Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy for non-metastatic prostate cancer.

The standard treatment options based on the risk category (stage, Gleason score, PSA) for localized prostate cancer include surgery, radiotherapy and watchful waiting. The literature does not provide clear-cut evidence for the superiority of surgery over radiotherapy, whereas both approaches differ in their side effects. The definitive external beam irradiation is frequently employed in stage T1b-T1c, T2 and T3 tumors. There is a pretty strong evidence that intermediate- and high-risk patients benefit from dose escalation. The latter requires reduction of the irradiated normal tissue (using 3-dimensional conformal approach, intensity modulated radiotherapy, image-guided radiotherapy, etc.). Recent data suggest that prostate cancer may benefit from hypofractionation due to relatively low alpha/beta ratio; these findings warrant confirmation though. The role of whole pelvis irradiation is still controversial. Numerous randomized trials demonstrated a clinical benefit in terms of biochemical control, local and distant control, and overall survival from the addition of androgen suppression to external beam radiotherapy in intermediate- and high-risk patients. These studies typically included locally advanced (T3-T4) and poor-prognosis (Gleason score >7 and/or PSA >20 ng/mL) tumors and employed neoadjuvant/concomitant/adjuvant androgen suppression rather than only adjuvant setting. The ongoing trials will hopefully further define the role of endocrine treatment in more favorable risk patients and in the setting of the dose escalated radiotherapy. Brachytherapy (BRT) with permanent implants may be offered to low-risk patients (cT1-T2a, Gleason score <7, or 3+4, PSA 相似文献   

Seminal vesicle involvement in patients with D1 disease predicts early prostate specific antigen recurrence and metastasis after radical prostatectomy and early androgen ablation

BACKGROUND: Controversy persists regarding the management of patients who present with locally advanced metastatic prostate carcinoma. Although radical prostatectomy is not curative, there is growing evidence that survival may be prolonged when the surgery is combined with early androgen ablation. In the current study, the authors present data with which to evaluate and define factors for disease progression in patients undergoing radical prostatectomy with lymph node positive disease who are treated with early endocrine ablation. METHODS: Data from 40 patients undergoing radical prostatectomy and early androgen ablation between 1987-1998, all of whom had lymph node positive disease, were analyzed. Age, preoperative prostate specific antigen (PSA) level, clinical and pathologic Gleason score, surgical margin, seminal vesicle involvement (SVI), and the number and percentage of involved positive lymph nodes were analyzed to predict PSA progression, metastasis, and death using univariate and multivariate statistical techniques. RESULTS: Univariate analysis identified only SVI as a statistically significant predictor of PSA progression and metastasis. Twenty-seven patients (67.5%) were found to have SVI. Multivariate analysis failed to identify other factors that added significantly to the predictive ability of SVI. Kaplan-Meier estimates of time to PSA recurrence and metastasis demonstrated that SVI was highly predictive of disease progression. The median time to PSA progression for the 27 patients with SVI was 7.5 years compared with no progression reported in the 13 patients without SVI (P = 0.011). CONCLUSIONS: VI is a very powerful predictor of disease progression in patients with lymph node positive disease who undergo radical prostatectomy and early androgen ablation. In the current study, preoperative PSA, clinical or pathologic Gleason scores, and other clinical factors were not found to be predictive of disease outcome.     

Prediction by quantitative histology of pathological stage in prostate cancer.

AIMS: To find a predictor of extraprostatic extension in clinically localized prostate cancer (PCa), pre-operative ultrasound-guided prostate needle biopsies and clinico-pathological data were reviewed. METHODS: One hundred and eighty-three consecutive patients who underwent radical retropubic prostatectomy for clinical T1-T2 PCa and serum PSA <10 ng/ml were reviewed. Pre-operative biopsy was performed according to an extended protocol and whole-mount prostatectomy specimens were processed. The following biopsy variables were categorized to this analysis: Gleason score (< or =6, >6), TPC (< or =20%; >20%), GPC (< or =50%; >50%), cancer-positive cores (< or =2; >2), cancer-positive cores in both lateral portions (yes; no), PCa (monolateral; bilateral). RESULTS: Only 60/183 specimens showed an organ-confined PCa; the remaining ones showed pT3a in 57 cases, pT3b in 11 and pT3 with positive surgical margins in 55. A locally advanced PCa was found in 60.2 and 76.8% of T1c and T2 clinical stage, respectively. The positive predictive value and negative predictive value of biopsy findings to predict a locally advanced PCa was 89.9 and 75%, respectively. All biopsy variables associations were statistically significant; however, among these variables (non-categorized), in multivariate logistic regression analysis, only GPC was significantly associated with pathologic stage (odds ratio estimate was 1.075, 95% CI: 1.053-1.098). CONCLUSIONS: Quantitative histology, especially GPC, seems to be helpful for pre-operative staging of PCa in patients with T1c-T2 clinical stage and PSA < 10 ng/ml.     

No residual tumor in a radical prostatectomy specimen after neoadjuvant hormonal therapy for localized prostate cancer

The role of neoadjuvant hormonal therapy (NHT) before radical prostatectomy for localized prostate cancer remains controversial because many argue that apparent downstaging results in difficulties with the pathological evaluation of the neoadjuvant treated prostatectomy specimen. Furthermore, the downstaging to pT0 (no residual tumor), as reported by several institutions, remains questionable and is not yet confirmed by clinical or experimental evidence. To examine this issue and to assess the influence of NHT on downstaging, we investigated the stage pT0 status in radical prostatectomy specimens after NHT. We retrospectively reviewed 31 patients with histologically confirmed clinical stage T1c, T2 or T3 prostate cancer. All patients had received NHT for a mean duration of 5.2 months (range 2-19). We compared the pretreatment parameters (PSA, clinical stage, biopsy Gleason grade, number of positive cores, total length of cancer on each sextant biopsy or duration of NHT) to the pathological findings in the specimen sectioned at 3-mm thick after NHT. Five (16%) of 31 patients had no residual cancer (pT0) after radical prostatectomy, 8 (26%) had organ-confined disease (stage pT2), 6 (19%) had specimen confined disease, 10 (33%) had non-specimen confined disease and only 2 (6%) had lymph node metastasis. The histologic changes, including glandular atrophy and cytoplasmic vacuolation were stronger in specimens with a long duration (4 or more months) of NHT than those of a short duration (3 or less months). Multiple logistic regression analysis showed that only a longer duration of NHT was an independent predictor of a stage pT0 status in radical prostatectomy specimens after NHT (p=0.04, Odds ratio; 1.92, 95% CI; 1.03-3.56). Downstaging to pT0 occurs after duration of NHT of longer than 3 months. Further investigation of the optimal duration of NHT for downstaging and for improving patients' survival should be accomplished in randomized trials.     

Recent advances in the treatment of prostate cancer

As new evidence for prostate cancer treatment has emerged in the last few years, longstanding controversies in the treatment of prostate cancer have resurfaced. A number of long-held tenets of prostate cancer therapy have been revisited, sometimes with surprising and challenging results. Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer. Palliative benefit of chemotherapy for hormone refractory prostate cancer remains an important endpoint; survival advantage has not been seen in any randomized trials. Suramin may delay disease progression in hormone refractory prostate cancer. Many aspects of prostate cancer treatment will remain controversial until results of large, randomized trials with longer follow-up are available.     

Clinical utility of endorectal MRI in determining PSA outcome for patients with biopsy Gleason score 7, PSA <or=10, and clinically localized prostate cancer

PURPOSE: Although the optimal management for patients with high-grade clinically localized prostate cancer is undefined, radical prostatectomy (RP) or external beam radiotherapy (EBRT) is performed. The clinical utility of the pretreatment prostrate-specific antigen (PSA) level (10 ng/mL) and endorectal MRI (erMRI) stage (T3 vs. T2) to stratify PSA outcome after RP in these patients was evaluated. METHODS AND MATERIALS: erMRI was performed in 147 men with biopsy Gleason score >or=7 and 1992 AJCC clinical Stage T1c or T2a disease before RP. Enumerations of the biopsy and prostatectomy Gleason scores, pathologic stage, and margin status were performed for each pretreatment group on the basis of erMRI findings and PSA level. Comparisons were made using a chi-square metric. The median follow-up was 4.5 years (range 1-10 years). Comparisons of the actuarial freedom from PSA failure (bNED) were made using the log-rank test. RESULTS: erMRI Stage T2 and T3 disease was found in 132 and 15 patients, respectively. On stratification by PSA level, patients with erMRI T3 disease had similar bNED outcomes (p = 0.46), regardless of the PSA level. The 3-year bNED rate was 82%, 64%, and 25% (p <0.0001) for Group 1 (erMRI T2 and PSA 10 ng/mL), and Group 3 (erMRI T3 with any PSA level), respectively. The rates of prostatectomy T3 disease, biopsy and prostatectomy Gleason score 8-10, and positive surgical margins were significantly higher (p or=7, PSA 相似文献   

