Unfortunately this debate remained controversial. However some information before

selection of treatment should be clarified: First, what was the initial treatment, if a radical prostatectomy has been performed (i.e. localized cancer), then evaluation of the surgical site for relapse is mandatory, and if the local relapse verified, the surgical intervention or radiotherapy may be rational than (or in adjunct with) systemic hormonal therapy. But if it proves only rising PSA (PSA only recurrence) after failed therapy, this is controversial but local salvage therapy (radiotherapy) or systemic approach (mainly androgen deprivation:LHRH agonist. the duration of these course , certainly depends on the velocity of PSA decrease. Second, if the case is an early hormone refractory prostate cancer without metastasis, LHRH agonist or Chemotherapy may be prescribed. Although in all these cases the treatment should be individualized respect to the risk factors (risk stratified) and life expectancy.

Regards

Rising PSA, if thought to be due to micrometastatic disease, is often treated with androgen deprivation therapy (ADT) by LHRH agonist (or newer antagonist) - even if mets not seen on scans. The optimal PSA level to start ADT for such patients is unknown. In the setting where they have had previous local therapy and relapsed, my practice is to start treatment when the PSA gets to the pre-treatment level. In the de-novo setting, I have followed PSAs up to 100 or so before starting treatment. Delayed start to ADT potentially reduces ADT side effects and morbidity.

Adjuvant therapy following surgery usually takes the form of radiotherapy - indication being extra-prostatic extension and/or positive surgical margins - ie risk of residual local disease. Adjuvant ADT may occasionally be given for node positive patients, but the level of evidence is weaker and these patients are rarer.

1. The rule of thumb is you start ADT when PSA reaches 50 ng/ml even bone scan is negative for hot spots. Especially when you work in a region where patient compliance is poor and may not attend follow up regularly.

However for locally advanced disease or high risk organ confined disease you may give a limited course of ADT as adjuvant therapy to radical surgery or radiotherapy.

2. 18-24 months

This question includes a variety of settings of prostate cancer.

Thus, I answer only in the context of surgery.

According to the current guidelines in Europe and the US, the initial use of ADT after surgery is justified only for pN1 (i.e. positive regional lymph node metastasis) patients. Otherwise, radiotherapy is used as the first-line treatment: adjuvant radiotherapy for high-risk post-prostatectomy patients other than pN1 (e.g. pT≧3, RM+, etc); salvage radiotherapy for biochemical recurrence after radical prostatectomy.

This algorithm is based on several RCTs, and may imply that radiotherapy is superior in local control to ADT, while ADT should be chosen when the disease is considered to be not localized (e.g. pN1).

It is to be noted that in Asia ADT is used as first-line treatment along with radiotherapy, both in adjuvant and salvage settings (The Asia Consensus Statement in the NCCN Clinical Practice Guidelines).

PSA as its name says, is a prostate specific antigen. Therefore, it is not about how much total PSA is elevated. Rather, it is about RATIO between total and free and bound PSA. If the ratio is within normal limits, eg. up to 6 ng/ml) the situation is still under control. ADT in that case might be given not because of cancer but because of enlarged prostate from hormonal reasons.

Sorry Hamsa, I disagree with your answer:

Dear Sabine

First of all according to the literature, androgen deprivation therapy (by LHRL) (ADT) has 3 relevant usage in prostate cancer:

1- In radiation therapy of localized prostate cancer as a mean of adjuvant therapy; there we advise patients to recieve ADT either for 6 months to 3 years according to the risk stratification

2- In immediate or delayed/salvage radiation therapy of high risk prostate cancer patients due to the pathological features

3- In metastatic patients; Differentiation of local recurrences from metastasis is the most significant problem encountered in radiation treated prostate cancer cases.

The following are EORTC trials where ADT is used in combination of radiotherapy for treatment of prostate cancer

EORTC-22043-30041-ROG-GUCG - 30041: Immediate or early salvage post-operative external radiotherapy combined with concomitant and adjuvant hormonal treatment versus immediate or early salvage post-operative external radiotherapy alone in pT3a-b R0-1 cNOMO/pT2R1 cN0M0, Gleason score 5-10 prostatic carcinoma. A phase III study.

EORTC-22961-ROG-GUCG: Long term adjuvant hormonal treatment with LHRH analogue versus no further treatment in locally advanced prostatic carcinoma treated by external irradiation and a six months combined androgen blockade - A phase III study. (Joint study of the EORTC Radiotherapy Cooperative Group and the EORTC Genito-Urinary Tract Cancer Cooperative Group)

EORTC-22991-ROG: Three Dimensional Conformal Radiotherapy / Intensity Modulated Radiotherapy alone vs Three Dimensional Conformal Radiotherapy / Intensity Modulated Radiotherapy plus adjuvant hormonal therapy in localized T1b-c, T2a, N0, M0 prostatic carcinoma. A Phase III Randomized Study.

EORTC-22863-ROG-GUCG: Phase III randomized clinical trial in high metastatic risk carcinoma of the prostate comparing pelvic radiotherapy plus LHRH analogue (Jointly with the EORTC Genito-Urinary Cancers Group)

EORTC-1201-GUCG-ROG - PEACE-1: A prospective randomised phase III study of androgen deprivation therapy with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer

On the other hand unfortunately some doctors tend to treat localized prostate cancer with a ADT monotherapy which is a misuse. These doctors have the licence to prescribe such drugs but lack the knowledge.

a recent study presented at ASCO showed there was no benefit in early ADT for PSA relapse,until the occurence of clinical metastatic disease