Correlation of margin status and extraprostatic extension with progression of prostate carcinoma.

BACKGROUND: The correlation of surgical margins and extraprostatic extension (EPE) with progression is uncertain with regard to prostate carcinoma patients treated by radical prostatectomy. The objective of this study was to define factors predictive of cancer progression; emphasis was placed on surgical margins and their relation to extraprostatic extension. METHODS: The study group consisted of 377 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between 1986 and 1993. All specimens were totally embedded and whole-mounted. Patients ranged in age from 41 to 79 years (mean, 65 years). Those with seminal vesicle invasion or lymph node metastasis and those treated preoperatively with radiation or androgen deprivation were excluded. Final pathologic T classifications were pT2a (41 patients), pT2b (237), and pT3a (99). Progression was defined as biochemical failure (prostate specific antigen [PSA] >0.2 ng/mL), clinical or biopsy-proven local recurrence, or distant metastasis. The mean follow-up was 5.8 years (range, 0.2-11.4 years). Seventy-nine patients who received adjuvant treatment within 3 months after surgery were excluded from survival analysis. RESULTS: The overall margin positivity rate was 29%. Seventy-two patients (19%) had only positive surgical margins without evidence of EPE ("surgical incision"), 53 (14%) had only EPE, 37 (10%) had both, and 215 (57%) had neither. Positive margins were correlated with the finding of EPE (P = 0.003). Progression free survival rates at 5 and 10 years were 88% and 67%, respectively. In univariate analysis, preoperative PSA concentration, positive surgical margins, Gleason grade, cancer volume, and DNA ploidy were significant in predicting progression (P values, <0.001, <0.001, 0.01, 0.007, and <0.001, respectively). In multivariate analysis, margin status and DNA ploidy were independent predictors of progression (relative risk for margin status, 1.9; 95% confidence interval [CI], 1.1-3.4; P = 0.03; relative risk for DNA ploidy, 5.1; 95% CI, 2.4-10.9; P<0.001). Among patients with positive margins, 5-year progression free survival was 78% for those with negative EPE and 55% for those with positive EPE. CONCLUSIONS: Surgical margin status and DNA ploidy were independent predictors of progression after radical prostatectomy. To improve cancer control, adjuvant therapy may be considered for patients with positive surgical margins or nondiploid cancer.     

Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes?

PURPOSE: The long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy. METHODS AND MATERIALS: Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS. RESULTS: The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively). CONCLUSIONS: Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.     

Patients at high risk of progression after radical prostatectomy: Do they all benefit from immediate post-operative irradiation? (EORTC trial 22911)

EORTC trial 22911 demonstrated that immediate postoperative irradiation significantly improved biochemical failure free survival (BPFS) compared to wait-and-see (W and S) until relapse in patients with pT2-3 tumours and pathological risk factors after radical prostatectomy. In this study, we have investigated the heterogeneity of the treatment benefit across defined subgroups of patients. Data from 972 patients were used. A risk model was developed in the W and S group and the Log-rank test for heterogeneity was applied (alpha=0.05). Positive surgical margin (SM+), seminal vesicle invasion (SV+), WHO differentiation grade, pre- and post-operative PSA were independent predictors for BPFS in the W and S group. Men with SV+ were at higher risk of relapse whereas those with SM+ but no capsule infiltration (ECE-) did not seem to differ from those with SM-ECE+ or with SM+ECE+. Postoperative irradiation improved biochemical progression-free survival in all patient groups. Longer follow-up is needed to assess the endpoint of clinical progression-free survival.     

Antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles in 614 consecutive patients

BACKGROUND: We present our procedure of antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles and assess the time trends of patient characteristics, surgical and oncological outcome in 614 consecutive patients in a single institution over a 12-year period. METHODS: From April 1994 to December 2005, 614 consecutive Japanese patients with cT1-3N0M0 prostate cancer underwent antegrade radical prostatectomy with preliminary ligation of vascular pedicles (dorsal vein complex and prostatic pedicles) prior to the tumor manipulation. Biochemical progression is defined as prostate-specific antigen value over 0.2 ng/ml or the initiation of therapy after surgery. Biochemical progression-free, cancer-specific and overall survival curves were calculated by the Kaplan-Meier method. RESULTS: During the study period pre-operative PSA, clinical T stage, duration of surgery, amount of estimated blood loss have decreased. Pathological stage showed a significant downward migration and the rate of positive surgical margin has also decreased. At a mean follow-up of 48 months, 21 men were dead including eight who died of prostate cancer. Overall and cancer-specific survival rates were 97/99% at 5 years and 89/95% at 10 years, respectively. Neoadjuvant hormonal treatment had no beneficial impact on oncological outcome of patients regardless of clinical stage. In 370 patients treated surgically alone, cancer-specific and biochemical progression-free survival rates were 99.6/80.5% at 5 years and 97.9/73.3% at 10 years for patients with clinical T1/2 disease and 95.5/41.9% at 5 years and 87.5/41.9% at 10 years for those with T3 disease, respectively. In the 370 patients biochemical progression-free survival has been significantly improved over the 12-year period (P < 0.0001). CONCLUSIONS: Antegrade radical prostatectomy with preliminary ligation of vascular pedicles can be performed with excellent oncological outcome.     

