A single injection of androgen deprivation therapy (ADT) for men otherwise being managed with active surveillance for low-risk prostate cancer improves a number of short-term outcomes and may eradicate small malignancies, according to results from a novel phase 3 trial from France.
"ADT can probably be used to reverse low-risk prostate cancer lesions," study author Eva Comperat, MD, PhD, a pathologist at Sorbonne University in Paris, said here during a plenary session of the American Urological Association (AUA) 2018 annual meeting. "And it improves the results obtained with subsequent active surveillance."
However, an American expert who was approached for comment was unconvinced by the results. "The concept of administering androgen ablation for low-risk prostate cancer to otherwise healthy men is going to be extremely controversial, and to some, unpalatable," commented Alexander Kutikov, MD, of the Fox Chase Cancer Center in Philadephia, Pennsylvania.
Study Details
In the randomized trial, the researchers assigned men to receive either a one-time "transient" dose of ADT (effective for 3 months) plus active surveillance (n = 58) or active surveillance alone (n = 57).
The ADT was a single subcutaneous injection of leuprolide acetate 11.25 mg, a commonly used gonadotropin-releasing hormone agonist.
All of the men had low-risk disease, which was defined as disease of clinical stage T1c or T2a; a PSA level of ≤10 ng/mL; a Gleason score of ≤6; and, on 12-core staging biopsy, findings of at least one positive core, with no core indicating a tumor length >3 mm.
After her presentation, Comperat told Medscape Medical News that the rationale behind the trial is that substantial numbers of men with low-risk disease will experience disease progression on active surveillance and will need radical prostatectomy. As a possible solution, a brief chemical intervention with ADT may completely eradicate the tumor at an early point in time, she suggested.
The main endpoint of the study was a negative 12-core biopsy result at 12 months. The team reported that 53% of the patients in the ADT group met that endpoint; in the standard-care group, 32% of patients met that endpoint, a difference that was statistically significant (P = .03).
Comperat acknowledged that a negative biopsy is not proof of eradicated disease, but it is a good proxy, she commented.
In the study abstract, the study authors say that the biopsy results "suggest that ADT can be used to reverse low-risk prostate cancer lesions, hence improving the results obtained with subsequent active surveillance."
The treatment process may allow for the detection of hidden, aggressive disease; other research suggests that aggressiveness "can be assessed by response to early ADT," they write. Comperat explained that the lesions that remain after ADT may be more aggressive and resilient, given the fact that they were not vanquished by the ADT.
Better Quality of Life
The ADT also led to a better quality of life, say the French teamThe ADT group showed an improvement in International Prostate Symptoms Score at 9 months, as well as statistically significant reductions in PSA scores at 3 and 6 months, compared to the standard-surveillance group,
Another positive finding was that there was no statistically significant difference in erectile function at 12 months, as demonstrated on International Index of Erectile Function–5 score, between men in the ADT group and those in the standard-surveillance group.
Also, there was no difference between the study groups in tumor radiologic progression, as assessed by MRI.
The idea of treating low-risk disease with ADT will be not be highly popular, predicted Kutikov. He also pointed out that "many would argue that this no longer qualifies as active surveillance."
The current results are not compelling clinical evidence, he added: "The fact that there were more negative biopsies in the lueprorelin group and the fact that PSA levels dropped is less than exciting."
The authors will need to show that there is a drop in disease progression with the ADT treatment, said Kutikov.
In other words, the team will have to demonstrate on intermediate- and long-term follow-up that there was a decrease in Gleason grade disease and a reduction in related surgery/radiotherapy. "Until then, I personally will remain extremely skeptical about this approach," he told Medscape Medical News.
On the plus side, no serious adverse events related to the study drug were observed.
In their abstract, the study authors noted preliminary results of a pilot series from two French urology centers involving low-risk prostate cancer patients. For patients who received ADT and a 5-alpha-reductase inhibitor for 3 months, tumor regression occurred in about 60% of patients, suggesting that low-risk prostate cancer can be reversed by ADT. The new study intended to confirm these results on a larger scale, the study authors say.
The study was funded by Takeda, which makes leuprolide acetate for prostate cancer treatment. The study authors have disclosed no relevant financial relationships. Dr Kutikov reports financial ties to industry, but none relevant to the current research.
American Urological Association (AUA) 2018. Abstract LBA18, presented May 21.
Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick
For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου