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Keywords:

  • Gleason score 8 to 10;
  • high risk;
  • prostate cancer;
  • recurrence;
  • radical prostatectomy

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

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 ≥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. Cancer 2006. © 2006 American Cancer Society.

The majority of patients today present with nonpalpable, clinical stage T1c, Gleason sum 6 tumors, and prostate-specific antigen (PSA) values <10 ng/mL and thus have a high likelihood of disease-free survival, regardless of the treatment option chosen.1 In contrast, patients with high-risk prostate cancer (i.e., biopsy Gleason sum ≥8, a PSA value ≥20 ng/mL, and clinical stage disease ≥T2c) are at high risk of treatment failure.2 In recent series of patients treated by surgical monotherapy, approximately 4% to 12% of patients had a biopsy Gleason sum ≥8.3–7 Given the migration to a lower stage of disease at presentation, these patients may theoretically be appropriate candidates for local therapy alone if diagnosed early in the disease process.8 The goal of pretreatment evaluation in patients with Gleason sums 8 to 10 should be to identify those who would benefit most from local therapy and those who should be considered for early systemic therapy. To accomplish this, we retrospectively reviewed outcomes among men with a Gleason sum of ≥8 treated by surgical monotherapy to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome. To increase the generalizability of our findings, we used data 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).

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Johns Hopkins Study Population

After obtaining Institutional Review Board approval and informed consent when appropriate, consecutive patients treated with retropubic radical prostatectomy for prostate adenocarcinoma from 1982 to 2004 at the Johns Hopkins Hospital who had follow-up information available were identified. Among 6446 men with follow-up information available, 45 had an unknown biopsy Gleason sum. Among the remaining 6401 men, 242 (3.8%) had a biopsy Gleason sum of 8, 9, or 10. Of these 242 men, those treated with preoperative hormonal (luteinizing hormone-releasing hormone agonist, antiandrogen, or 5-α reductase type II inhibitor) therapy (n = 6) or radiation therapy (n = 1) were excluded. Men with missing data for preoperative PSA (n = 15) were excluded, resulting in a study population of 220 men. No patient received adjuvant radiation or hormonal therapy before biochemical progression, defined as a single PSA ≥0.2 ng/mL. The prostatectomy specimens were sectioned as previously described.9

SEARCH Database Study Population

After obtaining Institutional Review Board approval from each institution, patients undergoing radical prostatectomy since 1988 at the Veterans Affairs (VA) Health Care Facilities in West Los Angeles, Palo Alto, San Francisco, and Augusta, Georgia, as well as the San Diego Naval Hospital were combined into 1 database, the SEARCH database.10

Patients treated with preoperative androgen deprivation or radiation therapy were excluded. Of the 2139 men enrolled in the SEARCH Database, 99 men had missing data for biopsy Gleason sum. Of the remaining 2040 men, 157 (7.7%) had a biopsy Gleason sum of 8, 9, or 10. Men with missing data for preoperative PSA (n = 8) were excluded, resulting in a study population of 149 men.

The prostatectomy specimens were sectioned per each institution's protocol.10 No patient received adjuvant radiation or hormonal therapy before biochemical progression, defined as a single PSA >0.2 ng/mL or 2 values at 0.2 ng/mL or secondary treatment for an elevated PSA.

Statistical Analysis

We examined the significant preoperative predictors of unfavorable pathologic findings (nonorgan-confined disease and/or positive surgical margins) using logistic regression. For multivariable analysis, a forwards-stepwise logistic regression analysis was used with a P-value <.15 as the criterion for entry into the model. The variable with the highest P-value was then successively deleted until only variables with a P-value of <.1 remained. The variables considered for entry in the model included age (continuous), preoperative PSA (continuous after logarithmic transformation), race (white vs. nonwhite), year of surgery (continuous), clinical stage (T1 vs. T2/T3), and percent of cores with cancer (number of cores with cancer divided by total number of cores obtained; SEARCH Database only).

Time to biochemical progression was assessed using Kaplan-Meier plots. To identify the significant predictors of time to biochemical progression we used a Cox proportional hazards regression model. For multivariable analysis, a forwards-stepwise logistic regression analysis was used with a P-value <.15 as the criterion for entry into the model. The variable with the highest P-value was successively deleted until only variables with a P-value of <.1 remained. The variables considered for entry in the model included age, preoperative PSA, race, year of surgery, and clinical stage. All statistical analyses were performed using STATA 9.1 software (StataCorp, College Station, TX).

