AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

Over the last 15 years, public awareness of prostate cancer prevention, detection, and treatment has increased. The combined use of improved diagnostic modalities, such as prostate-specific antigen (PSA) score, digital rectal examination (DRE), and transrectal ultrasound (TRUS)–guided prostate biopsy, has contributed to a rapid rise in prostate cancer detection. Increased detection has changed the age and stage distribution of the disease, dramatically increasing the diagnosis of clinically localized and potentially curable prostate cancer. Most institutions report a shift in clinical stage from locally advanced (T3) to clinically organ–confined (T1-T2) tumors that are more amenable to curative treatment.

The optimal treatment of clinically localized prostate cancer remains a matter of debate. In patients with organ-confined disease, radical prostatectomy (RP) provides an excellent chance of cure. However, the high incidence of clinical understaging due to the lack of sensitivity of currently available staging modalities has tempered the enthusiasm for surgery. Although the serum PSA level generally reflects tumor volume, it is not a reliable marker for tumor staging. Free PSA, PSA density, and ploidy status are also imperfect markers. DRE findings often underestimate the extent of tumor. The results from TRUS, CT scan, and endorectal MRI have been disappointing.

Even among nonpalpable tumors (T1c) treated with RP, the incidence rate of capsular penetration ranges from 40-50%, while the incidence rate of positive margins remains 5-40%. A positive margin upon pathologic examination signifies the possibility of tumor extension beyond the boundaries of surgical resection and has been demonstrated to adversely affect disease-free survival. Paulson reported that 10% of patients with negative margins died from malignancy within 13.5 years after surgery, compared with 40% of those with positive surgical margins. Therefore, the presence of a positive margin upon pathologic examination is an unfavorable prognostic indicator, and many men undergoing RP for clinically localized disease may have an unfavorable pathologic outcome. The Partin tables are the best nomogram for predicting prostate cancer spread and prognosis.

For excellent patient education resources, visit eMedicine's Prostate Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education article Prostate Cancer.

NEOADJUVANT ANDROGEN DEPRIVATION

Section 3 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

The high incidence of extracapsular penetration and positive margins following RP in patients with clinically localized prostate cancer is concerning. Therefore, the higher risk of progression associated with these findings has led to efforts to improve preoperative staging and to find ways to facilitate complete tumor excision. Neoadjuvant androgen deprivation (NAD) has been proposed as a method to help down-stage clinically localized or locally advanced prostate carcinoma, with the hope of improving survival. Androgen deprivation induces programmed cell death (apoptosis) and inhibits cell proliferation in malignant prostate tissue.

In 1941, the initial pioneers, Huggins and Hodges, won the Nobel Prize for first demonstrating the effect of androgen withdrawal on benign and malignant prostate tissue. The role of androgen deprivation is now well established in the management of advanced prostatic carcinoma; however, its role preoperatively remains controversial. NAD is a systemic therapy administered after the diagnosis of cancer but prior to locoregional therapy such as RP or radiation. The concept is not new; it was introduced more than a half a century ago by Vallet et al. Subsequently, others have studied this concept in more depth with the hope that NAD may pathologically down-stage the tumor by shrinking the cancer, increasing organ confinement, and decreasing the incidence of positive margins. Neoadjuvant therapy has also been theorized to treat occult regional and systemic micrometastasis, with the ultimate goal being improved long-term, disease-free survival.

In current practice, with the advent of safe and reversible forms of androgen deprivation such as luteinizing hormone-releasing hormone (LHRH) analogues and antiandrogens (AAs), a resurgence in enthusiasm has occurred for NAD therapy. LHRH agonists exert their effects by initial stimulation of the production of luteinizing hormone (LH) at the pituitary, followed by suppression of LH and testosterone to castration levels after approximately 2 weeks. AAs counteract the effects of adrenal androgen at the target cell by interfering with binding at the receptor in a competitive manner. Together, these agents provide powerful androgen blockade (see Table 1).

Table 1. Agents of NAD Therapy

*Liver function tests

†Deep vein thrombosis

MEDICATION

Section 4 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

Drug Category: Androgen deprivation agents

Androgen antagonist used to induce tumor regression.

