Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer

PURPOSE: We evaluated patients at our institution who underwent radical prostatectomy for clinical stage T3 prostate cancer to determine their long-term clinical outcomes. MATERIALS AND METHODS: We reviewed our prospective surgical database and identified 176 men who underwent radical retropubic prostatectomy for clinical stage T3 prostate cancer from 1983 to 2003. Clinical and pathological data were reviewed and evaluated in a Cox proportional hazards model to determine preoperative predictors of biochemical recurrence. Clinical progression following biochemical recurrence was evaluated and clinical failure was defined as the development of clinical metastases or progression to hormone refractory prostate cancer. RESULTS: Of the 176 patients with cT3 prostate cancer 64 (36%) received neoadjuvant hormonal therapy. At a mean followup of 6.4 years 84 (48%) patients had disease recurrence with a median time to biochemical recurrence of 4.6 years. The actuarial 10-year probability of freedom from recurrence was 44%. On multivariate analysis biopsy Gleason score, pretreatment serum prostate specific antigen and year of surgery were independent predictors of biochemical recurrence. Neoadjuvant hormonal therapy was not a significant predictor of biochemical recurrence. Following biochemical recurrence clinical failure developed in 30 of 84 (36%) men with a median time of 11 years. Overall the 5, 10 and 15-year probabilities of death from prostate cancer were 6%, 15% and 24%, respectively. CONCLUSIONS: More than half (52%) of our patients remained free of disease recurrence following radical prostatectomy. In our series neoadjuvant hormonal therapy offered no advantage with respect to disease recurrence. Radical prostatectomy remains an integral component in the treatment of select patients with clinical stage T3 prostate cancer.     

Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure

PURPOSE: To date there is little information on the long-term effect of neoadjuvant hormonal therapy on prostate cancer progression. We performed a prospective study to determine whether patients with prostate cancer receiving neoadjuvant hormonal therapy before radical prostatectomy (hormonal therapy group) have a lower risk of prostate specific antigen (PSA) failure than those treated with radical prostatectomy alone (prostatectomy group). We also evaluated whether type of neoadjuvant hormonal therapy and duration were associated with the risk of PSA failure. MATERIALS AND METHODS: We followed 680 men initially treated for prostate cancer with radical prostatectomy between January 1988 and December 1997 at our university hospital. Of the patients 292 received neoadjuvant hormonal therapy. Median followup was 38 months. Cox regression analysis was used to assess the association between neoadjuvant hormonal therapy and PSA failure (greater than 0.3 ng./ml.) controlling for age, clinical stage, grade, initial PSA and adjuvant therapies. RESULTS: Surgical margins were positive less often in the hormonal therapy (25%) than the prostatectomy (47%) group (p = 0.0001). PSA failure was observed in 163 patients and the 5-year failure rate was 33%. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups (hazards ratio 0.94, 95% confidence interval 0.68 to 1.30). Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). CONCLUSIONS: Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy.     

25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series

PURPOSE: We report on 25-year cancer control and survival outcomes after radical prostatectomy in a single center series of patients treated during a 40-year period. MATERIALS AND METHODS: Between 1954 and 1994, 787 consecutive patients underwent radical prostatectomy at Virginia Mason Medical Center in Seattle, Washington. Kaplan-Meier 25-year probabilities of prostate cancer specific, overall, prostate specific antigen progression-free, local and distant progression-free survival were determined. Multivariate Cox regression models addressed prostate cancer specific mortality. RESULTS: Prostate cancer specific survival, overall survival, prostate specific antigen progression-free survival, local and distant progression-free survival ranged from 99.0% to 81.5%, 93.5% to 19.3%, 84.8% to 54.5%, 95.3% to 87.8% and 95.9% to 78.2%, respectively. In univariate analyses pathological stage, surgical margin status, pathological Gleason sum, delivery of hormonal therapy and radiotherapy represented statistically significant predictors of prostate cancer specific mortality (all p < or =0.001). In multivariate analyses only Gleason sum (p = 0.03) and delivery of hormonal therapy (p < 0.001) remained significant. CONCLUSIONS: This is one of the most mature radical prostatectomy series. It demonstrates that long-term biochemical cancer control outcomes after radical prostatectomy might be suboptimal. However, local and distant control outcomes are excellent, and cancer specific mortality is minimal even 25 years after surgery.     

Clinicopathological significance of neoadjuvant hormonal therapy prior to radical prostatectomy: whole section analysis

We investigated whether the histopathological effect (cell viability) of neoadjuvant hormonal treatment before radical prostatectomy for clinically localized prostate cancer is involved in the biochemical outcome, i.e., androgen independency. Non-randomized prospective trial was carried out between September 1996 and April 2001 involving the patients with clinical stage T1-3 prostate cancer, including 62 who underwent radical prostatectomy after receiving neoadjuvant hormonal treatment for an average of 6.3 months and 76 who underwent radical prostectomy only. All resected specimens were histopathologically diagnosed by whole section analysis. The patients receiving neoadjuvant hormonal treatment were categorized into 4 groups according to the histological change in the resected prostate. There were 8 patients in G0 (all viable cells), 11 patients in G1 (more than 50% viable cells), 26 patients G2 (more than 50% non-viable cells) and 17 patients in G3 (no cancer cells). No difference in the patient background (prostate specific antigen, stage, Gleason score, positive core Nr, duration of neoadjuvant therapy) was observed in any group, except for the duration of (p < 0.05). Multivariate hazards analyses revealed that only the duration of neoadjuvant hormonal treatment was independently associated with excellent responders with grade 3 histological effect. Neoadjuvant hormonal therapy prior to radical operation resulted in various histopathological changes in the prostate, but it is not clear whether the histological effects of hormonal treatment might be involved in the outcome. A longer follow-up randomized prospective trial is necessary.     

Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables.

PURPOSE: We evaluated the long-term outcome of radical prostatectomy for pathological Gleason score 8 or greater prostate cancer and characterized the prognostic significance of other pathological variables. MATERIALS AND METHODS: A total of 6,419 patients underwent radical prostatectomy between 1987 and 1996. There were 407 patients classified as having pathological Gleason 8 or greater, including 8 in 48%, 9 in 49% and 10 in 3%. Adjuvant treatment was used in 45% of patients and adjuvant hormonal therapy was administered to 155 (38%). Progression-free, including local or systemic, and/or prostate specific antigen (PSA) 0.4 ng./ml. or greater, and cancer specific survival were determined by the Kaplan-Meier method. The effect of pathological grade and stage, preoperative PSA, DNA ploidy, margin status, tumor dimension, seminal vesicle invasion, and adjuvant treatment was assessed with the univariate and multivariate analyses. RESULTS: Pathological stage distribution was pT2 in 26% of patients, pT3 48% and pTxN+ 27%. Overall and progression-free survival at 10 years was 67% and 36%, respectively, compared to cancer specific survival 85%. Adjuvant treatment, pathological stage, preoperative PSA and pathological grade were significant (less than 0.05) univariate predictors of progression-free survival. Pathological stage, margin status and ploidy were univariately associated with cancer specific survival. Progression-free survival at 10 years of those patients who did and did not receive adjuvant treatment was 52% and 23%, respectively. In the multivariate analysis pathological grade (p=0.02), preoperative PSA (p <0.0001), adjuvant therapy (p <0.0001) and pathological stage (p=0.036) were significant independent predictors of progression-free survival. CONCLUSIONS: High grade prostate cancer can be controlled with radical prostatectomy in some patients with disease confined pathologically, and 10-year cause specific survival is 96%. Predictors of outcome in patients with Gleason 8 disease or greater are similar to established predictors derived by using all grades. Although adjuvant hormonal therapy appears to improve disease progression rates after radical prostatectomy on the basis of this nonrandomized study, it may not affect prostate cancer death rates within 10 years in patients with high grade cancer.     

Induction androgen deprivation plus prostatectomy for stage T3 disease: Failure to achieve prostate-specific antigen-based freedom from disease status in a phase II trial

Objectives

There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations.

Methods

Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide ± flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections.

Results

Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%.

Conclusions

Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NHT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.     

Neoadjuvant hormonal therapy and radical prostatectomy in the treatment of clinical stage T3 cancer of the prostate

We evaluated the results of a treatment protocol that consisted of neoadjuvant hormonal therapy followed by radical retropubic prostatectomy (RRP) for clinical stage T3 (cT3) prostate cancer. Sixty-six patients with cT3 prostate cancer underwent staging procedures that included metastatic work-up and evaluation under anesthesia. Neoadjuvant hormonal treatment was given for 3 to 6 months, followed by re-evaluation under anesthesia. Patients considered to have a resectable prostate following neoadjuvant treatment underwent operation. Disease-free survival [prostate-specific antigen (PSA) < 0.1 ng/ml] was calculated by the Kaplan-Meier method for cT3 patients and for a group of patients with clinical stage 1 and 2 disease (cT1-2), who underwent RRP without neoadjuvant hormonal therapy. Patients with pT3 disease in both groups received early adjuvant radiation treatment. Patients in the cT3 group who were not clinically downstaged were treated with radiation. Patients with positive lymph nodes continued hormonal therapy. The pretreatment PSA for the cT3 group was 43.6 ± 55.6 ng/ml, and 10.64 ± 7.18 ng/ml for the cT1-2 group (p < 0.05). Of 66 cT3 patients, 53 (80%) were clinically downstaged and operated on and 47 (71%) underwent RRP. At 36 months, there was no significant difference in the PSA relapse rate between these two groups; both had significantly lower rates than did patients in the cT3 without RRP. At 48 months, 79% (21 patients) of the patients in the cT3-RRP group were disease free compared with 50% of those in the cT3 without RRP (4 patients). Neoadjuvant hormonal therapy for stage cT3 prostate cancer selects patients whose cancer can be controlled by RRP for an extended period of time.     

The perioperative charge equivalence of interstitial brachytherapy and radical prostatectomy with 1-year followup

PURPOSE: We compare the comprehensive 1-year charges in a consecutive group of patients undergoing radical prostatectomy and transperineal interstitial brachytherapy for clinically localized prostate cancer at a single urban institution. MATERIALS AND METHODS: A total of 60 consecutive men with clinically localized prostate cancer (T1-T2, N0, M0) were treated during a 15-month period with radical prostatectomy or interstitial brachytherapy. Hospital and outpatient records were analyzed for each patient in regard to preoperative, operative and postoperative charges. Parameters included number of encounters, diagnostic and therapeutic interventions, hospitalization and operative charges, and followup visits, diagnostic tests and interventions for 1 year. All charge calculations were based arbitrarily on the 1996 Medicare fee schedule, factoring in the mandated global charge reimbursement period of 90 days for both procedures. RESULTS: Of the patients 38 underwent radical prostatectomy (prostatectomy group) and 22 underwent interstitial brachytherapy (brachytherapy group). The brachytherapy group was older with higher pretreatment serum prostate specific antigen and clinical stage disease, and more frequently received neoadjuvant hormonal therapy compared to the prostatectomy group. The 2 groups were similar in Gleason score and, when applicable, duration of neoadjuvant hormonal therapy. Preoperative charges were 15.3% lower for prostatectomy than for brachytherapy (not statistically significant). Conversely, operative charges for prostatectomy were 13.5% higher (p = 0.04). The major difference among preoperative, operative and postoperative charges was for those incurred postoperatively by the brachytherapy group, which were 56.0% higher than those for the prostatectomy group ($2,285.20 versus $1,007.20, p = 0.0004). CONCLUSIONS: Transperineal interstitial seed implantation is perceived by many as more cost-effective than radical prostatectomy for patients with clinically localized prostate cancer. We demonstrated that when such patients were followed for 1 year, the comprehensive charges for radical prostatectomy and interstitial brachytherapy were equivalent.     

Neoadjuvant docetaxel/estramustine prior to radical prostatectomy or external beam radiotherapy in high risk localized prostate cancer: A phase II trial

Background

Patients with locally advanced or organ confined, high risk, prostate cancer are at significant risk of having disease recurrence despite definitive local therapy. We evaluated the 2-year progression-free survival of subjects treated with chemotherapy administered prior to definitive therapy with surgery or radiation.