Accuracy of CAPRA-S Score for Predicting Long-Term Biochemical Progression After Radical Prostatectomy

BackgroundThe Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score is a tool to stratify patients into groups according to their risk for biochemical recurrence after radical prostatectomy. The aim of this study was to assess the accuracy of the CAPRA-S score for predicting biochemical progression at 5 and 10 years in our cohort of patients after radical prostatectomy.Patients and MethodsBetween June 2004 and December 2015, radical prostatectomy was performed as the main treatment option for patients with localized prostate cancer. Patients who had received adjuvant or neoadjuvant treatment were excluded from this study. Biochemical progression after radical prostatectomy was considered in patients by prostate-specific antigen (PSA) > 0.1 ng/mL after surgery (biochemical persistence) and by at least 2 determinations of PSA > 0.2 ng/mL in those patients with initial undetectable postoperative PSA any time during their follow-up (biochemical failure). Cox proportional hazard model and Kaplan-Meier analysis were used for the statistical analysis.ResultsOf 531 patients who underwent radical prostatectomy, 479 met the inclusion criteria. Mean follow-up was 85 months (min-max, 13-153 months). The rate of biochemical progression–free survival at 10 years was 84.2%, 55.1%, and 32.8%, respectively, for high-, intermediate-, and low-risk patients according to the CAPRA-S score. The concordance index for CAPRA-S predicting biochemical progression at 5 years was 0.71 and at 10 years was 0.70.ConclusionThe CAPRA-S score is a useful and easy-to-use tool in patients after radical prostatectomy to classify their risk for biochemical progression, thus helping decide if adjuvant treatment should be required.     

Radiation Therapy for Increasing Prostate-Specific Antigen Levels After Radical Prostatectomy

Herein we present data on outcomes in patients with increasing prostate-specific antigen (PSA) levels treated with irradiation to the pelvis and/or prostatic bed after radical prostatectomy. Between 1988 and 1998, 92 patients who presented with increasing PSA levels after radical prostatectomy were treated with irradiation, 29 to the pelvis and prostatic bed and 63 to the prostatic bed only. The mean follow-up was 4 years for the 3D-CRT group and 6.5 years for the standard radiation therapy group. Criterion for biochemical failure was an increase in post irradiation PSA level on ≥ 1 consecutive measurement. Patients were classified into 3 risk groups based on prognostic factors: pathologic tumor extent and stage, Gleason score, and PSA levels before irradiation. Acute and late morbidity was quantitatively evaluated in all patients. There was a close correlation between the preirradiation PSA level and the probability of 4-year biochemical failure–free survival (75% with PSA levels ≥ 1 ng/mL, 30% with PSA levels of 1.1-2 ng/mL, and 20% with PSA levels > 2 ng/mL; P = 0.05). The 4-year chemical failure rate was 20% in the low/intermediate-risk group and 65% in the high-risk group (P = 0.36). In 20 patients in the low-PSA group (≥ 1 ng/mL) receiving doses > 62 Gy, no biochemical failures have been detected in comparison to a 70% failure rate at 4 years in patients treated with lower doses (P = 0.15). In the higher-PSA groups, no impact of irradiation dose on outcome was noted (40%–60% incidence of failure at 3 years). Pelvic irradiation was associated with a trend toward decreased biochemical failure rate in the low-PSA group (70% vs. 0% at 4 years; P = 0.35), but not in the high-PSA group. Only 1 patient (1.5%) experienced clinical local recurrence in the prostatic bed and 2 patients (1.8%) had distant metastases. Treatment has been very well tolerated, with only 3 patients in the arc-rotation group experiencing grade 2 treatment toxicity. Prostate bed irradiation is an effective treatment in a significant proportion of patients who present with a biochemical failure after radical prostatectomy.     