RATIONALE FOR NEOADJUVANT ANDROGEN DEPRIVATION THERAPY

Section 5 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

RP is most likely to cure patients with organ-confined disease. However, due to the inaccuracy of clinical staging, approximately 50% of men with clinical stage T1 or T2 prostate cancer have tumor extension outside of the prostate capsule and 5-40% have positive margins. Approximately 20-30% of these men with one or more positive margins experience relapse, depending on the site of the positive margin, preoperative PSA level, Gleason score, and presence of seminal vesical invasion. The rationale for the use of NAD prior to RP is to eradicate malignant androgen-dependent cells in the hope that sufficient tumor regression will permit complete resection of residual prostate cancer, improving pathologic outcome and survival.

CLINICAL TRIALS

Section 6 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

Nonrandomized trials (stage T1-T3)

Many nonrandomized trials of NAD therapy have been conducted on patients with clinical stage T1-T3 disease. Fair et al reported a nonrandomized study of 3 months of NAD therapy in 69 patients with T1-T3 prostate cancer, using 72 stage-matched controls. Androgen deprivation consisted of 3 months of an LHRH agonist and flutamide. A pathologic organ-confined rate of 74% was observed in the treatment arm, compared with 48% in the nonpretreated group. The margin-positive rate was 10% in the NAD group versus 33% in patients without induction of androgen deprivation. The PSA disease-free rate at a mean follow-up of 28.6 months was 89% in pretreated patients and 84% in controls. No significant difference occurred with respect to biochemical failure.

Meyer et al from Laval University in Quebec, Canada recently published their report of 38 months of follow-up of 680 patients, 292 of whom received NAD prior to radical retropubic prostatectomy. Surgical margins were positive less often in the NAD group (25%) than in the prostatectomy-alone group (47%). PSA failure (>0.3 ng/mL) was observed in 163 patients, and the 5-year failure rate was 33%. Patients treated with neoadjuvant hormonal therapy had significantly lower hemoglobin and hematocrit levels before surgery and, therefore, required blood transfusion more often. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with RP alone, suggesting a possible benefit of improved disease-free survival.

The University of Miami conducted one of the largest nonrandomized retrospective reviews. Of 546 consecutive patients undergoing RP, 135 received NAD for a median duration of 3 months prior to surgery. In an effort to create 2 comparable groups among those who did and did not receive NAD therapy, only patients with a PSA value greater than 10 ng/mL and/or biopsy Gleason score greater than 7 and/or stage greater than cT2b were included in the analysis. The impact of NAD on pathological outcome and disease recurrence was assessed for a mean follow-up of 26 months.

Patients with NAD were found to be less likely to have positive margins (28% vs 38%, P = .10). However, the incidence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis was not different between the 2 groups. The recurrence rate was 17% in nontreated patients and 25% in NAD-treated patients (P = .07). Even though a decrease in the incidence of positive surgical margins was observed, the difference did not translate into improved disease-free survival at 26 months of follow-up.

In summary, for patients with stage T1-T3 disease who were treated preoperatively with androgen deprivation, the most consistent findings were a 30-50% decrease in prostate volume and an approximate 90% decline in serum PSA values. Also observed was an improvement in organ-confined disease and margin status, without a therapeutic effect on seminal vesicle or lymph node involvement. Few of these studies documented long-term follow-up. In studies documenting long-term follow-up, no statistically significant difference in disease-free survival occurred.

Table 2. Nonrandomized Trials of NAD Therapy

*Total androgen blockade

†Diethylstilbestrol

RANDOMIZED CLINICAL TRIALS

Section 7 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

Prospective randomized trials

Labrie et al published the first prospective randomized trial in 1993. One hundred sixty-one men with stage B0-C2 cancer were randomized to surgery alone or 3 months of NAD (LHRH and flutamide) therapy followed by RP. They reported significant clinical and pathologic down-staging and a decreased incidence of positive margins, seminal vesicle invasion, and lymph node metastasis in the NAD group. No follow-up was reported (see Table 3).

Table 3. Randomized Clinical Trials of NAD Therapy

Soloway et al conducted a randomized multicenter T2bN0M0 trial (1995). Three hundred and three patients were enrolled in the study and randomized to RP plus NAD with an LHRH agonist and flutamide (149 patients) or surgery alone. Patients who received androgen deprivation preoperatively had a significantly lower rate of capsule penetration (47% vs 78%, P <.001), positive surgical margins (18% vs 48%, P <.001), and tumor at the urethral margin (6% vs 17%, P <.01). Androgen deprivation did not affect seminal vesicle invasion or lymph node metastasis. Prostate volume decreased by 30%, and the PSA level decreased to less that 1 ng/mL in 88% of patients and to less than 2 ng/mL overall. Upon pathologic examination, no evidence of tumor (pT0) was found in 6 (4%) patients treated with NAD. At 42 months of follow-up, no significant difference in recurrence (25%) was noted between the 2 groups.