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The clinical and pathologic data from men with biopsy Gleason sums of 8, 9, and 10 from the Johns Hopkins and SEARCH cohorts are shown in Table 1. The majority of patients from both cohorts were white, had clinically palpable disease (clinical stage T2 or higher), and had a biopsy Gleason sum of 8.

Table 1. Clinical and Pathologic Features of Men Undergoing Radical Prostatectomy with a Biopsy Gleason Sum of ≥8
 Johns HopkinsSEARCH Database
  1. SEARCH indicates Shared Equal Access Regional Cancer Hospital database; SD, standard deviation; PSA, prostate-specific antigen.

No. of patients220149
Race
 White189 (89)97 (66)
 Black14 (7)30 (21)
 Other9 (4)19 (13)
Mean age ± SD, y60.3 ± 6.563.3 ± 6.3
PSA, ng/mL
 Mean ± SD11.2 ± 9.414.6 ± 19.1
 Median8.79.4
Clinical T classification (%)
 T1b3 (1)0 (0)
 T1c76 (35)52 (36)
 T2a62 (28)43 (29)
 T2b44 (20)36 (25)
 T2c/T335 (16)15 (10)
No. biopsy Gleason sum (%)
 8158 (72)120 (81)
 959 (27)25 (17)
 103 (1)4 (3)
No. pathologic Gleason sum (%)
 4–615 (7)20 (14)
 7 (3+4)27 (12)33 (23)
 7 (4+3)32 (15)26 (18)
 874 (34)30 (21)
 969 (32)34 (23)
 102 (1)2 (1)
No. organ-confined, negative margins (%)47 (21)58 (41)
No. positive margins (%)64 (29)67 (47)
No. extraprostatic extension (%)166 (75)69 (49)
No. seminal vesicle invasion (%)56 (25)32 (22)
No. lymph node metastasis (%)37 (17)9 (6)

Overall, a favorable pathologic outcome defined as organ-confined disease with negative surgical margins was observed among 21% of the men in the Johns Hopkins cohort and 41% of men in the SEARCH cohort. On multivariable analysis, serum PSA was the only variable that significantly predicted an unfavorable pathologic outcome among men in both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002, Table 2). In the Johns Hopkins cohort, higher clinical stage (P = .038) and earlier year of surgery (P = .038) also predicted an unfavorable pathologic outcome. When only men with 6 or more biopsy cores obtained within the SEARCH database were analyzed (n = 119 or 80% of cohort), the percent of cores with cancer (hazard ratio [HR] 6.26, 95% confidence interval [CI], 1.35–29.08; P = .02) but not preoperative PSA was a significant independent predictor of unfavorable pathologic outcome.

Table 2. Multivariable Logistic Regression Analysis of Factors Predicting a Nonfavorable Pathologic Disease at the Time of Radical Prostatectomy (Nonorgan-Confined or Positive Surgical Margins)
 Odds Ratio95% CIP
  1. 95% CI indicates 95% confidence interval; PSA, prostate-specific antigen; SEARCH, Shared Equal Access Regional Cancer Hospital database.

Johns Hopkins
 Clinical stage (T2/3 relative to T1)2.971.45–6.06.003
 Year of surgery0.910.83–0.99.038
 Serum PSA1.731.01–2.98.047
SEARCH
 Serum PSA2.411.38–4.22.002

The 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% CI, 33–48%) and 27% (95% CI, 18–36%), respectively. The estimated 5-year and 10-year biochemical-free survival rates in the SEARCH cohort were 32% (95% CI, 22–42%) and 28% (95% CI, 18–38%), respectively (Fig. 1). Among men with favorable pathologic findings (organ-confined and negative surgical margins), the 5-year 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%), respectively, in the SEARCH cohort (Fig. 2). Among men with a pathologic Gleason sum <8, the 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 62% (95% CI, 48–73%) and 38% (95% CI, 15–62%), respectively, and 34% (95% CI, 20–49%) and 34% (95% CI, 20–49%), respectively, in the SEARCH cohort (Fig. 3).

thumbnail image

Figure 1. The 10-year actuarial Kaplan-Meier estimates of biochemical progression-free survival of patients with a biopsy Gleason sum ≥8 who were treated with radical prostatectomy at Johns Hopkins Hospital and within the Shared Equal Access Regional Cancer Hospital (SEARCH)Database. PSA indicates prostate-specific antigen.