A comparison of external beam radiation therapy versus radical prostatectomy for patients with low risk prostate carcinoma diagnosed, staged, and treated at a single institution

BACKGROUND: The authors retrospectively reviewed their institution's long term experience treating a group of comparably staged low risk prostate carcinoma patients with either radical prostatectomy or external beam radiation therapy (RT) to determine whether the method of treatment resulted in significant differences in biochemical control and/or survival. METHODS: From January of 1987 through December of 1994, 382 patients (157 who underwent radical prostatectomy and 225 who received external beam RT) were treated with curative intent for localized prostate carcinoma at William Beaumont Hospital. All patients had a pretreatment serum prostate specific antigen (PSA) level < or =10.0 ng/mL and a biopsy Gleason score or =0.2 ng/mL at any time after prostatectomy. For RT patients, biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Pretreatment PSA levels and Gleason scores were not significantly different between patients treated with radical prostatectomy or RT. The median follow-up in each treatment group was 5.5 years. RESULTS: The 7-year actuarial rates of biochemical control and cause specific survival were not significantly different between patients treated either with radical prostatectomy or RT (67% vs. 69% for biochemical control and 99% vs. 97% for cause specific survival, respectively). A number of clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical failure (i.e., age, pretreatment PSA, Gleason score, and treatment modality). Only pretreatment PSA and Gleason score were significantly related to outcome in both univariate and multivariate analyses. CONCLUSIONS: Low risk prostate carcinoma patients with similar pretreatment PSA levels and biopsy Gleason scores treated at the same institution with either radical prostatectomy or RT achieved similar 7-year rates of biochemical control and cause specific survival, regardless of treatment technique. These findings suggest that for patients with pretreatment PSA levels 相似文献   

Postoperative radiation therapy after radical prostatectomy for prostate carcinoma.

BACKGROUND. The role and benefit of adjuvant radiation therapy after radical prostatectomy is unclear. This role was evaluated in 58 patients who, after undergoing radical prostatectomy for prostate carcinoma, had local extension of disease beyond the prostate or positive surgical margins. Thirty-nine patients treated surgically alone were compared with 19 patients who received adjuvant postoperative radiation therapy. All patients were followed for at least 5 years, and 50 patients had 10-year follow-ups. RESULTS. At 10 years, the actuarial local failure rate was 31% for patients treated with prostatectomy alone versus 6% for the group receiving postoperative radiation therapy (P less than 0.05). The actuarial survival and metastasis-free survival were similar for both groups. When patients with involved lymph nodes were excluded from analysis, the addition of radiation therapy resulted in improved recurrence-free survival (91% versus 46% at 10 years, P = 0.04) and in a trend toward improved metastasis-free survival (91% versus 55%, P = 0.08). Complications occurred in similar frequencies in both groups. CONCLUSIONS. In patients with local disease extension or positive surgical margins after radical prostatectomy, adjuvant radiation therapy improved local control and was administered with acceptable side effects.     

Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer

Purpose: To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence.Methods and Materials: Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60–70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml.Results: At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure.Conclusion: This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.     

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.     

Biochemical disease-free survival following adjuvant and salvage irradiation after radical prostatectomy

PURPOSE: To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL. RESULTS: The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%. CONCLUSION: This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.     

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.     

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.     

Gleason Pattern 5 is a Possible Pathologic Predictor for Biochemical Recurrence after Laparoscopic Radical Prostatectomy

Objective: Several prognostic factors for biochemical recurrence after radical prostatectomy have been reported,including initial prostate-specific antigen level, Gleason score, positive surgical margin, and seminal vesicle invasion.Here we investigate whether Gleason pattern 5 is a predictor for biochemical recurrence. Methods: This retrospectivestudy included 168 patients who underwent laparoscopic radical prostatectomy from 2006 to 2015. The relationshipbetween biochemical recurrence after laparoscopic radical prostatectomy and the presence of Gleason pattern 5, evenas a tertiary pattern, was investigated. Biochemical recurrence was defined when the prostate-specific antigen levelrose to >0.2 ng/ml after having decreased to recurrence-free survival was estimated by the Kaplan-Meier method. Multivariate analysis was performed using aCox proportional hazards regression model. Results: The median age was 66 years, median initial prostate-specificantigen level was 6.9 ng/ml, and median follow-up period was 47.3 months. Biochemical recurrence was recognizedin 27 patients (16.1%) after laparoscopic radical prostatectomy, and 5-year biochemical recurrence-free survival was78.6%. Gleason pattern 5 was noted in 5 patients as the primary pattern, in 10 as the secondary pattern, and in 5 as thetertiary pattern. According to multivariate analysis, presence of Gleason pattern 5 (HR = 4.75, p=0.001) and positivesurgical margin (HR = 4.66, p=0.001) were independent predictive factors for biochemical recurrence-free survival.Conclusion: Gleason pattern 5 appears to be an important predictive factor for biochemical recurrence after laparoscopicradical prostatectomy.     