Expression of p21 predicts PSA failure in locally advanced prostate cancer treated by prostatectomy

The management of prostate cancer is based on several clinicopathological criteria. The ability to determine the tumor's biological potential is one goal of tumor markers in order to identify patients who may require more intensive treatment strategies. The purpose of our study was to determine if p21/(WAF1/CIP1) expression can predict biochemical failure in patients with locally advanced prostate cancer treated by radical retropubic prostatectomy (RRP). We used immunohistochemistry to analyze patterns of p21 expression in a population of 296 patients with locally advanced (pT3) prostate cancer treated by RRP. Results were correlated with clinicopathological parameters and time to PSA failure. For the entire cohort of 296 patients, after adjustment for prognostic factors, p21 expression was associated with an increased risk of PSA failure (relative risk [RR] = 1.48) of statistical significance at a median follow-up of 54.5 months. Other parameters that independently predicted the risk of PSA failure included lymph node metastasis and seminal vesicle involvement. Because neoadjuvant hormonal therapy (NHT) is known to lead to involutional changes in prostatic carcinoma, we performed multivariate analyses after stratifying for NHT prior to surgery. Among the 172 patients treated by RRP alone, p21 expression was an independent predictor of PSA failure (RR = 2.30), as were lymph node metastases (RR = 3.19) and pathological grade 5-7 and 8-10 (RR = 2.87 and 3.50, respectively). p21 over-expression is an independent predictor of PSA failure in pT3 patients treated by radical prostatectomy, especially if they did not receive NHT. This tumor marker may help clinicians identify patients who may require adjuvant treatment strategies following radical prostatectomy.     

Treatment strategy for locally advanced prostate cancer

With the increasing aged population, prostate cancer has become one of the commonest malignant tumors in the United States. The incidence of prostate cancer is the highest among malignant tumors in males, and the mortality rate is the second highest following lung cancer. Even when prostate cancer is diagnosed to be in the early stage preoperatively, its excised lesions are often judged pathohistologically to be locally advanced tumor (staging error). Therefore, to estimate the exact pathological stage of excised lesions by preoperative parameters such as clinical T, PSA and biopsy Gleason Score, Partin's nomogram is generally used in the United States. However, according to the annual update version of the 2001 millennium update, radical prostatectomy should not be applied to T3, and it was excluded from the nomogram. Currently, the standard methods for the treatment of locally advanced prostate cancer may be external beam radiotherapy and brachytherapy with neoadjuvant hormonal therapy and intraprostate 125I and 103Pd seeds with neoadjuvant hormonal therapy, although the long-term results are unknown. In our study, similar to a report by Messing et al., adjuvant hormonal therapy might be effective in patients in whom the tumor was diagnosed as being in the early stage but was later found to be N (+) after its operation.     

Is tumor vascularity in prostate core biopsies a predictor of PSA recurrence after radical prostatectomy?

The purposes of this study were to evaluate if tumour vascularity by Chalkley counting (TVC) in prostate core biopsies can be a predictor of PSA recurrence after radical prostatectomy in prostate cancer and to estimate the concordance between the TVC in core biopsies and the subsequently examined prostatectomy specimen. All patients, with Gleason score ≤7 in core biopsy, clinical stage T1 or T2 who had a radical prostatectomy during 1990 - 1997 at Sahlgrenska University Hospital, were selected as a primary group. Patients with neoadjuvant hormonal therapy were excluded. The patients were divided into two groups, one with PSA recurrence and one group without PSA recurrence. 25 patients had PSA recurrence during the follow up period and 25 patients from non-recurrence group were randomly selected. TVC was assessed from the prostate tissue by immunostaining against CD34. TVC was statistically significant predictor of PSA relapse. The PSA-free survival rate was only 17% in patients within the highest TVC quartile compared to 67% in patients within the lowest TVC quartile.     