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thumbnail image

Figure 2. The 10-year actuarial Kaplan-Meier estimates of biochemical progression-free survival of patients with a biopsy Gleason sum ≥8 and organ-confined disease and negative surgical margins who were treated with radical prostatectomy at Johns Hopkins Hospital and within the Shared Equal Access Regional Cancer Hospital (SEARCH)Database. PSA indicates prostate-specific antigen.

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thumbnail image

Figure 3. The 10-year actuarial Kaplan-Meier estimates of biochemical progression-free survival of patients with a biopsy Gleason sum ≥8 but pathological Gleason <8 who were treated with radical prostatectomy at Johns Hopkins Hospital and within the Shared Equal Access Regional Cancer Hospital (SEARCH)Database. PSA indicates prostate-specific antigen.

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On multivariable analysis, higher PSA values (P = .007) and more advanced clinical stage (P = .029) were associated with greater risk of biochemical recurrence in the SEARCH Database, whereas more recent year of surgery was associated with better outcomes in the Johns Hopkins cohort (P < .001) (Table 3). In contrast to the Johns Hopkins cohort, more recent year of surgery was associated with worse outcomes in the SEARCH cohort (P = .057), although the association did not reach statistical significance. The percent of biopsy cores with cancer was not independently associated with progression risk in the whole SEARCH cohort or when analyses were restricted to men with 6 or more biopsy cores obtained.

Table 3. Multivariable Cox Proportional Hazards Analysis of Factors Predicting Time to Biochemical Recurrence after Radical Prostatectomy
 Hazards Ratio95% CIP
  1. 95% CI indicates 95% confidence interval; SEARCH, Shared Equal Access Regional Cancer Hospital database; PSA, prostate-specific antigen.

Johns Hopkins
 Year of surgery0.930.89–0.97<.001
SEARCH
 Serum PSA1.501.12–2.02.007
 Clinical stage (T2/3 vs. T1)1.831.06–3.15.029
 Year of surgery1.071.00–1.14.057

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

In contemporary surgical series, the incidence of a biopsy Gleason sum of ≥8 is approximately 4% to 12%.3–7 Traditionally, these patients were not considered good candidates for radical prostatectomy because of a poor long-term cancer-specific survival and the high incidence of positive pelvic lymph nodes.11, 12 However, the Mayo group has argued that radical prostatectomy is the most appropriate form of therapy for patients with high-risk prostate cancer.8, 13 Likewise, a series by Partin et al.14 suggested that patients with high-grade prostate cancer and negative pelvic nodes may benefit from radical prostatectomy.

Given that studies have found that men with biopsy Gleason sum 8 to 10 cancers are at increased risk of adverse pathologic findings,14 biochemical progression after definitive therapy,2 and prostate cancer death,15 the optimal treatment for these patients remains controversial. Despite this increased risk for adverse outcomes, it is not uncommon that these men are treated with surgical monotherapy and they account for 4% to 12% of all patients undergoing radical prostatectomy in contemporary series.3–7 Several studies have examined outcomes among men with a Gleason sum of ≥8 tumor in the radical prostatectomy specimen and found that overall outcomes are poor.3, 8, 16–19 However, it is not always possible to identify men with high-grade disease in the radical prostatectomy specimen before surgery.3, 8 Therefore, we sought to address outcomes specifically among men with a biopsy Gleason sum of 8 to 10. To increase the generalizability of our findings, we used data from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (SEARCH Database).

We found that the majority of patients presented with extraprostatic disease and/or positive surgical margins with only 21% and 41% of the patients having organ-confined margin-negative disease in the Johns Hopkins and SEARCH cohorts, respectively. The lower rate of organ-confined margin-negative disease in the Johns Hopkins series may relate to the fact that the specimens were serially sectioned and totally submitted, in the Johns Hopkins cohort compared to partial sampling in the SEARCH series, such that the majority of men with unfavorable pathology were correctly identified. However, it should be noted that the incidence of organ-confined disease of 21% to 41% in the current study closely mirrors the 30% noted in a previous report of men with biopsy Gleason sum 8 to 10 tumors.4