Radiation therapy for increasing prostate-specific antigen levels after radical prostatectomy

Herein we present data on outcomes in patients with increasing prostate-specific antigen (PSA) levels treated with irradiation to the pelvis and/or prostatic bed after radical prostatectomy. Between 1988 and 1998, 92 patients who presented with increasing PSA levels after radical prostatectomy were treated with irradiation, 29 to the pelvis and prostatic bed and 63 to the prostatic bed only. The mean follow-up was 4 years for the 3D-CRT group and 6.5 years for the standard radiation therapy group. Criterion for biochemical failure was an increase in post irradiation PSA level on > or = 1 consecutive measurement. Patients were classified into 3 risk groups based on prognostic factors: pathologic tumor extent and stage, Gleason score, and PSA levels before irradiation. Acute and late morbidity was quantitatively evaluated in all patients. There was a close correlation between the preirradiation PSA level and the probability of 4-year biochemical failure-free survival (75% with PSA levels < or = 1 ng/mL, 30% with PSA levels of 1.1-2 ng/mL, and 20% with PSA levels > 2 ng/mL; P = 0.05). The 4-year chemical failure rate was 20% in the low/intermediate-risk group and 65% in the high-risk group (P = 0.36). In 20 patients in the low-PSA group (< or =1 ng/mL) receiving doses > 62 Gy, no biochemical failures have been detected in comparison to a 70% failure rate at 4 years in patients treated with lower doses (P = 0.15). In the higher-PSA groups, no impact of irradiation dose on outcome was noted (40%-60% incidence of failure at 3 years). Pelvic irradiation was associated with a trend toward decreased biochemical failure rate in the low-PSA group (70% vs. 0% at 4 years; P = 0.35), but not in the high-PSA group. Only 1 patient (1.5%) experienced clinical local recurrence in the prostatic bed and 2 patients (1.8%) had distant metastases. Treatment has been very well tolerated, with only 3 patients in the arc-rotation group experiencing grade 2 treatment toxicity. Prostate bed irradiation is an effective treatment in a significant proportion of patients who present with a biochemical failure after radical prostatectomy.     

Benefit on biochemical control of adjuvant radiation therapy in patients with pathologically involved seminal vesicles after radical prostatectomy

AIMS AND BACKGROUND: To determine whether there is a benefit for biochemical control with adjuvant radiation therapy to the surgical bed following radical prostatectomy in patients with seminal vesicle invasion and pathologically negative pelvic lymph nodes (pT3b-pT4 pN0). METHODS: We retrospectively reviewed the clinical records of radical prostatectomy patients treated between 1995 and 2002. A total of 66 patients with seminal vesicle invasion were identified: 45 of these patients received adjuvant radiation therapy and 21 were observed. Radiation therapy was initiated within 4 months of prostatectomy. Median dose was 66 Gy (range, 60-70 Gy). Median follow-up from the day of surgery was 40.6 months (mean, 41.5; range, 12-99). Biochemical recurrence was defined as the first value > or = 0.2 ng/ml. RESULTS: At two years, the proportion of patients free from biochemical recurrence was 80% in patients who received adjuvant radiation therapy versus 54% for those not given radiation therapy (P = 0.036). Actuarial biochemical recurrence at 5 years was 59% vs 41% for the radiation therapy and no radiation therapy groups, respectively. On univariate Cox regression model, the hazard of biochemical failure was also associated with a detectable (> or = 0.2 ng/ml) postsurgical prostate-specific antigen (P = 0.02) prior to radiation therapy. Pathological T stage (pT3b vs pT4), Gleason score, primary Gleason pattern and positive surgical margins were not significantly associated with biochemical recurrence. The hazard of biochemical failure was around 85% lower in the radiation therapy group than in the observation group (P = 0.002). CONCLUSIONS: Data from the present series suggest that adjuvant radiation therapy for patients with seminal vesicle invasion and undetectable (< or = 0.2 ng/ml) postoperative prostate-specific antigen significantly reduces the likelihood of biochemical failure.     

