Treatment options for localized prostate cancer (CaP) are controversial, with proponents of surgical treatment,<sup>11 Catalona W.J. Surgical management of prostate cancer: Contemporary results with anatomical radical prostatectomy Cancer 1995 ;  75 : 1903  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 78 Paulson D.F. Impact of radical prostatectomy in the management of clinically localized disease J Urol 1994 ;  152 : 1826-1830

Cliccare qui per andare alla sezione Riferimenti, 105 Stapleton A.M.F., Scardino P.T. Nerve-sparing radical retropubic prostatectomy Operative Urology London: Churchill Livingstone (1996). 

Cliccare qui per andare alla sezione Riferimenti, 116 Walsh P.C. Radical retropubic prostatectomy with reduced morbidity: An anatomic approach NCI Monogr 1988 ;  7 : 133-148

Cliccare qui per andare alla sezione Riferimenti</sup> radiation therapy,<sup>7 Bagshaw M.A., Cox R.S., Hancock S.L. Control of prostate cancer with radiotherapy: The long-term results J Urol 1994 ;  152 : 1781

Cliccare qui per andare alla sezione Riferimenti, 44 Hanks G.E., Hanlon A., Schultheiss T. , e al. Early prostate cancer: The national results of radiation treatment from the patterns of care and radiation therapy oncology group studies with prospects for improvement with conformal radiation and adjuvant androgen deprivation J Urol 1994 ;  152 : 1775

Cliccare qui per andare alla sezione Riferimenti, 93 Shipley W.U., Zietman A.L., Hanks G.E. , e al. Treatment related sequelae following external beam radiation for prostate cancer: A review with an update in patients with stages T1 and T2 tumor J Urol 1994 ;  152 : 1799

Cliccare qui per andare alla sezione Riferimenti, 120 Zagars G.K. Prostate specific antigen as an outcome variable for T1 and T2 prostate cancer treated by radiation therapy J Urol 1994 ;  152 : 1786

Cliccare qui per andare alla sezione Riferimenti</sup> and conservative management.<sup>15 Chodak G.W. Treatment of early stage prostate cancer: Conservative management-delayed therapy Important Advances in Oncology Philadelphia: JB Lippincott (1994).  241-244

Cliccare qui per andare alla sezione Riferimenti, 16 Chodak G.W., Thisted R.A., Gerber G.A. , e al. Results of conservative management of clinically localized prostate cancer N Engl J Med 1994 ;  330 : 242-248  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 46 Johansson J.E. Expectant management of early stage prostate cancer: Swedish experience J Urol 1994 ;  152 : 1753-1756

Cliccare qui per andare alla sezione Riferimenti, 119 Warner J., Whitmore W.F. Expectant management of clinically localized prostate cancer J Urol 1994 ;  152 : 1761-1765

Cliccare qui per andare alla sezione Riferimenti</sup> 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 reports<sup>2 Adolfsson J., Steineck G., Whitmore W.F. Recent results of management of palpable clinically localized prostate cancer Cancer 1993 ;  72 : 310-322  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 78 Paulson D.F. Impact of radical prostatectomy in the management of clinically localized disease J Urol 1994 ;  152 : 1826-1830

Cliccare qui per andare alla sezione Riferimenti, 106 Stein A., DeKernion J.B., Smith R.B. , e al. Prostate specific antigen levels after radical prostatectomy in patients with organ confined and locally extensive prostate cancer J Urol 1992 ;  147 : 942-946

Cliccare qui per andare alla sezione Riferimenti, 118 Walsh P.C., Partin A.W., Epstein J.I. Cancer control and quality of life following anatomical radical retropubic prostatectomy: Results at 10 years J Urol 1994 ;  152 : 1831-1836

Cliccare qui per andare alla sezione Riferimenti</sup> 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.<sup>35 Gibbons R.P., Correa R.J., Brannen G.E. , e al. Total prostatectomy for clinically localized prostate cancer: Long-term results J Urol 1989 ;  141 : 564-566

Cliccare qui per andare alla sezione Riferimenti, 78 Paulson D.F. Impact of radical prostatectomy in the management of clinically localized disease J Urol 1994 ;  152 : 1826-1830

Cliccare qui per andare alla sezione Riferimenti, 109 Trapasso J.G., deKernion J.B., Smith R.B. , e al. Incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy J Urol 1994 ;  152 : 1821-1825

Cliccare qui per andare alla sezione Riferimenti, 121 Zincke H., Oesterling J.E., Blute M.L. , e al. Long term (15 years) results after radical prostatectomy for clinically localized (stage t2c or lower) prostate cancer J Urol 1994 ;  152 : 1850-1857

Cliccare qui per andare alla sezione Riferimenti</sup> 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).<sup>13 Catalona W.J., Smith D.S. 5-Year tumor recurrence rates after anatomical radical retropubic prostatectomy for prostate cancer J Urol 1994 ;  152 : 1837-1842

Cliccare qui per andare alla sezione Riferimenti, 77 Partin A.W., Pound C.R., Clemens J.Q. , e al. Serum PSA after anatomic radical prostatectomy: The Johns Hopkins experience after 10 years Urol Clin North Am 1993 ;  20 : 713-725

Cliccare qui per andare alla sezione Riferimenti, 109 Trapasso J.G., deKernion J.B., Smith R.B. , e al. Incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy J Urol 1994 ;  152 : 1821-1825

Cliccare qui per andare alla sezione Riferimenti, 121 Zincke H., Oesterling J.E., Blute M.L. , e al. Long term (15 years) results after radical prostatectomy for clinically localized (stage t2c or lower) prostate cancer J Urol 1994 ;  152 : 1850-1857

Cliccare qui per andare alla sezione Riferimenti</sup> 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,<sup>105 Stapleton A.M.F., Scardino P.T. Nerve-sparing radical retropubic prostatectomy Operative Urology London: Churchill Livingstone (1996). 

Cliccare qui per andare alla sezione Riferimenti, 117 Walsh P.C., Partin A.W. Treatment of early stage prostate cancer: Radical prostatectomy Important Advances in Oncology Philadelphia: JB Lippincott (1994).  211-223

Cliccare qui per andare alla sezione Riferimenti</sup> safer anesthesia, and improved perioperative and postoperative care have minimized the associated morbidity. The reported mortality is less than 0.5%.<sup>11 Catalona W.J. Surgical management of prostate cancer: Contemporary results with anatomical radical prostatectomy Cancer 1995 ;  75 : 1903  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Recently, decision-analysis models<sup>8 Beck J.B., Kattan M.W., Miles B.J. A critique of the decision analysis for clinically localized prostate cancer J Urol 1994 ;  152 : 1894-1899

Cliccare qui per andare alla sezione Riferimenti, 32 Fleming C., Wasson J.H., Albertsen P.C. , e al. A decision analysis of alternative treatment strategies for clinically localized prostate cancer JAMA 1993 ;  269 : 2650-2658

Cliccare qui per andare alla sezione Riferimenti, 49 Kattan M.W., Miles B.J., Beck J.R. , e al. Re-examination of the decision analysis for clinically localized prostate cancer: Age and grade comparisons J Urol 1995 ;  153 : 390A

Cliccare qui per andare alla sezione Riferimenti, 50 Kattan M.W., Miles B.J., Beck J.R. , e al. Second order Monte Carlo simulation in the decision to treat clinically localized prostate cancer Med Decis Making 1995 ;  15 : 429

Cliccare qui per andare alla sezione Riferimenti, 64 Miles B.J., Kattan M.W. Computer modeling of prostate cancer treatment: A paradigm for oncologic management? Surg Oncol Clin North Am 1995 ;  4 : 361

Cliccare qui per andare alla sezione Riferimenti, 86 Scardino P.T., Beck J.R., Miles B.J. Conservative management of prostate cancer. N Engl J Med 330:1831, 1994: editorial comment on Chodak GW, Thisted RA, Gerber GS, et al: Results of conservative management of clinically localized prostate cancer N Engl J Med 1994 ;  330 : 242-248

Cliccare qui per andare alla sezione Riferimenti</sup> and quality-of-life studies<sup>33 Fowler F.J., Barry M.J., Lu-Yao G. , e al. Effect of radical prostatectomy for prostate cancer on patient quality of life: Results from a medicare survey Urology 1995 ;  45 : 1007

Cliccare qui per andare alla sezione Riferimenti, 61 Lim A.J., Brandon A.H., Fiedler J. , e al. Quality of life: Radical prostatectomy versus radiotherapy for prostate cancer J Urol 1995 ;  154 : 1420  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> 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.<sup>34 Gee W.F., Holtgrewe H.L., Albertsen P.C. , e al. Practice trends in the diagnosis and management of prostate cancer in the United States J Urol 1995 ;  154 : 207-208  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>

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.<sup>25 Epstein J.I., Pizov G., Walsh P.C. Correlation of pathologic findings with progression after radical retropubic prostatectomy Cancer 1993 ;  71 : 3582-3593  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 73 Ohori M., Wheeler T.M., Kattan M.W. , e al. Prognostic significance of positive surgical margins in radical prostatectomy specimens J Urol 1995 ;  154 : 1818-1824  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 79 Paulson D.F., Moul J.W., Walther P.J. Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: Long-term results J Urol 1990 ;  144 : 1180-1184

Cliccare qui per andare alla sezione Riferimenti</sup> 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.<sup>24 Epstein J.I., Carmichael M., Partin A.W. , e al. Is tumor volume an independent predictor of progression following radical prostatectomy? A multivariate analysis of 185 clinical stage B adenocarcinomas of the prostate with 5 years of followup J Urol 1993 ;  149 : 1478-1485

Cliccare qui per andare alla sezione Riferimenti, 101 Stamey T.A., Freiha F.S., McNeal J.E. , e al. Localized prostate cancer: Relationship of tumor volume to clinical significance for treatment of prostate cancer Cancer 1993 ;  71 : 933-938  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 103 Stamey T.A., Villers A.A., McNeal J.E. , e al. Positive surgical margins at radical prostatectomy: Importance of apical dissection J Urol 1990 ;  143 : 1166-1173

Cliccare qui per andare alla sezione Riferimenti</sup> 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.