An update on prostate cancer

Consideration of the number of prostate biopsy samples found to be positive for cancer may add clinically useful information to T stage, Gleason score, and prostate-specific antigen level in predicting outcome after radical prostatectomy. Higher radiation doses and neoadjuvant hormone therapy has been applied successfully to patients with higher risk disease. Brachytherapy has emerged as a modality for localized prostate cancer with outcomes and toxicity being further defined. Efforts to measure and improve quality of life are an important part of prostate cancer research. Standard management of metastatic disease remains androgen ablation, with long-term side effects being recognized. Newer hormonal and chemotherapeutic agents are being explored for patients with metastatic disease.     

The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with locally advanced prostatic carcinoma

PURPOSE: To analyze the results in patients with locally advanced prostatic carcinoma treated by hormonal therapy followed by external radiotherapy using three-dimensional conformal radiation therapy (3D-CRT) boost. METHODS AND MATERIALS: From 1987 to 1995, 46 patients with histologically proven locally advanced adenocarcinoma of the prostate were treated with 3D-CRT at the National Cancer Center Hospital, Tokyo. The neoadjuvant androgen suppression started immediately after the diagnosis followed by radical radiation therapy, according to the prospective protocol. They were treated with photons of 6-14 MV for wide fields and the boost, of which a multiple-leaf collimator of 2-cm width was available. The boosted dose was delivered with the rotational 3D-CRT, after the delivery of whole pelvis 4-field box from a dose of 40-46 Gy up to 66 Gy. The planning target volume encompassed 1 cm outside throughout the clinical target volume, and the prostate and the seminal vesicles were included in the boost field. RESULTS: The 3D-CRT boost treatment completed as planned in all 46 patients. The median follow-up for all the patients was 60 months (range, 5-120 months). Nineteen of 46 patients died. Of these, 11 patients died of the intercurrent diseases. For all 46 patients, the 5- and 8-year overall survival rates were 61.3% and 42.4%, and the 5- and 8-year cause-specific survival rates were 82.4% and 64.4%, respectively. The prostate-specific antigen (PSA) relapse-free rates for 5- and 8-year were 64.6% and 52.5%, and the clinical local control rates for 5 and 8 years were 75.3% and 69.9%, respectively. The preradiation therapy PSA and the Gleason score were the factors that significantly associated with PSA relapse-free survival. Sixteen of 46 patients (35%) showed at least one form of late toxicities. Of these, 3 patients experienced late complications of Grade 3 (urinary, 2, proctitis, 1). CONCLUSION: The treatment results were fairly good and were consistent with those in Western countries, indicating that this study shows the preliminary status of 3D-CRT for the locally advanced prostate cancer in Japan. Preradiation therapy PSA seems to be a significant predictor of PSA relapse-free survival (p = 0.004) after neoadjuvant androgen suppression.     

External beam radiation monotherapy for localized or locally advanced prostate cancer

PURPOSE: We report the treatment results and complications of external beam radiation monotherapy for localized or locally advanced prostate cancer patients. METHODS: Fifty-four patients with T(1b-3a)N(0)(pN(0))M(0) prostate cancer were treated with external beam radiation monotherapy between 1989 and 2001 at four institutes. RESULTS: During the 4-122 month follow-up period (median: 25 months), 11 (20%) patients experienced biochemical failure, including one with simultaneous local recurrence. The 2-year actuarial biochemical control rate was 85%. Univariate analysis showed that the clinical T classification (P = 0.01), Gleason score (P = 0.006), pretreatment PSA (P = 0.02) and PSA nadir value (P = 0.01) were associated with a higher probability of biochemical failure. Multivariate analysis using the Cox proportional hazards model demonstrated that only the PSA nadir value was a strong predictor of PSA recurrence (P < 0.01). Adverse events were mild and tolerable. No severe urinary or bowel complications were observed. CONCLUSIONS: External beam radiation monotherapy is effective for clinically organ-confined prostate cancer with a low incidence of severe complications in a mean follow-up period of 2 years.     