Prognostic significance of positive surgical margins in patients with extraprostatic carcinoma after radical prostatectomy

BACKGROUND: A significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma. METHODS: The Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987-1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis. RESULTS: A total of 354 patients (42%) had > or = 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had > or = 2 positive surgical margins. The 5-year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with > or = 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18-2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy. CONCLUSIONS: In the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence-free survival remains to be tested.     

Postoperative radiotherapy for carcinoma of the prostate: impact on both local control and distant disease-free survival

The role of postoperative irradiation in patients with clinically localized prostate cancer, either as an adjuvant or salvage radiotherapy, remains controversial. In this study, we evaluate the impact of postoperative radiotherapy on patients diagnosed with prostate cancer with respect to biochemical and clinical disease free survival. Between 1987 and 1996, 179 patients with clinically localized prostate cancer were found to have adverse histopathologic findings on radical prostatectomy specimens (positive surgical margins, extracapsular extension, and seminal vesicle invasion). Of these patients, 42 were referred for postoperative adjuvant radiotherapy, whereas 73 were referred for salvage irradiation because of rising serum prostate-specific antigen (PSA) levels postoperatively. The remaining 64 patients underwent prostatectomy only. The 10-year biochemical relapse-free survival (RFS) from date of surgery were 88%, 45%, and 25% for patients treated with postoperative adjuvant radiotherapy, salvage irradiation, and with surgery alone, respectively (p = 0.046). Ten-year distant RFS from date of surgery were 82%, 74%, and 44% for adjuvantly treated patients, those with salvage radiotherapy, and those with surgery alone, respectively (p = 0.0180). Ten-year overall disease RFS from date of surgery was 89%, 76%, and 30% for adjuvantly treated patients, those with salvage radiotherapy, and those with surgery alone, respectively (p = 0.0237). Multivariate analyses revealed that a preoperative PSA greater than 20 ng/ml and pathologic Gleason Score of 8 to 10 were adverse predictors for biochemical relapse, whereas pathologic Gleason Score of 8 to 10, seminal vesicle invasion, and extracapsular extension were adverse predictors of distant metastases. Postoperative radiotherapy, either delivered as adjuvant treatment for adverse histopathologic findings or as salvage therapy for local relapses, appear to confer superior local, distant disease RFS, and overall disease RFS than surgery alone.     

Definitive radiotherapy following prostatectomy: results and complications

Thirty-four patients with carcinoma of the prostate treated by prostatectomy received postoperative external beam radiation. Sixteen patients were treated within 4 months of radical prostatectomy (group 1), 12 patients were treated for prostate carcinoma following initial enucleative prostatectomy for benign hypertrophy (group 2) and 6 patients were treated for palpable local recurrence 4 to 10 years following radical prostatectomy (group 3). The indications for postoperative radiotherapy following radical prostatectomy included extracapsular extension, seminal vesicle invasion, peri-prostatic soft tissue involvement, positive margins or palpable local recurrence. Eighty-five percent of the patients received whole pelvic radiation. All patients then had a 2-week treatment rest followed by a reduced portal to the prostate bed to a dose of 6500 cGy. The local control rate after radiotherapy was 100% with a median follow-up of 4 years. The 5-year actuarial survival and disease-free survival rates for all patients were 82 and 72%, respectively. In group 1, the 5-year actuarial survival and disease-free survival rates were 100 and 91%, respectively. In group 2, these rates were 77 and 64%. Three of the six patients in group 3 died within 30 months of radiotherapy. Fourteen patients (41%) had mild to moderate treatment related symptoms including seven patients (21%) with lower extremity or genital edema, five patients (15%) with urinary stress incontinence, two patients (6%) with urethral stricture and three patients (9%) with proctitis. Six of eight patients who were potent prior to radiation retained potency thereafter. No severe complications occurred. We conclude that external beam radiation therapy administered after prostatectomy resulted in an acceptable therapeutic ratio with 100% local regional control, and an acceptable complication rate (41%).     

Risk of prostate carcinoma death in patients with lymph node metastasis

BACKGROUND: The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS: The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) > or = 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS: The 5-year and 10-year progression free survival rates (+/- standard error [SE]) for patients with lymph node metastasis were 74% +/- 2% and 64% +/- 3%, respectively, compared with 77% +/- 1% and 59% +/- 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% +/- 1% and 83% +/- 4%, respectively, compared with 99% +/- 0.1% and 97% +/- 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% +/- 1% and 94% +/- 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5-5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9-19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4-13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7-1.3; P = 0.90). CONCLUSIONS: Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes.