Low PSA on ADT: Still Prognostic in New Treatment Era

Nick Mulcahy

January 23, 2018

A low prostate-specific antigen (PSA) value continues to be a helpful prognostic marker in the setting of hormone-sensitive metastatic prostate cancer, even as standard treatment evolves.

The finding comes from a retrospective analysis published online December 20, 2017, in the Journal of Clinical Oncology.

Among oncologists and urologists, it is well known that a PSA level of 0.2 ng/mL or less in these men at 7 months after the initiation of androgen deprivation therapy (ADT) portends a significantly longer survival than seen in men with PSA values above this cutoff point.

But that insight comes from a study published more than 10 years ago, the Southwest Oncology Group 9346 trial (J Clin Oncol. 2006;24:3984-3990). 

At that time, ADT alone was the mainstay of treatment. But times and treatments change.

Now, thanks to findings from the more recent CHAARTED and STAMPEDE trials, many of these patients receive chemotherapy with docetaxel in addition to ADT, especially if they have high-volume metastatic disease. Both of these major trials showed significantly improved overall survival when chemotherapy was added to androgen blockade in advanced prostate cancer.

But it has not been known, in the current treatment era, whether the PSA biomarker remained prognostic when docetaxel was added to ADT.

So the CHAARTED investigators performed a retrospective "landmark survival analysis" at 7 months using the database from their trial.

They conclude that  "PSA ≤ 0.2 ng/dL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration."

Finding Provides Optimism and Guidance

For clinicians, the new findings provide both "optimism at the bedside and perhaps also guidance on how close to follow patients," said investigators Lauren Harshman, MD, and Christopher Sweeney, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, in an email to Medscape Medical News.

The suggestion here is that for clinicians working with men whose PSA levels are below the cutpoint, there is positive news to share, while for men with PSA levels above that cutoff point, there is possible guidance for closer monitoring.

Study Details

In the study, 719 of the original 790 patients were eligible for the new subanalysis; 358 were treated with ADT plus docetaxel and 361 with ADT alone. The team used the three prognostic classifiers identified from the earlier SWOG 9346 trial: PSA level of 0.2 ng/dL or less,  greater than 0.2 to 4 ng/dL, and greater than 4 ng/dL.

The median follow-up was 23.1 months.

Across all patients, median overall survival was significantly longer if the 7-month PSA level reached  0.2 ng/dL or less vs survival seen with levels greater than 4 ng/dL (median survival, 60.4 months vs 22.2 months, respectively; P < .001).

On multivariable analysis, a 7-month PSA level of 0.2 ng/dL or less and low-volume disease were prognostic of longer overall survival (all P < .01).

Also, achieving a 7-month PSA level of 0.2 ng/dL or less was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSA levels (all P ≤ .01). 

The addition of docetaxel increased the likelihood of achieving a PSA level of 0.2 ng/dL or less at 7 months (45.3% vs 28.8% of patients receiving ADT alone). 

However, the patients who had the best median overall survival in the study (72.8 months) were those receiving ADT alone who achieved a 7-month PSA level of 0.2 ng/dL or less. (These men were also more likely to have low-volume disease, at 56.7%).

Dr Harshman and Dr Sweeney pointed out that the timing of receipt of docetaxel was variable in the study. Notably, they also observed that "getting  docetaxel around the time of ADT initiation increased the chances of achieving this good prognostic feature, and there was evidence patients may have been more likely to achieve this endpoint, the closer the docetaxel was given to the ADT start."

However, the pair cautioned clinicians not to make too much of the new findings in terms of making upfront treatment decisions.

"While intriguing, given the study's retrospective nature, clinicians should not make treatment decisions based on the PSA level at 7 months (eg, defer adding docetaxel based on the 7 month PSA level)," they said.

The Dana-Farber–based investigators also said that their results raise other questions about managing these patients.

"Our results are prompting many questions about whether these patients would benefit from therapy intensification prior to PSA or radiologic progression with the newer androgen-receptor targeted agents," they said. These newer agents include abiraterone acetate (Zytiga, Janssen) and enzalutamide (Xtandi, Astellas).

Sanofi provided docetaxel for use in CHAARTED. The National Cancer Institute Cancer Therapy Evaluation Program and the Eastern Cooperative Oncology Group (ECOG)–American College of Radiology Imaging Network (ACRIN) provided financial grant support. All study authors have financial ties to industry, including to Sanofi and other companies with drug treatments for prostate cancer.

J Clin Oncol. Published online December 20, 2017. Abstract

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