A Comparison of the Prognostic Value of Early PSA Test-Based Variables Following External Beam Radiotherapy, With or Without Preceding Androgen Deprivation: Analysis of Data From the TROG 96.01 Randomized Trial

Lamb, David; Denham, James W.; Joseph, David; Matthews, John; Atkinson, Callum; Spry, Nigel; Duchesne, Gillian; Ebert, Martin; Steigler, Allison; Delahunt, Brett; DʼEste, Catherine

doi:10.1016/j.ijrobp.2009.10.071

Cited by 36 publications

(20 citation statements)

References 22 publications

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“…Analysis of men in that study showed that pre-radiation PSA nadir of ≤ 0.3 ng/mL was associated with improved long-term biochemical tumor control (hazard ratio = 0.546, p < 0.001), reduction in distant metastases (hazard ratio = 0.62, p=0.003), and prostate cancer-related death (hazard ratio =0.595, p=0.01). [28] Post-radiation PSA-nadir in men treated with LHRHa and radiation has also been demonstrated to be a strong prognostic indicator of post-treatment outcomes including prostate cancer-specific mortality [29,30]All compliant men in our study had a post-radiation nadir of 0.2 or less, and 19 men had undetectable nadirs. Although it is too early to determine whether post-radiation PSA-nadir can serve as a valid surrogate endpoint in patients receiving neoadjuvant/concurrent abiraterone, it is promising that among our group of intermediate and high-risk patients, only one patient (5%) has had biochemical relapse at a median follow-up of 21 months, and no patient who completed full intended course of therapy has had a biochemical relapse.…”

Section: Discussionmentioning

confidence: 81%

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

Cho

Mostaghel

Russell

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Purpose/Objectives Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation with definitive radiotherapy in men with locally advanced or high-grade disease. Addition of abiraterone to LHRH agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Materials/Methods A prospective, phase II study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at discretion of treating clinician. Prostate biopsies were obtained prior to start of therapy and prior to radiation. Serum and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results 22 men with intermediate (3) and high-risk PCa (19) received study therapy. 16 men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4–81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14),, fatigue (1), transaminitis (2), hypertension (2), and hypokalemia (1). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone had pre-radiation PSA nadir of <0.3. Median levels of tissue androgens downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range 3–37), only one patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising with excellent PSA nadir and no relapse to date in this high-risk population.

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Section: Discussionmentioning

confidence: 81%

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

Cho

Mostaghel

Russell

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…Consistent with dose escalation trials which have showed a lower PSA nadir with increased total dose [7], we could expect the SBRT regimen to produce a lower PSA nadir. Lamb et al [19] showed that the post-radiation nadir PSA is the strongest indicator. Zelefsky et al [20] demonstrated that nadir PSA values of ≤1.5 ng/mL at 2 years after radiation therapy for prostate cancer predict for long-term distant metastases and cause-specific mortality.…”

Section: Discussionmentioning

confidence: 99%

Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma

2016

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PurposeStereotactic body radiotherapy (SBRT) takes advantage of low α/β ratio of prostate cancer to deliver a large dose in few fractions. We examined clinical outcomes of SBRT using CyberKnife for the treatment of low- and intermediate-risk prostate cancer.Materials and MethodsThis study was based on a retrospective analysis of the 33 patients treated with SBRT using CyberKnife for localized prostate cancer (27.3% in low-risk and 72.7% in intermediate-risk). Total dose of 36.25 Gy in 5 fractions of 7.25 Gy were administered. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored.ResultsThirty-three patients with a median 51 months (range, 6 to 71 months) follow-up were analyzed. There was no biochemical failure. Median PSA nadir was 0.27 ng/mL at median 33 months and PSA bounce occurred in 30.3% (n = 10) of patients at median at median 10.5 months after SBRT. No grade 3 acute toxicity was noted. The 18.2% of the patients had acute grade 2 genitourinary (GU) toxicities and 21.2% had acute grade 2 gastrointestinal (GI) toxicities. After follow-up of 2 months, most complications had returned to baseline. There was no grade 3 late GU and GI toxicity.ConclusionOur experience with SBRT using CyberKnife in low- and intermediate-risk prostate cancer demonstrates favorable efficacy and toxicity. Further studies with more patients and longer follow-up duration are required.

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“…This longer TnPSA is also contrary to Kitagawa et al (28) who note that if there is a relationship between TnPSA and hormones, an early TnPSA is advantageous when hormones are used in isolation. Nevertheless, caution must be applied when considering nPSA and TnPSA as surrogate endpoints owing to possible dependence treatment variables such as hormone use (3). Furthermore, large-scale prospective studies are needed to further explore the correlation between PSA kinetics and long-term outcomes after brachytherapy either with or without hormone treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, there is little consensus in the literature on a threshold absolute nPSA value that can predict long-term control, with absolute nPSA values varying depending on the radiation technique used and the dose delivered (3). Pretreatment factors such as iPSA, Gleason score category, and T-stage may also influence the nPSA value (3).…”

Section: Discussionmentioning

confidence: 99%

Does prostate-specific antigen nadir predict longer-term outcomes of prostate cancer after neoadjuvant and adjuvant androgen deprivation therapy in conjunction with brachytherapy?

2015

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A Comparison of the Prognostic Value of Early PSA Test-Based Variables Following External Beam Radiotherapy, With or Without Preceding Androgen Deprivation: Analysis of Data From the TROG 96.01 Randomized Trial

Cited by 36 publications

References 22 publications

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma

Does prostate-specific antigen nadir predict longer-term outcomes of prostate cancer after neoadjuvant and adjuvant androgen deprivation therapy in conjunction with brachytherapy?

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