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Urologic Clinics of North America

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WHY NEOADJUVANT ANDROGEN DEPRIVATION PRIOR TO RADICAL PROSTATECTOMY IS UNNECESSARY - 11/09/11

Doi : 10.1016/S0094-0143(05)70338-4 
Farhat Abbas, MD *, Peter T. Scardino, MD *

Resumen

Treatment options for localized prostate cancer (CaP) are controversial, with proponents of surgical treatment,11, 78, 105, 116 radiation therapy,7, 44, 93, 120 and conservative management.15, 16, 46, 119 Conceptually, an optimum treatment strategy should provide long-term disease-free survival, with minimum treatment-related morbidity and maximum preservation of life. Though the ideal treatment is still not available, recent reports2, 78, 106, 118 document that radical prostatectomy (RP) is highly effective in eradicating the cancer and can be performed with greatly reduced morbidity.

Following surgical treatment for T1 to T2 disease, the cancer-specific survival rate is 90% to 94% at 10 years and 82% to 90% at 15 years.35, 78, 109, 121 Using prostate-specific antigen (PSA) as an indicator of progression, the reported nonprogression rate for clinically localized CaP is 69% to 83% at 5 years and 47% to 77% at 10 years (Table 1).13, 77, 109, 121 In a series of 725 patients treated at Baylor with no other cancer-directed therapy before or after the operation, the PSA-based nonprogression rate in 694 patients with available follow-up was 78% at 5 years and 71% at 10 years (Figure 1). For cancers confined to the prostate pathologically (58%), the nonprogression rate is greater than 90% at 5 and 10 years (Figure 2). Refinements in surgical technique of anatomic RP,105, 117 safer anesthesia, and improved perioperative and postoperative care have minimized the associated morbidity. The reported mortality is less than 0.5%.11 Recently, decision-analysis models8, 32, 49, 50, 64, 86 and quality-of-life studies33, 61 support the benefit of active treatment with RP over conservative management in appropriate patients. Taken together, this experience has led to a sixfold increase in the number of RPs performed during the last 10 years in the United States for localized CaP.34

Nevertheless, concern has been raised about the efficacy of RP as monotherapy because of pathologic upstaging in nearly half of all patients and a high rate of positive surgical margins. Positive surgical margins have been associated with a greater risk of progression.25, 73, 79 The rate of positive margins correlates with the volume and location of the primary tumor and, most importantly, the tumor's extent or pathologic stage.24, 101, 103 Because androgen deprivation has clearly been shown to decrease the size of CaP, both locally and at metastatic sites, neoadjuvant androgen deprivation therapy or neoadjuvant hormonal therapy (NHT) has been advocated to “downstage” the tumor prior to surgical resection. Because NHT reduces the incidence of apparent positive surgical margins, the implication is that NHT improves the likelihood of disease-free survival.

With the data available today, NHT cannot be considered standard therapy for several reasons. (1) Most studies on the role of NHT are uncontrolled and involve small numbers of patients. Only a few randomized trials have been published, and none of these provide data about progression after RP. (2) Although NHT produces marked physiologic effects, with reduction in serum PSA levels, prostate size, and tumor volume, the data on pathologic downstaging is conflicting. (3) Despite lowering the apparent rate of positive surgical margins, NHT does not reduce the probability of nodal metastases or of seminal vesicle involvement. (4) Because the cancer within the prostate is rarely eradicated, there is no current scientific basis to suppose that all cancer outside the prostate is eliminated. The apparent reduction in the rate of positive surgical margins may be an artefact of specimen processing or histologic examination. (5) The rate of positive surgical margins in control patients of NHT studies is extraordinarily high, compared with contemporary published series, raising the question whether the surgical technique was adequate. (6) Few studies provide data about progression rates after surgery in NHT-treated patients. (7) There is no evidence that NHT prolongs time to progression or disease-free survival in any subset of patients.

Currently, there is no established benefit of combination therapy with NHT over RP alone. Because there is serious concern about the validity and biologic significance of the apparent downstaging and decreased rate of positive margins, and no evidence of improved time to progression and survival, NHT is not advisable outside of a clinical trial. NHT may have distinct disadvantages as well (see later). Until the ongoing randomized trials demonstrate a favorable effect on progression or survival, we do not recommend the routine use of NHT before RP.

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 Address reprint requests to Peter T. Scardino, MD, Scott Department of Urology, Baylor College of Medicine, 6560 Fannin, Suite 2100, Hoston, TX 77030
This work is supported in part by the Specialized Program of Research Excellence (SPORE) grant (CA58204) from the National Cancer Institute.


© 1996  W. B. Saunders Company. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 23 - N° 4

P. 587-604 - novembre 1996 Regresar al número
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  • THE ROLE OF NEOADJUVANT ANDROGEN DEPRIVATION PRIOR TO RADICAL PROSTATECTOMY
  • Yves Fradet
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  • LONG-TERM CONTROL OF PROSTATE CANCER WITH RADIATION : Past, Present, and Future
  • Gerald E. Hanks

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