Androgen-deprivation therapy before radical surgery for prostate cancer may harm a subset of patients, help others, study suggests

A study from Japan suggests that men should probably avoid androgen blockade before prostate surgery if they are above 65 or have low testosterone levels.

This round of treatment, known as neoadjuvant ADT, may be prescribed with a view to improving odds for patients who have some adverse markers.

Led by  Prof. Masatoshi Eto, the Japanese team analyzed results for 711 patients with clinically localized prostate cancer who were treated with radical prostatectomy (RP) between 2000 and 2013. Some patients underwent androgen deprivation therapy before the surgery, some did not.The patients were treated with open RP, laparoscopic RP, or robot-assisted laparoscopic RP at Kyushu University Hospital (Fukuoka, Japan).

None of the patients showed signs of advanced cancer on scans or from their prior medical history. “Patients diagnosed with metastasis by imaging modalities including computed tomography scan and bone scan and patients with a history of neoadjuvant/adjuvant radiotherapy or chemotherapy and adjuvant ADT against prostate cancer were excluded,” the authors state.

The study looked for any difference in rate of biochemical recurrence (BCR) after the surgery.  BCR is defined as rise in the blood level of PSA (prostate-specific antigen) in prostate cancer patients after treatment with surgery or radiation. Biochemical recurrence may occur in patients who do not have symptoms. It may mean that the cancer has come back.

In a period of median 2 years, biochemical recurrence occurred in more than quarter of the patients (186 [26.2%] of 711).  Analysis indicated that neoadjuvant ADT in and of itself did not cause and was not associated with the risk of biochemical recurrence.

The group treated with ADT before surgery showed higher PSA at diagnosis and more advanced clinical T-stage, but suppressed pathological T-stage.

In subgroup analysis, neoadjuvant ADT was significantly associated with increased biochemical recurrence in patients aged 65 years and older. Also, among the 53 patients with available serum testosterone levels, for those with low testosterone the risk of biochemical recurrence  was found to be higher. 

The authors say: “Low serum testosterone levels before treatment may represent a reduced androgen dependency of the prostate cancer, which would be less effectively repressed by ADT.” So, they write, “both age and serum testosterone level may be common predictive markers for the efficacy of ADT and may serve as parameters for selection of candidates suitable for neoadjuvant ADT.”

To sum up —  according to the evidence analyzed in this study, androgen blockade before surgery may not work well for prostate cancer patients  above 65 and/or with lower testosterone levels. On the other hand, ADT before surgery may (as intended) improve prognosis for patients with high serum testosterone  levels. The situation, the authors conclude, warrants further exploration. Read more details in the free, full text article linked below.

Another recent study, in France, found that “Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen. This observation should be taken into account in localised PCa management, especially for active surveillance or when a nerve-sparing approach is considered.”

Another recent French study set out to “prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP).” Their data suggested that of these factors, only low “bioavailable testosterone (BT) and free testosterone (FT)” levels, “which might logically result in an active androgen-depleted environment, were linked with high-grade PCa.”

Sources:

Neoadjuvant androgen-deprivation therapy with radical prostatectomy for prostate cancer in association with age and serum testosterone

Prostate international. 2017 Nov 21 [Epub]  Naoko Akitake, Masaki Shiota, Hirofumi Obata, Ario Takeuchi, Eiji Kashiwagi, Kenjiro Imada, Keijiro Kiyoshima, Junichi Inokuchi, Katsunori Tatsugami, Masatoshi Eto.  Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading

Prostate Cancer and Prostatic Diseases volume 18 (2015)

Low circulating free and bioavailable testosterone levels as predictors of high-grade tumors in patients undergoing radical prostatectomy for localized prostate cancer.

Urol Oncol. 2015 Sep;33(9)