father is a Gleason 9, so he has the more aggressive cancer. Although few mets.

timotur profile image
timotur in reply to TheTopBanana

Ok, so RTOG 0521 is appropriate-- metastatic, HS, although not recurrent-- showed benefit, but GETUG-12 and the Swedish study, SPCG-13, did not.... Being in a lower-risk GL-7 group, I based my decision not to do early chemo on SPCG-13.

_______

RTOG 0521....

This phase III clinical trial was designed to test the hypothesis that docetaxel CT, known to improve OS for men with metastatic castration-sensitive prostate cancer, could improve OS among men with high-risk localized prostate cancer when used in an adjuvant fashion after standard RT and AS. An improvement in OS was observed with adjuvant CT in this setting. The CT was generally well tolerated. In addition, the cumulative incidence of DM was reduced, and there were improvements in DFS, although not DSS, using blinded central review of cause of death. The NRG Oncology RTOG 0521 study followed a previous adjuvant CT study, RTOG 9902, which was terminated early because of thromboembolic toxicity associated with estramustine.16,17 Lack of unanticipated toxicity and better-tolerated CT led to timely completion of this protocol.

RT doses were standard at the time of study accrual.18 Although the radiation doses in NRG Oncology RTOG 0521 (72 to 75.6 Gy) were modestly lower than contemporary RT doses (eg, 79.2 Gy), the hypothesized benefit of docetaxel was to be primarily in the reduction of DM. The study findings showed that the 6-year rate of DM was significantly lower at 9.1% in the AS + RT + CT arm versus 14.0% in the AS + RT arm (P = .044).

Since NRG Oncology RTOG 0521 was designed, there have been other studies examining the role of docetaxel CT earlier in the clinical course of prostate cancer. GETUG-12 (Groupe d’Étude des Tumeurs Urogénitales)19 randomly assigned 413 patients with high-risk clinically localized disease treated with local therapy to AS (36 months) plus four cycles of adjuvant CT with docetaxel and estramustine or AS alone. Although the addition of CT increased relapse-free survival, a recent update of GETUG-12 demonstrated no statistically significant improvement in a prespecified end point of metastasis-free survival.20 In addition, the Scandinavian trial SPCG-13 (Scandinavian Prostate Cancer Group) demonstrated no benefit in biochemical DFS in a cohort of 378 men with intermediate- or high-risk disease randomly assigned to AS (12 months) plus adjuvant CT with six cycles of docetaxel CT versus AS alone.21 Similarly, the SPCG-12 study showed no benefit in biochemical DFS for 459 high-risk patients

MateoBeach profile image
MateoBeach in reply to TheTopBanana

Reading along the above excellent information, it appears his G9 status gives support for the early use of docetaxel chemo if that is his inclination.

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