Indian Journal of Urology
UROSCAN
Year
: 2010  |  Volume : 26  |  Issue : 1  |  Page : 152--153

Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: Where is the evidence?


TJ Nirmal, S Kumar 
 Department of Urology, Christian Medical College, Vellore, India

Correspondence Address:
T J Nirmal
Department of Urology, Christian Medical College, Vellore
India




How to cite this article:
Nirmal T J, Kumar S. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: Where is the evidence?.Indian J Urol 2010;26:152-153


How to cite this URL:
Nirmal T J, Kumar S. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: Where is the evidence?. Indian J Urol [serial online] 2010 [cited 2020 Oct 22 ];26:152-153
Available from: https://www.indianjurol.com/text.asp?2010/26/1/152/60470


Full Text

 Summary



This multicenter, phase III, randomized study compares intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer. [1] Men below 80 years of age, with histologically confirmed prostate cancer of stage T3 and above, with or without metastasis; and a prostate specific antigen (PSA) level ≥4 to [2] It helps to palliate, delay or prevent the onset of symptoms related to the disease and its complications but does not improve overall survival. [2] Majority of the patients on continuous therapy become vulnerable to its various side effects and ultimately progress to hormone resistant prostate cancer (HRPC) in two to three years. [3] The concept of IHT for prostate cancer and its beneficial effect on QoL was first clinically described by Klotz et al., in 1986. IHT in murine models (lymph node cancer of the prostate [LNCaP] and Shionogi carcinoma significantly delayed the onset of HRPC [4] and heralded the beginning of various clinical trials. Over the years, >20 phase two trials which have included >2000 patients have evaluated the feasibility, efficacy, and safety of IHT. [5] It is apparent that IHT has a beneficial effect on QoL and has additional advantages in terms of reduced health care costs. However, the two essential questions to be answered are:



Does IHT delay the onset of hormone resistance?Can IHT improve overall survival?IHT seems to fall short of expectations in the randomized phase III study by Calais da silva et al. It is known that patients with bulky disease, bone metastasis and PSA levels >100 ng/ ml have a poor response to IHT. [6] Hence, majority of the patients included in this study had asymptomatic, non-metastatic T3 disease and a Gleason score of ≤7. A later amendment restricted entry to PSA [7] or take antiandrogens to avoid side-effects of castration.

The highlight of the SEUG trial is the fact that it used a three- month induction period without any demonstrable impact on survival unlike previous trials advocating six to nine months. [8] At three months of induction, 81% of the patients were able to achieve a PSA nadir of [5] relative to continuous therapy but is still not comparable to the cost effectiveness of orchiectomy.

Results of the SEUG trial only fuel the debate as to whether the "average improvement in QoL" offered by IHT stands up to the "average improvement in quantity of life" promised by the conventional continuous therapy.

To conclude, the SEUG trial doesn't give us sufficient evidence to recommend its routine clinical use and we must await the results of other phase III trials to define a patient population most likely to benefit from IHT.

References

1Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, et al. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: Results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol 2009;55:1269-77.
2Heidenreich A, Aus G, Bolla M, oniau S, Matveev VB, Schmid HP, et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68-80.
3Robinson MR, Smith PH, Richards B, Newling DW, de Pauw M, Sylvester R. The final analysis of the EORTC Genito-Urinary Tract Cancer Co-operative Group Phase III clinical trial (Protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate, and low dose stilboestrol in the management of metastatic carcinoma of the prostate. Eur Urol 1995;28:273-83.
4Akakura K, Bruchovsky N, Goldenberg SL, Rennie PS, Buckley AR, Sullivan LD. Effects of intermittent androgen suppression on androgen-dependent tumors. Apoptosis and serum prostate-specific antigen. Cancer 1993;71:2782-90.
5Tunn U. The current status of intermittent androgen deprivation (IAD) therapy for prostate cancer: Putting IAD under the spotlight. BJU Int 2007;99:19-22.
6Salonen AJ, Viitanen J, Lundstedt S, Ala-Opas M, Taari K, Tammela TL. Finnish multicenter study comparing intermittent to continuous androgen deprivation for advanced prostate cancer: Interim analysis of prognostic markers affecting initial response to androgen deprivation. J Urol 2008;180:915-9.
7Hussain M, Tangen CM, Higano C, Schelhammer PF, Faulkner J, Crawford ED, et al. Absolute prostatespecific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: Data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol 2006;24:3984-90.
8Studer UE, Whelan P, Albrecht W, Casselman J, de Reijke T, Hauri D, et al. Immediate or tdeferred androgen deprivation for patients with prostate cancer not suitable for local treatmentwithcurative intent: European Organization for Research and Treatment of Cancer (EORTC) Trial 30891. J Clin Oncol 2006;24:1868-76.