PSA After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and EBRT

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•The aim of this study was to evaluate whether PSA levels after "neoadjuvant" androgen deprivation therapy (ADT) with external beam radiation (EBRT) are associated with clinical outcomes. Patients were divided into two groups, including PSA levels >0.1 ng/mL and ≤0.1 ng/mL following ADT with EBRT. Median follow-up was 9.4 years, with over 2400 patients included in the analysis. At 5 years, the incidence of biochemical failure for patients post neoadjuvant ADT with PSA levels ≤0.1 ng/mL was 12%, whereas it was 27% for those with PSA levels >0.1 ng/mL. Overall survival was 88% versus 85% for those with PSA ≤0.1 ng/mL versus >0.1 ng/mL, respectively.

•PSA after ADT is associated with biochemical and clinical outcomes, and, with further evidence, could be considered an indicator of risk of recurrence following ADT with EBRT.

– Amy Luckenbaugh, MD

Advanced Prostate Cancer 

Written by Brian E Lewis MD, MPH, FACP

This was a pooled analysis from four trials, NRG Oncology/RTOG 9202, 9408, 9413, and 9910, which evaluated the role of ADT with radiation for definitive treatment of prostate cancer. These four trials evaluated the role of different durations of androgen suppression in combination with radiation therapy. The investigators of this paper evaluated the pooled patient population from these four trials who received neoadjuvant androgen suppression. The endpoint was the ability of the PSA to act as a prognostic marker prior to the initiation of radiation therapy and after 2 months of androgen suppression. They found that the lower the PSA level attained prior to the initiation of radiation therapy, the better the patient did with regard to biochemical failure, development of distant metastasis, overall survival, and cause-specific mortality. In particular, if the PSA after 2 months of ADT and prior to radiation was ≤0.1 ng/mL, the patients had better outcomes in the above categories.

This was a large analysis of 2404 patients in the final cohort. This wasn’t the initial endpoint of any of the trials involved in this analysis, which needs to be considered. It’s also not terribly unexpected that patients who achieve a lower PSA have a tendency to do better with regard to disease control. How this is going impact decision making with regard to longer therapy or additional therapy isn’t clear, and given that it is a pooled retrospective analysis, I don’t think this is going to change practice very much. However, I do think that this paper can help provide some prognostic information for patients and their physicians with regard to expectations.

PURPOSE

To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer.

METHODS AND MATERIALS

This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs >0.1 ng/mL) groupings, and clinical outcomes.

RESULTS

The median follow-up for surviving patients was 9.4 years. The median post-neoAS, pre-RT PSA level was 0.3 ng/mL, with 32% of patients having levels ≤0.1 ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and >0.1 ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1 ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P < .0001); local failure (HR, 2.51; P < .0001); distant metastases (HR, 1.73; P = .0006); cause-specific mortality (HR, 2.36; P < .0001); and all-cause mortality (HR, 1.24; P = .005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1 ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P < .0001); local failure (HR, 2.33; P < .0001); and cause-specific mortality (HR, 1.75; P = .03).

CONCLUSIONS

Patients with a PSA level >0.1 ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1 ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

International Journal of Radiation Oncology*Biology*Physics

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials

Int. J. Radiat. Oncol. Biol. Phys 2019 Aug 01;104(5)1057-1065, CL Hallemeier, P Zhang, TM Pisansky, GE Hanks, DG McGowan, M Roach, KL Zeitzer, SY Firat, SM Husain, DP D'Souza, L Souhami, MB Parliament, SA Rosenthal, HR Lukka, M Rotman, EM Horwitz, EF Miles, R Paulus, HM Sandler

[timotur]

I saw this study last week before talking to my Oncology guy and mentioned it to him. He said when PSA reaches <0.1 on neo-adjunctive ADT before radiation, it's a good sign that the PCa is still hormone-sensitive and is more sensitive to radiation treatment. He also said, if prior radiation was done before the IMRT, such as HDR-BT, and reached <0.1 it's another indication that the PCa was probably in the HDR radiation field. He said there's a ongoing study at UCSD showing that the chances of BCR increase at a level of 0.6 going into external radiation.