Tumour growth fraction measured by immunohistochemical staining of Ki67 is an independent prognostic factor in preoperative prostate biopsies with small‐volume or low‐grade prostate cancer

Accurate prognostic parameters in prostate biopsies are needed to better counsel individual patients with prostate cancer. We evaluated the prognostic impact of morphologic and immunohistochemical parameters in preoperative prostate cancer biopsies. A consecutive series of prostate biopsies of 279 men (72% with clinical stage T1c and 23% with T2) who subsequently underwent radical prostatectomy was prospectively analysed for Gleason score, number and percentage of positive cores (NPC, PPC), total percentage of biopsy tissue with tumour (TPT), maximum tumour percentage per core (MTP), and expression of Ki67, Bcl‐2 and p53. All biopsy features were significantly associated with at least one feature of the radical prostatectomy specimen. pT stage was independently predicted by PSA, seminal vesicle invasion by Ki67 LI, positive margins by PSA and MTP, large tumour diameter by PSA and PPC, and Gleason score by biopsy Gleason score, MTP, and Ki67 LI, respectively. Biopsy Gleason score, NPC (1 vs. >1), TPT (<7 vs. ≥7%), and Ki67 LI (<10 vs. ≥10%) were significant predictors of biochemical recurrence after radical prostatectomy (p < 0.01, each). KI67 LI was the only independent prognostic factor in case of a low TPT (<7%) or low Gleason score (<7), the hazard ratio being 6.76 and 6.44, respectively. In summary, preoperative Gleason score, NPC, TPT and Ki67 LI significantly predict the risk of recurrence after radical prostatectomy, and Ki67 is an independent prognosticator in biopsies with low‐volume or low‐grade prostate cancer. Analysis of Ki67 LI in these biopsies may help to better identify patients with clinically insignificant prostate cancer. © 2008 Wiley‐Liss, Inc.     

Obesity and mortality in men with locally advanced prostate cancer: analysis of RTOG 85-31

BACKGROUND: Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy and radiation therapy (RT). Whether BMI is associated with prostate cancer-specific mortality (PCSM) was investigated in a large randomized trial of men treated with RT and androgen deprivation therapy (ADT) for locally advanced prostate cancer. METHODS: Between 1987 and 1992, 945 eligible men with locally advanced prostate cancer were enrolled in a phase 3 trial (RTOG 85-31) and randomized to RT and immediate goserelin or RT alone followed by goserelin at recurrence. Height and weight data were available at baseline for 788 (83%) subjects. Cox regression analyses were performed to evaluate the relations between BMI and all-cause mortality, PCSM, and nonprostate cancer mortality. Covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage, and BMI. RESULTS: The 5-year PCSM rate for men with BMI <25 kg/m(2) was 6.5%, compared with 13.1% and 12.2% in men with BMI > or =25 to <30 and BMI > or =30, respectively (Gray's P = .005). In multivariate analyses, greater BMI was significantly associated with higher PCSM (for BMI > or =25 to <30, hazard ratio [HR] 1.52, 95% confidence interval [CI], 1.02-2.27, P = .04; for BMI > or =30, HR 1.64, 95% CI, 1.01-2.66, P = .04). BMI was not associated with nonprostate cancer or all-cause mortality. CONCLUSIONS: Greater baseline BMI is independently associated with higher PCSM in men with locally advanced prostate cancer. Further studies are warranted to evaluate the mechanism(s) for increased cancer-specific mortality and to assess whether weight loss after prostate cancer diagnosis alters disease course.     

Familial prostate cancer: outcome following radiation therapy with or without adjuvant androgen ablation

PURPOSE: To compare the outcome of familial versus sporadic prostate carcinoma after definitive external radiation. METHODS AND MATERIALS: Between 1987 and 1996, 1214 men with clinically localized prostate cancer (T1-T4, N0/NX, M0) received definitive radiation therapy in our department. By retrospective review of charts and questioning of patients, a record on the presence or absence of prostate cancer in a first degree relative was obtained in 1164 men. Univariate and multivariate analysis was performed on these cases with relapse or rising prostate-specific antigen (PSA), local recurrence, metastasis, and survival as endpoints. RESULTS: Familiar prostate cancer was present in 148 of 1164 men (13%). Men with familial disease were slightly but significantly younger (mean 66 years) at diagnosis than those with sporadic disease (mean 68 years) (p = 0.02). Apart from this there were no significant differences between the two groups in T-stage, Gleason score, pretreatment PSA levels, DNA ploidy, or serum testosterone levels. There were no significant differences in treatment parameters including radiation dose and the use of adjuvant androgen ablation. With a median follow-up of 42 months, there was no difference in freedom from relapse or rising PSA at 6 years between those with a family history (54%) and those without a family history (58%) (p = 0.171). Likewise there was no difference between the two groups when local recurrence or metastasis was the endpoint. Multiple subgroup analyses (younger and older; T1/T2 and T3; low Gleason and high Gleason; no androgen ablation and androgen ablation; race) failed to reveal any differences in outcome in any category between familial and sporadic disease. Among patients with a rising post-treatment PSA profile, PSA doubling times were similar in those with sporadic and familial disease. CONCLUSIONS: This study provides no evidence for any substantial difference between familial and sporadic prostate cancer either in clinicopathological features, in response to treatment, or in ultimate outcome.     

Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation

PURPOSE: This retrospective study compares the long-term biochemical disease-free survival for patients undergoing radical prostatectomy, transperineal ultrasound-guided (125)Iodine implantation, or external beam irradiation alone in a tertiary referral community-based hospital. METHODS AND MATERIALS: Five hundred forty patients were available for evaluation, which included: external beam, 132; (125)I, 186; and radical prostatectomy, 222. For the 318 patients referred to the Department of Radiation Oncology, those with T3 disease underwent external beam irradiation while patients with T1 or T2 underwent (125) 0.2 ng/mL or if they had three consecutive increases in their PSA or an increase in their postoperative PSA warranting intervention with androgen ablation or external beam irradiation to the pelvis. RESULTS: Patients were stratified by pretreatment risk groups predicting for post-treatment PSA recurrence. Patients were considered to be at a low or intermediate risk for recurrence if their clinical stage was T1c, T2a, T2b, pretreatment PSA level was 20, or Gleason score was >/= 7. For 132 patients undergoing external beam irradiation, 28 of 37 low or intermediate risk obtained a 1 year nadir PSA of < 1 (76%) while 40% of high risk patients obtained nadir < 1. Of 186 patients undergoing (125)I, 112 of 147 low or intermediate risk (76%) obtained a nadir PSA < 1. Twenty of 39 (51%) high risk obtained a nadir PSA < 1. Of the 222 patients undergoing prostatectomy, 83 of 88 (94%) low or intermediate risk had undetectable levels of PSA at 1 year. One hundred seventeen of 134 (86%) were high risk and had undetectable levels of PSA at 1 year. The biochemical disease-free survival for patients with low or intermediate risk at 5 years is approximately 70% with no significant difference between those patients treated with radical prostatectomy, external beam, or (125)I. For those patients with high risk factors for recurrence, there is no significant difference between ultrasound-guided implant or external beam, but there is a significant improvement in biochemical disease-free survival with radical prostatectomy. CONCLUSION: For patients with low or intermediate risk disease, external beam, ultrasound-guided (125)I, or a radical prostatectomy give comparable long-term biochemical disease-free survival. For patients with high risk disease, a radical prostatectomy provides a significantly improved biochemical disease-free survival. Our current protocols utilize androgen ablation in combination with conformal three-dimensional external beam irradiation or androgen ablation in conjunction with external beam irradiation and (103)Pd seed implantation for patients at high risk for extra capsular disease. It is too early to determine if this combination therapy will give results comparable to radical prostatectomy. For patients who obtain a 1 year nadir PSA of < 1, the biochemical disease-free survival is durable with little risk of subsequent recurrence.     

The efficacy of early adjuvant radiation therapy for pT3N0 prostate cancer: a matched-pair analysis.

PURPOSE: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.     

The clinical utility of the percent of positive prostate biopsies in predicting biochemical outcome following external-beam radiation therapy for patients with clinically localized prostate cancer

PURPOSE: An investigation was performed of the clinical utility of the percent of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome following external-beam radiation therapy (RT) for men with PSA-detected or clinically palpable prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to determine whether the percent of positive prostate biopsies provided clinically relevant information about PSA outcome following external beam RT in 473 men while accounting for the previously established risk groups based on the pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Commission on Cancer (AJCC) clinical T stage. RESULTS: Controlling for the known prognostic factors, the percent of positive prostate biopsies added clinically significant information (p = 0.02) regarding time to PSA failure following RT. Specifically, 76% of the patients in the intermediate risk group (1992 AJCC T(2b) or biopsy Gleason 7 or PSA > 10 ng/mL and < or = 20 ng/mL) could be classified into either an 30% or 85% 5-year PSA control cohort using the preoperative prostate biopsy data. CONCLUSION: The previously validated stratification of PSA outcome following radical prostatectomy (RP) using the percent of positive prostate biopsies in intermediate-risk patients is also clinically significant for men treated with external beam RT. The percent positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and 1992 AJCC clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome following RP or external beam RT.