In 1996, the Canadian Urologic Oncology Group (CUOG) published the results of a randomized study on 213 patients, of which 112 were treated with 12 weeks of cyproterone acetate at 300 mg/d prior to surgical therapy. Both groups were well balanced at baseline in terms of demographics, clinical stage, Gleason score, PSA value, and prostate size. The volume of the prostate gland determined by TRUS findings decreased by 20%. The incidence of positive margins was also decreased in the NAD-treated group (27.7% vs 64.8%). No tumors were down-staged to pT0. Goldenberg et al concluded that NAD therapy significantly decreased the incidence of positive margins; however, at 36 months of follow-up, no difference was noted in the biochemical recurrence rate.

In 1997, Witjes et al (European Study Group on Neoadjuvant Treatment of Prostate Cancer) published a large randomized trial that included 354 patients, of whom 164 were treated with NAD (goserelin acetate plus flutamide) for 3 months. Serum PSA levels decreased by more than 90% in the NAD-pretreated group. Pathologic down-staging was observed in 16% of the NAD group and 6% in the surgery-alone group (P <.001). In patients with clinical T2 tumors, a significant difference in positive margins was demonstrated in favor of patients receiving neoadjuvant therapy. In patients with clinical T3 tumors, no significant difference in margin status occurred. At 15 months of follow-up of 215 patients, the progression-free survival rate did not differ between the 2 groups. Researchers concluded that neoadjuvant therapy was investigational and not advised outside of randomized clinical trials.

Summary of the clinical effects of NAD therapy

Neoadjuvant therapy has distinct clinical effects in patients with prostate cancer.

With regard to serum PSA levels, most of the clinical trials have demonstrated a decrease in levels of approximately 90% with 3 months of androgen deprivation. PSA values decline most rapidly over the first 1-2 months. PSA nadir is reached in 22-34% of patients after 3 months of NAD therapy and in 84-86% after 8 months. Time to nadir does not seem to be related to the pretreatment PSA value. Undetectable PSA is achieved in 27-55% of patients after 3 months of NAD and in 66-73% at 8 months. However, changes in the serum PSA level do not always reflect changing tumor burden accurately, and, therefore, the PSA value is not a good clinical indicator of disease.

With regard to prostate size, prostate volume is decreased by approximately 30% after 3 months of NAD. This reduction is the result of apoptosis and atrophy of both benign and malignant cells. Extending the period of NAD to 8 months results in a significantly greater reduction in prostate volume.

For clinical stage, NAD produces clinical down-staging in approximately 40% of men with cT1-T2 tumors and in 32-90% of men with cT2-T3 tumors.

PATHOLOGIC CHANGES OF NEOADJUVANT ANDROGEN DEPRIVATION

Section 8 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

Androgen deprivation therapy produces distinct histopathologic changes in both neoplastic and nonneoplastic prostate tissue. A pathologist not familiar with these alterations may misinterpret the specimen, resulting in inappropriate tumor grading or missed tumor foci; thus, the urologist should convey to the pathologist any information regarding therapy that might cause histopathologic changes.

Civantos et al published the largest series in 1995. They reviewed a series of 173 patients who were treated with an LHRH analogue and an AA prior to RP. Atrophy was observed in both benign and malignant tissue. Examination of noncancerous tissue revealed atrophy of secretory cells, with cytoplasmic clearing and vacuolization. Atrophy and disappearance of luminal cells resulted in basal cell prominence. Morphologic alterations induced by treatment were patchy; the entire neoplastic tissue was affected in only 57% of the specimens. The poorly differentiated areas of tumors were affected less frequently.

Three types of changes in neoplastic tissue were reported. In the most common pattern (90%), the size of the neoplastic glands was reduced. An increase in stroma with a resultant relative decrease in gland density accompanied the size reduction.

Branching empty spaces lined by a few remaining cancer cells with pyknotic nuclei and foamy vacuolated cytoplasm characterized the second pattern (20%). The third pattern (10%) consisted of large, clear, or vacuolated tumor cells within an inflammatory background. The incidence of high-grade prostatic intraepithelial neoplasia was less common in the prostate specimens from patients treated with neoadjuvant therapy.

Pathologic implications of NAD therapy

With regard to surgical margins, clinical trials have demonstrated that NAD significantly reduces the rate of positive margins, due to either tumor regression or the improved ability to resect the prostate with wider surgical margins. The interpretation of margin status on RP specimens after NAD has been the source of much debate. However, with the use of consistent step-sectioning and special stains, the authors believe that an experienced uropathologist can differentiate a true positive margin accurately.

The effectiveness of NAD in reducing positive surgical margins depends on clinical tumor stage and the biopsy Gleason score. NAD has been demonstrated to decrease positive margins significantly in clinical stage T1 and T2 prostate cancer but not in clinical stage T3 cancer. Men with cT3 disease or Gleason score greater than 7 have a less dramatic reduction in positive margins, implying that higher-grade tumors may be less responsive to androgen deprivation therapy. Therefore, men with clinical stage T3 and a Gleason score greater than 7 are at a high risk of positive margins despite 3 months of NAD therapy; the authors await the results of the CUOG 3-month versus 8-month therapy trial to determine whether 8 months is more beneficial.

Two of the Gleason criteria are altered by neoadjuvant therapy. A decrease in gland size and an increase in stroma between glands occur. These findings can lead to a false upgrade of the Gleason score. The use of a modified Gleason system has been proposed to evaluate prostatectomy specimens from patients who have received NAD; some physicians have suggested that no Gleason score should be allocated.

When considering pelvic lymph node metastasis, most studies reveal no significant difference in the incidence of pelvic lymph node metastasis. Therefore, NAD therapy does not appear to affect pelvic lymph node metastasis.

With regard to seminal vesical invasion, NAD does not appear to have an effect.

SURGICAL IMPLICATIONS OF NEOADJUVANT THERAPY

Section 9 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

NAD has been demonstrated to decrease prostate volume by 20-50%. The initial hope was that shrinking the gland would make RP technically easier, with less blood loss. The findings have been inconsistent.

In the multicenter randomized T2bN0M0 trial, the surgeons rated the difficulty of dissection, presence of seminal vesicle adherence, and extent of blood loss. They also recorded the operating time and amount of blood transfused. Seminal vesicle adherence to the periprostatic tissues was more common in patients pretreated with NAD (37%) compared with those treated with surgery alone (21%). Surgical dissection was more difficult in pretreated patients. No significant difference in operating time, blood loss, or transfusion requirement occurred. Although more dissections that were difficult were reported with NAD therapy, no operative complications occurred in the NAD-treated group, whereas 6 intraoperative injuries were reported in patients undergoing surgery alone.

In cases of patients with large prostates, NAD therapy may facilitate resection by reducing prostate volume, creating more space for the surgeon to operate. However, in patients with smaller prostates, NAD may have a less-desirable effect by allowing the prostate to recede further under the pubic bone, complicating exposure during the apical dissection. The periprostatic fibrous reaction is variable and may increase the difficulty of surgery, particularly at the apex and seminal vesicles. The authors believe that apical dissection is potentially the most difficult problem caused by NAD. Of serious concern is the fact that NAD-induced fibrosis can make intraoperative evaluation of the extent of the tumor more difficult, which can possibly compromise the extent of resection if the surgeon relies on intraoperative findings to determine performance of a nerve-sparing operation.

Duration of NAD treatment

The optimal duration of NAD prior to RP is unknown. Most trials have arbitrarily used 3 months of therapy. However, Gleave et al suggest that a longer course of preoperative therapy is necessary. They attribute the initial dramatic fall in PSA from androgen ablation to the cessation of androgen-regulated PSA gene expression, whereas a continuing gradual decline represents the actual decrease in tumor volume. They treated patients for 8 months. The mean PSA level decreased 84% after 1 month, and a further decrease of 52% was observed from 3-8 months. Twenty-two percent of patients reached their PSA nadir at 3 months and 84% after 8 months. Therefore, Gleave et al advocate 8 months as the optimal duration of treatment. No long-term follow-up results have been reported.

Disadvantages of NAD prior to RP

• Clinical trials have not demonstrated improvement in disease-free survival rates.
• NAD has an unknown therapeutic effect on microscopic local or metastatic disease.
• Poorly differentiated areas of tumor are altered minimally.
• Tumor is rarely completely eradicated (pT0).
• Risk of androgen-independent clonal proliferation exists with prolonged NAD therapy.
• Compromising the evaluation of extent of the tumor at surgical resection is possible.
• Pathologic interpretation may be obscured.
• Increased difficulty occurs at surgery due to periprostatic fibrosis.
• Cost of therapy is a disadvantage.
• Adverse effects are a potential disadvantage.
• Treatment of the tumor is delayed.
• Chance of blood transfusion during surgery is increased.

Advantages of NAD prior to RP

• Rate of positive margins is reduced.
• Organ-confined disease is increased.
• Serum PSA level is reduced.
• Prostate size is reduced.

CONCLUSION

Section 10 of 11  

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

A surgical cure for prostate cancer can be expected only if the entire tumor is excised. Of men with clinical stage T1 or T2 prostate cancer, 50% have tumor extension outside the prostatic capsule and 5-40% have positive margins. Some of these patients have incompletely resected cancer and, therefore, are at an increased risk for local recurrence and progression. The concern over cancer progression has led to a renewed interest in the use of NAD therapy prior to RP. The goal is to shrink the tumor in an effort to increase organ confinement and reduce the risk of positive margins, improving disease-free survival.

Most trials have used 3 months of neoadjuvant therapy and have demonstrated a significant decrease in prostate volume by 20-50% and serum PSA levels by more than 90%. Studies have also reported a significant increase in organ-confined disease and a decrease in the incidence of positive margins. However, to date, no randomized or nonrandomized study using 3 months of neoadjuvant therapy has shown any statistically significant benefit in terms of reduced PSA failure or an improved disease-free survival.

While the evidence suggests that 3 months of androgen deprivation therapy is not sufficient, current evidence indicates that increasing the duration of therapy to 6 or 8 months further reduces tumor volume and PSA nadir levels and decreases the proportion of men with positive margins. A randomized trial is being conducted to compare disease-specific survival in prostate cancer cases treated with RP following NAD therapy for 8 or 3 months, but data on PSA failure are not yet available. Preliminary results indicate that prolonged therapy may be beneficial. A subset of patients is likely to benefit from neoadjuvant therapy; this population of patients is yet to be defined and may become clearer as the optimal duration and form of NAD therapy is defined.

Gleave et al have proposed 8 months of therapy as the preferred duration of treatment, using PSA nadir as a marker for disease response. However, serum PSA values may not be an accurate surrogate marker for response to treatment. Serum PSA levels after hormonal treatment do not reflect the actual tumor burden. Thus, the rate of early PSA failure may be a difficult end-point to interpret after hormonal pretreatment because the PSA level is decreased by hormonal treatment. Therefore, assessing the true clinical effect of hormonal pretreatment may be difficult with commonly used surrogate end-points, such as the presence or absence of positive surgical margins or serum PSA level.

Androgen-independent cells have been demonstrated to be present in the earliest stages of prostate cancer in all parts of the prostate, and these cells are refractory to therapy. Androgen-independent cells have also been demonstrated to be present in microscopic foci of metastatic disease. NAD has been demonstrated to be less effective against high-grade tumors, often leaving such areas unaltered. Therefore, no reason exists to assume that these types of cells are not present in micrometastatic disease or that they will be eradicated when the tumor becomes confined to the prostate after androgen deprivation therapy. The cost of therapy and the possibility of the proliferation of androgen-independent cells during the androgen deprivation period must also be considered.

Many unanswered questions exist regarding the benefit of NAD therapy. Several randomized and nonrandomized trials with as many as 7 years of follow-up have been conducted and have failed to demonstrate any benefit of neoadjuvant therapy in terms of disease progression or survival. A recent review of the existing literature suggests that NAD before RP is neither indicated nor justified and should currently be considered for use only in controlled clinical trials.

Prolonged NAD may provide the answer; however, until the benefit of prolonged NAD is assessed, other alternative treatments must be explored. The combination of androgen deprivation with cytotoxic chemotherapy in patients with adverse prognostic factors who elect to undergo RP may improve the future of neoadjuvant therapy.

While a trend in favor of treating patients using more than 3 months of neoadjuvant androgen therapy prior to RP appears to exist, no studies have reached statistical significance. Currently, data are insufficient to support the routine recommendation of NAD therapy. Until this ambiguity is clarified, the utility of NAD prior to RP will remain controversial. The ultimate benefit of any therapy will be determined only through properly designed trials with long-term follow-up.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Neoadjuvant Androgen Deprivation
• Medication
• Rationale for Neoadjuvant Androgen Deprivation Therapy
• Clinical Trials
• Randomized Clinical Trials
• Pathologic Changes of Neoadjuvant Androgen Deprivation
• Surgical Implications of Neoadjuvant Therapy
• Conclusion
• References

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