Patients and methods

Patients (n = 24) with locally advanced and high risk localized prostate cancer were treated with neoadjuvant docetaxel 36 mg/m2 i.v. weekly for 3 weeks and estramustine 140 mg orally 3 times daily for 3 consecutive days every 28 days prior to definitive treatment with prostatectomy or radiation.

Results

All evaluable patients, except 1, completed the proposed cycles of neoadjuvant chemotherapy with minimal dose reductions or delays. Of the 22 evaluable patients, 12 underwent radical prostatectomy and 10 underwent external beam radiation therapy. Twenty-one of 22 patients achieved a prostate-specific antigen (PSA) reduction > 25%. There were no pathologic complete responses. With a median follow-up of 24 months, the 2-year progression-free survival was 45%.

Conclusions

Our findings support the safety, tolerability, and efficacy of neoadjuvant chemotherapy in patients with men with high risk, locally advanced prostate adenocarcinoma, although the relative contributions of androgen deprivation therapy and docetaxel cannot be determined. The effectiveness of neoadjuvant chemotherapy in preventing prostate cancer relapses should be studied in a randomized trial.     

Clinical study of radical retropubic prostatectomy for prostate cancer]

PURPOSE: To evaluate the results of radical retropubic prostatectomy in patients treated at a single institution. MATERIALS AND METHODS: Between April 1985 and July 1997, 76 patients with prostate cancer underwent radical retropubic prostatectomy, including 73 receiving pelvic lymphadenectomy. The median age and follow-up time were 68 years old and 44 months, respectively. The pathological stage was pT0 in 6 patients, pT2 in 29, pT3 in 39, pT4 in 2, and pN+ in 22. RESULTS: The surgical margin was positive in 10% of the pT2 patients and 61% of the pT3 patients. Twelve patients had recurrence. Recurrence was shown by biological failure in 4 patients and clinical failure in 8. The disease-free 5-year survival rates (Kaplan-Meier) were 100% in pT0 patients, 87% in pT2, 72% in pT3, 50% in pT4, 77% in pN-, 75% in pN+, 73% for a positive surgical-margin, and 83% for a negative surgical-margin. There were no statistical differences between any of these factors. However, the disease-free survival rate in pT3 patients with poorly differentiated adenocarcinoma (PDA) who received postoperative radiotherapy combined with hormonal therapy was significantly superior to that in patients with the same characteristics who received hormonal therapy (100% vs 27%; p = 0.011). The cause-specific 5-year survival rates were 100% in pT0, 100% in pT2, 92% in pT3, 50% in pT4, 94% in pN-, 93% in pN+, 93% for a positive surgical-margin, 98% for a negative surgical-margin, 100% in the aforementioned pT3 patients with PDA and postoperative radiotherapy combined with hormonal therapy and 86% in pT3 patients with PDA and postoperative hormonal therapy. There were no statistical differences between any of these factors. CONCLUSIONS: Our results suggest that radical prostatectomy is available for both organ-confined and non organ-confined advanced prostate cancer. Postoperative radiotherapy combined with hormonal therapy is especially useful for patients in pT3 with PDA.     

Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial

OBJECTIVE: To describe the outcome, assessed as the level of prostate specific antigen (PSA), of a mature (more than half the events recorded) prospective randomized study with a median follow-up of 82 months of neoadjuvant hormonal therapy before radical prostatectomy, as this has been suggested to decrease the rate of positive surgical margins (i.e. provide greater potential to completely excise the tumour). PATIENTS AND METHODS: From December 1991 to March 1994, 126 patients with clinically localized prostate cancer were randomized between direct radical prostatectomy or a 3-month course of a gonadotrophin-releasing hormone analogue before surgery. The patients were followed by PSA determinations and a value of > 0.5 ng/mL used to define progression. RESULTS: The incidence of positive surgical margins decreased from 45.5% to 23.6% (P = 0.016) with hormone treatment. Despite this there was no difference in PSA progression-free survival at the last follow-up; it was 51.5% for those undergoing radical prostatectomy only and 49.8% for those who received hormonal pretreatment (P = 0.588). CONCLUSIONS: Three months of neoadjuvant hormonal therapy before radical prostatectomy offers no benefit to the patient and cannot be recommended for routine clinical use.     

A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up

OBJECTIVE: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer. PATIENTS AND METHODS: Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years. RESULTS: The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively. CONCLUSION: The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.     

Treatment results of radical prostatectomy in clinical stage B and C prostate cancer: comparison of the neoadjuvant therapy group versus the surgery group; retrospective analysis of 80 cases

Between 1994 and 2001, 80 patients underwent radical prostatectomy without adjuvant therapy for clinical stage B and C prostate cancer. The patients were not treated with adjuvant therapy before biochemical prostate specific antigen (PSA) failure. Of all 80 patients, 35 patients (43.8%) received neoadjuvant hormonal therapy prior to radical prostatectomy (the neoadjuvant therapy group), 45 patients (56.2%) underwent prostatectomy alone (the surgery alone group). Retrospective analysis to evaluate the effects of neoadjuvant therapy was performed from clinicopathological findings and the biochemical PSA failure-free rate. Of all patients, 58 (72.5%) were in clinical stage B and 22 (27.5%) were in clinical stage C. Of 58 patients in clinical stage B, 19 (32.8%) underwent prostatectomy combined with neoadjuvant therapy. Of the 22 patients in clinical stage C, 17 (77.3%) underwent prostatectomy combined with neoadjuvant therapy. Pathologically, 37 (46.3%) were in stage B, 38 (47.5%) in stage C and 2 (2.5%) in stage D1. Three patients in the neoadjuvant therapy group had no malignant findings in specimens of prostatectomy. In comparison with the clinical stage, pathologically 8 (22.9%) showed overstaging, 4 (5.0%) understaging and 23 (28.8%) accurate staging in the neoadjuvant therapy group, respectively, 0 (0.0%), 20 (44.4%), and 25 (55.6%) in the surgery alone group. In clinical stage B and C, there was no significant difference in the biochemical PSA failure-free rate between the neoadjuvant therapy group and the surgery alone group. On the other hand, in pathological stages B, the 5-year PSA failure-free rate was 63.2% in the neoadjuvant therapy group, but 100% in the surgery alone group. Although neoadjuvant therapy may have some effect on downstaging, our retrospective analysis suggests that it has no significant effect on PSA failure-free rate.     

Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.     

Radical prostatectomy can provide a cure for well-selected clinical stage T3 prostate cancer

OBJECTIVE: Radical prostatectomy is commonly believed not to achieve the eradication of locally advanced disease. This retrospective study aimed to elucidate the role of radical prostatectomy in this condition. METHODS: A retrospective study of 158 patients surgically treated for clinical stage T3N0M0 prostate cancer was undertaken. Thirty patients had postoperative hormonal treatment, rendering prostate-specific antigen (PSA) follow-up unreliable, and were considered to be progressive at 1 month. Eighteen other patients received postoperative radiotherapy. One hundred and ten patients had radical prostatectomy only. PSA-relapse-free survival was analyzed. The mean follow-up time was 30 months. RESULTS: Seventy-nine percent of the resected specimens were pathologically T3 (pT3), and about 25% were pT3c. Thirteen percent were pT2 and 8% were pT4. Ninety-five specimens (60%) had positive surgical margins. There was poor accordance between the biopsy Gleason score and that of the specimen. A multivariate analysis showed that seminal vesicle and nodal invasion, margin status and a PSA level above 10 ng/ml were independent prognostic factors. In 47 cT3a patients with PSA <10 ng/ml, the PSA-free survival rate exceeded 70% at 24 months and the 5-year estimated PSA-free survival rate was more than 60%. CONCLUSIONS: Radical prostatectomy has a place in the treatment of clinical stage T3 prostate cancer patients with a PSA value lower than 10 ng/ml. There is a need to definitively rule out nodal or seminal vesicle invasion in order to select those patients that can benefit from surgery.     

Survival results in patients with screen-detected prostate cancer versus physician-referred patients treated with radical prostatectomy: early results

OBJECTIVE: Screening using a standardized protocol may improve outcomes of patients undergoing treatment for prostate cancer. We compared the 7- year progression-free survival rates after radical retropubic prostatectomy in patients whose prostate cancer was detected through a formal screening program with those of patients referred for treatment by other physicians who did not use a standardized screening/referral protocol. METHODS: A single surgeon (W.J.C.) performed radical retropubic prostatectomy in 3,177 consecutive patients between 1989 and 2003. Of these patients, 464 had cancer detected in a screening study, and 2,713 were referred from outside institutions. We compared the screened and referred cohorts for age at surgery, clinical stage, pathologic stage, Gleason sum, preoperative prostate-specific antigen (PSA) levels, and adjuvant radiation therapy. Kaplan-Meier product limit estimates were used to calculate 7-year progression-free probabilities, and Cox proportional hazards models were used to determine the clinical and pathologic parameters associated with cancer progression in each group. RESULTS: The overall 7-year progression-free survival rates were 83% for the screened patients compared with 77% for the referred patients (P = 0.002). Preoperative PSA, Gleason sum, clinical stage, pathologic stage, and adjuvant radiotherapy were all significantly associated with cancer progression. There was a significantly higher proportion of referred patients with a preoperative PSA > or =10, Gleason sum > or =7, and nonorgan-confined disease. CONCLUSIONS: Patients with screened-detected prostate cancer have more favorable clinical and pathologic features, and 7-year progression-free survival rates than referred patients. On multivariate analysis, including other clinical variables, screening status was a significant independent predictor of biochemical outcome.     

ROLE OF EARLY ADJUVANT HORMONAL THERAPY AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER

PURPOSE: Recent prospective randomized studies have shown that adjuvant hormonal therapy combined with local treatment can significantly improve overall survival in patients with locally advanced disease. This finding challenges the previous belief that adjuvant hormonal therapy may not be beneficial for minimal stages TxN + M0 or less prostate cancer, particularly when combined with local treatment. We reviewed the benefits of adjuvant hormonal therapy in patients at risk for disease progression, especially when administered after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the current literature and evaluated clinical information on stage pT3b cancer from a large single institution prostate cancer database to determine the current role of adjuvant hormonal therapy after radical prostatectomy for prostate cancer. RESULTS: Retrospective experimental and clinical studies have proved the impact of adjuvant hormonal therapy for decreasing prostate specific antigen (PSA) and clinical disease progression in patients with regionally limited prostatic cancer. This finding applies to stage pT3b as well as to lymph node positive cancer. Our literature review and current data from the Mayo Clinic database show that adjuvant hormonal therapy after prostatectomy has a significant impact on prostate specific antigen (PSA) progression but it also decreases systemic progression and cause specific death in patients with stage pT3b and lymph node positive disease. After adjusting for preoperative PSA, margins, grade, ploidy and patient age the risk ratio for stage pT3b disease in 707 cases was 0.3 (95% confidence interval 0.2 to 0.7). A recent prospective randomized trial showed a significant decrease in cancer death in N+ cases when adjuvant hormonal therapy was administered after radical prostatectomy, supporting previous Mayo Clinic data on N+ disease that favors combination therapy. In the PSA era, that is 1987 and after, our database data on stage pTxN+ cancer indicates that radical prostatectomy and hormonal therapy for single node positive disease resulted in 94% 10-year cause specific survival, which was not significantly different from the rate in patients with N0 disease after adjusting for local stage, Gleason grade, margins, ploidy, PSA and adjuvant hormonal therapy. CONCLUSIONS: Our literature review, including prospective randomized studies, and more recent results in the PSA era from our database indicate that early adjuvant hormonal therapy has a significant impact on time to progression and cause specific survival in patients with seminal vesicle invasion and limited lymph node disease who undergo radical prostatectomy, although in a retrospective nonrandomized study. Future prospective studies with longer followup are needed to evaluate the potential benefit of adjuvant treatment in regard to survival for stages pT2 and pT3a disease with unfavorable pathological variables.     

Subclassification of the D'Amico's high risk group to predict biochemical recurrence after radical prostatectomy

The D'Amico risk group classification was originally developed to estimate the risk of biochemical recurrence following treatment for localized prostate cancer. We validated the ability of the risk group to predict biochemical recurrence after radical prostatectomy for patients with high-risk prostate cancer. We retrospectively reviewed the medical records of 208 patients who underwent radical prostatectomy, excluding patients with neoadjuvant hormonal therapy, with adjuvant hormonal therapy or radiotherapy, and patients without significant clinical data at our institution between 1997 and 2005. Using the D'Amico risk criteria, 58 (28%), 100 (48%), 50 (24%) were stratified as low-, intermediate- and high-risk groups, respectively. The Kaplan-Meier analysis of biochemical progression-free survival showed that the high-risk group in the D' Amico risk criteria consisted of patients with various prognosis. Therefore, in this group, patients with two or more of three factors including clinical stage T2b or higher, preoperative PSA 10 ng/ml or greater, and biopsy Gleason score 7-10 were reclassified into the very-high-risk group, and those with only one of three factors were reclassified into the semi-high risk group. Patients in the very-high risk group had recurrence at a significantly higher rate than those in the semi-high risk group (p＝0.021). In conclusion, further classification of the D'Amico high risk group into two subgroups has a potential to identify a patient group with very high risk of PSA recurrence after prostatectomy.     

Does Neoadjuvant and Adjuvant Treatment Improve Outcome in Localised Prostatic Cancer?

ObjectivesThis paper reviews neoadjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer.MethodsWe searched MEDLINE (1966–2007). Randomised or quasi-randomised controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1–T4, any N, M0, comparing neoadjuvant or adjuvant hormonal deprivation in combination with primary therapy (radical radiotherapy or radical prostatectomy) versus primary therapy alone were reviewed.ResultsNeoadjuvant hormonal therapy prior to prostatectomy does not improve overall survival. However, a significant reduction was noted in the positive surgical margin rate and a significant improvement in other pathologic variables such as lymph node involvement, pathologic staging, and organ-confined rates. The use of longer duration of neoadjuvant hormones, that is, either 6 or 8 mo prior to prostatectomy, is associated with a significant reduction in positive surgical margins. Neoadjuvant hormones before radiotherapy significantly improves both clinical disease-free survival and biochemical disease-free survival. Adjuvant androgen deprivation following prostatectomy significantly improves disease-free survival at both 5 and 10 yr but does not improve overall survival at 5 yr. Adjuvant therapy following radiotherapy results in a significant improvement in disease-specific survival and disease-free survival at 5 yr and a significant overall survival gain at 5 and 10 yr.ConclusionsHormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. It not only provides a method for local control, but evidence also suggests a significant survival advantage if radiotherapy is the primary form of local therapy.     

Outcome of surgery for clinical unilateral T3a prostate cancer: a single-institution experience

OBJECTIVES: The optimal management of locally advanced prostate cancer (cT3) is still a matter of debate. The objective of this study is to present 10-year outcomes of radical prostatectomy (RP) in unilateral cT3a disease. PATIENTS AND METHODS: Between 1987 and 2004, 2273 patients underwent RP at our institution. Two hundred and thirty-five (10.3%) patients were assessed as unilateral cT3a disease by digital rectal examination. Thirty-five patients who received neoadjuvant treatment before surgery were excluded from further analysis. Mean follow-up was 70.6 months. Kaplan-Meier survival analysis was used to calculate the biochemical progression-free survival (BPFS), clinical progression-free survival (CPFS), cancer-specific survival (CSS), and overall survival (OS) rates. Cox uni- and multivariate regression analyses were used to identify predictive factors in BPFS and CPFS. RESULTS: Clinical overstaging (pT2) occurred in 23.5%. One hundred and twelve (56%) patients received adjuvant or salvage therapy. OS at 5 and 10 years was 95.9% and 77.0%, respectively, and CSS was 98.7% and 91.6%. BPFS at 5 and 10 years was 59.5% and 51.1%, respectively, and CPFS was 95.9% and 85.4%. Margin status was a significant independent predictor in BPFS; cancer volume was a significant independent predictor in CPFS. CONCLUSIONS: Clinically advanced prostate cancer is still frequently overstaged. In a well-selected patient group with locally advanced prostate cancer, RP--with adjuvant or salvage treatment when needed--can yield very high long-term cancer control and survival rates. Margin status and cancer volume are significant predictors of outcome after RP.