30 maart 2011: Bron: The Lancet en Cancer Manag Res. 2010; 2: 243–253

Prostaatkankerpatienten met lokale uitzaaiingen hebben het meeste profijt van een gecombineerde aanpak van hormoontherapie gedurende 6 maanden plus uitwendige bestraling. Dit blijkt uit de nieuwste resultaten van de TROG studie, een grote langjarige gerandomiseerde fase III studie die in meerdere ziekenhuizen al jaren wordt uitgevoerd. Tot nu toe werd standaard drie maanden hormoontherapie plus bestraling geven of alleen bestraling maar nu blijkt uit de nieuwste studieresultaten dat na 10 jaar in de groep die 6 maanden de combibehandeling kreeg er 11% was overleden na 10 jaar tegenover 22% in de groep die alleen bestraling had gekregen. Over deze studie zijn veel gegevens publiekelijk gemaakt. Ik heb er twee uitgekozen. Een volledig studieverslag over de stand van zaken bij lokaal uitgezaaide prostaatkanker waarvan het hele studieverslag als u hier klikt kan worden ingezien inclusief goede informatie over de bijwerkingen van de behandelingen. En een artikel uit Medscape over de nieuwste studieresultaten. Hieronder enkele citaten ook daaruit. Als laatste staat onderaan het abstract van de laatste studie gepubliceerd in The Lancet, waar u tegen betaling het volledige studierapport kunt inzien.

De conclusies uit de studie uit 2010:

Remarks and conclusions

In the high-risk group of patients, combined treatment (RT–HT) produced therapeutic gain. For intermediate-risk patients, we have the first results of clinical trials RTOG 94-08, suggesting a statistically significant benefit. More precise conclusion can be made after the results of RTOG 99-10 trial. For low-risk PC patients, combined EBRT–ADT has no role in contemporary treatment guidelines. On the basis of the data reviewed from the literature, it can be concluded as follows:

ADT is easy to administer and requires no special technology. Neoadjuvant, concurrent, and long-term adjuvant androgen deprivation is standard treatment in conjunction with radiation therapy in the group of patients with high risk of failure (T3, PSA > 20 ng/mL, GS > 7). Neoadjuvant, concurrent ADT, and short-term adjuvant should be individually decided in intermediate-risk patients.
The optimal timing for application of androgen depletion has not yet been precisely determined. According to the current state of knowledge, approximately 2–3 months for neoadjuvant therapy is probably the optimal strategy. The best mode of neoadjuvant HT is represented by chemical castration combined with short antiandrogen treatment in the initial phase. Neoadjuvant HT should always be followed by ADT concurrent with RT. Adjuvant HT is recommended for high-risk patients for at least 2 years, but longer treatment could be beneficial, provided the toxicity of ADT is not of concern because of patient comorbidities. Studies have shown a survival benefit for patients with more advanced disease when longer adjuvant androgen suppression treatment was applied (3 years).

Enkele citaten uit Medscape artikel:

Six Months Superior to 3 Months

The TROG 96.01 study compared radiotherapy alone with 3 or 6 months of neoadjuvant ADT, which was given before and during radiation therapy. In their paper, the authors report, from the 10-year data, the benefits derived from 3 months and 6 months of neoadjuvant ADT.

Their analysis involved 802 men with stage T2b, T2c, T3, and T4 N0M0 prostate cancers. They were randomly assigned to receive radiotherapy alone (n = 270), 3 months of neoadjuvant ADT plus radiotherapy (n = 265), or 6 months of neoadjuvant ADT plus radiotherapy (n = 267).

At 10 years, prostate-cancer-specific mortality was 22% for radiotherapy alone, 18.9% for 3 months of neoadjuvant therapy (hazard ratio , 0.86; P = .398), and 11.4% for 6 months of neoadjuvant ADT (HR, 0.49; P = .0008).

For all-cause mortality at 10 years, the findings were similar: 42.5% for radiotherapy alone, 36.7% for 3 months of neoadjuvant ADT (HR, 0.84; P = .18), and 29.2% for 6 months of neoadjuvant ADT (HR, 0.63; P = .0008).

Conversely, the cumulative incidence of deaths at 10 years not related to prostate cancer were similar in all treatment groups: 20.4% for radiotherapy alone, 17.7% for 3 months of neoadjuvant ADT, and 17.8% for 6 months of neoadjuvant ADT (P > .40 for all paired comparisons).

During the course of the study, 16,562 PSA levels were obtained from the 802 men; the median number of PSA levels per patient was 21 (range, 1 to 43).

Progression of PSA was observed in 508 men. At 10 years, the cumulative incidence of PSA progression was 73.8% for radiotherapy alone, 60.4% for 3 months of neoadjuvant ADT (HR, 0.72; P = .003), and 52.3% for 6 months of neoadjuvant ADT (HR, 0.57; P < .0001).

Progression of the primary tumor was found in 179 men, and progression at distant sites was found in 226 men. The 10-year cumulative incidence of local progression as a first event was 28.2% for radiotherapy alone, 15.7% for 3 months of neoadjuvant ADT (HR, 0.49; P = .0005), and 13.3% for 6 months of neoadjuvant ADT (HR, 0.45; P < .0001).

Uit The Lancet:

Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial

Prof James W Denham MD a

, Allison Steigler BMath a, Prof David S Lamb FRANZCR b, Prof David Joseph FRANZCR c, Sandra Turner FRANZCR d, John Matthews FRANZCR e, Chris Atkinson FRANZCR f, John North FRANZCR g, David Christie FRANZCR h, Prof Nigel A Spry FRANZCR c, Keen-Hun Tai FRANZCR i, Chris Wynne FRANZCR f, Prof Catherine D'Este PhD j

Summary

Background

The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results.

Methods

Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5—7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482.

Findings

802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9—11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57—0·90; p=0·003) and local progression (0·49, 0·33—0·73; p=0·0005), and improved event-free survival (0·63, 0·52—0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46—0·72; p<0·0001) and local progression (0·45, 0·30—0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42—0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60—1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60—1·23; p=0·398), or all-cause mortality (0·84, 0·65—1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31—0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32—0·74; p=0·0008), and all-cause mortality (0·63, 0·48—0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation.

Interpretation

6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation.