Computed tomography/magnetic resonance based volume changes of the primary tumour in patients with prostate cancer with or without androgen deprivation
Introduction
Prostate cancer has become the most common cancer in men in the Western countries, and the incidence is increasing. Only patients with prostate cancer confined to the gland (pT1-T2N0M0) are true candidates for curative treatment, either by radical prostatectomy or definitive radiotherapy. In patients with metastatic disease androgen deprivation (AD) has represented the standard palliative treatment in case of distant metastases. However, the optimal treatment for patients with loco-regionally advanced disease remains controversial [6], [16]. In asymptomatic patients one principal question is whether hormone manipulation should be started immediately after diagnosis or after clinical progression.
During the last decade medical AD has been used as neoadjuvant treatment before radical prostatectomy or high dose radiotherapy with the aim to reduce the prostatic volume. The main expectation was that such ‘downsizing’ would reduce the number of patients with tumour positive margins in the prostatectomy specimen or would facilitate the use of reduced target volumes during radiotherapy [1], [12]. So far, pre-prostatectomy neo-adjuvant hormone treatment has, however, not shown to increase overall survival, whereas the combination of radiotherapy with long-lasting AD has confirmed a beneficial overall survival in at least one study [3].
Usually, a 3 month period of treatment with a LHRH-agonist (luteinizing hormone releasing hormone) is recommended (with or without anti-androgens) before curative local treatment [10], [12], [15]. The optimal duration of neoadjuvant hormone treatment has, however, never been scientifically established. On the other hand, experience from metastatic patients suggests that more than 3 months of AD is necessary to achieve the maximal volume reduction of the prostate [2], [14] or nadir values of prostate specific antigen (PSA) [8]. The answer to the question about the duration of pre-radiotherapy neoadjuvant AD that leads to maximal volume reduction has significant impact in clinical radiation oncology. Radiobiological considerations suggest that dose escalation of >70 Gy in the 95% isodose is necessary to eradicate adenocarcinoma. Conformal radiotherapy makes such dose increase feasible, but requires the smallest possible target volume to protect normal tissue [4], [9], [11].
Localized prostate cancer is usually regarded as a slowly growing malignancy [5], [15]. A delay of 1–3 months between the initial diagnosis and definitive treatment is most often considered to be without clinical relevance. Delay periods of greater than 3 months are, however, not unusual due to the hospital waiting lists and/or lengthy staging procedures as pelvic lymphadenectomy. The question remains whether and how often significant growth of the prostatic tumour can be observed during the initial months after diagnosis.
Obviously more objective information about the size changes of hormonally treated or untreated prostate cancer is desirable in order to establish which time interval between diagnosis and local curative treatment may be allowed to elapse in clinical practice. With this background we have investigated the effect of 1 year's AD on the volume of the cancerous prostatic gland if treatment was started immediately after diagnosis. We were interested to determine the duration of neo-adjuvant hormonal treatment, that within the 1st year resulted in maximal pre-radiotherapy downsizing of the prostatic gland.
As our investigated patients were randomized against a ‘non-treated’ control arm, we also had the possibility to study the volume change of the prostate during 1 year if no hormone manipulation was initiated, thus assessing the growth pattern of the cancerous prostate gland.
Section snippets
Patients and methods
In 1986 the EORTC-GU group initiated a phase III trial with T1 to T 3pN+M0 prostate cancer which in asymptomatic patients compared immediate androgen deprivation (IAD) with delayed androgen deprivation (DAD) and start of therapy in case of clinical progression (EORTC 30846). From the time of randomization patients within the IAD arm received 3.6 mg LHRH analogue (Zoladex®, Zeneca) every 4 weeks subcutaneously together with oral cyproterone acetate (Androcur®, Schering) 150 mg pd. during the 1st
Results
At randomization the two patients cohorts were similar in terms of age, pN status and tumour category (Table 1), though the mean volume of the DAD group was above that of the IAD group. This difference did not reach statistical significance.
In the IAD group the prostate gland size decreased in all patients with significant difference as compared with the DAD group (P=0.033, Fig. 2a,b). Pairwise comparison of mean values confirmed the volume reduction at months 1, 3 and 9 (P<0.05, Table 2).
Discussion
In the present study only 13 patients in the IAD group and 13 patients in the DAD group are investigated. These were those patients who were included in the EORTC trial 30846 by our institution. This trial required regular assessments of the prostate gland, preferably measured by ultrasonography. No other institution used CT/MR for such measurements. The results of our admittedly limited series are in agreement with analogue observations from other though not radiotherapy-related studies. We
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