The overall 5-year and 10-year PSA-free survival was 40% and 27% in the Johns Hopkins patients, respectively, and was nearly identical to the SEARCH cohort (32% and 28%, respectively). Moreover, these numbers are very similar to the 38% 5-year PSA-free survival risk among men with a biopsy Gleason sum 8 to 10 tumors and a PSA level <20 ng/mL who are treated with radical prostatectomy in the community-based CaPSURE Database.20 The similarity of outcomes among men with high-grade disease across multiple different practice settings (i.e., tertiary care referral center, equal-access medical centers, and community hospitals) strongly suggests that for men with high-risk disease, the biologic potential of the disease will determine clinical outcome and the center at which the surgery was performed becomes less important. It is worth noting that the PSA-free survival rates reported in the current study are less than reported by Manoharan et al.,4 who found a 62% PSA-free survival rate with a median follow-up of 4 years. However, in the prior series many of the highest-risk patients, based on pathologic findings, received adjuvant therapy and were therefore censored from analysis. Therefore, it is difficult to directly compare results from that study with the current study, where no patients received adjuvant therapy before PSA recurrence.

In an earlier report from Johns Hopkins in 1994, we found that for men with biopsy Gleason sum 8 to 10 tumors, the 5-year PSA-free survival rate was 43%—a rate very similar to the current more contemporary series.14 Moreover, we have recently found that among men in the SEARCH Database with high-risk disease based on either PSA or biopsy Gleason sum, outcomes have not improved over time.21 Indeed, in the current study, although more recent year of surgery was associated with better outcomes in the Johns Hopkins series, it was associated with worse outcomes in the SEARCH series. Taken together, these findings suggest that despite a general stage migration for prostate cancer, outcomes among men with high-grade disease have not dramatically improved in the last 10 years.

It was disappointing that even among men with organ-confined disease and negative surgical margins or those with a pathologic Gleason sum <8, the risk of PSA progression was high. In both the SEARCH and Johns Hopkins series, approximately half of the men with favorable pathologic findings or pathologic Gleason sum <8 experienced a PSA progression by 10 years after surgery. Indeed, among men with favorable pathologic findings or pathologic Gleason sum <8, approximately 25% developed disease progression within 2 years after surgery, suggesting that some of these men may have had micrometastatic disease at the time of surgery and may be best served with early systemic therapy. However, it is also noteworthy that nearly half of the PSA recurrences occurred after 2 years after surgery. The clinical relevance is that delayed recurrences are more likely to be local-only recurrences and potentially still curable with local salvage therapies such as radiation.22 This suggests that the combination of surgery plus adjuvant/salvage radiation therapy may be able to improve outcomes among some of these high-risk men.

Although outcomes among men with favorable pathologic findings or pathologic Gleason sum <8 appeared to be slightly better in the Johns Hopkins series (Figs. 2 and 3), by 10 years after surgery outcomes were nearly identical. It is possible that serially sectioned and totally submitted specimens at Johns Hopkins as opposed to partial sampling correctly identified all men with adverse pathology. As such, some of the men in the SEARCH database who were reported to have favorable pathology may indeed have had unfavorable pathologic findings, potentially biasing the SEARCH series to have worse biochemical outcomes in addition to explaining the higher rate of favorable pathologic findings within the SEARCH cohort. In terms of the slightly better short-term outcomes among men in the Johns Hopkins series with Gleason <8 tumors, this may relate to controversy regarding Gleason grading for men with <5% Gleason Pattern 3. At Johns Hopkins, these tumors are graded as 4+4 with a tertiary Grade 3. However, given the multiple pathologists across multiple institutions that encompass the SEARCH database, it is possible that at least some of these tumors were graded as 4+3. This would help to explain the greater prevalence of Gleason sum <8 tumors within the SEARCH Database as well as resulting in the inclusion of higher-risk men in the lower Gleason grade group in the SEARCH Database, thus biasing the SEARCH series to have worse biochemical outcomes.

Higher serum PSA values were correlated with greater risk of advanced disease in both cohorts and greater risk of biochemical progression in the SEARCH cohort. This mirrors data from other studies that PSA is an important prognostic variable for men undergoing radical prostatectomy in general,23, 24 and re mains important when only men with biopsy Gleason sum 8 to 10 tumors are examined.20 In addition to PSA, the only other consistent prognostic factor in the current study was higher clinical stage, which was correlated with adverse pathology in the Johns Hopkins series and disease progression in the SEARCH series. This finding suggests that digital rectal examination remains a valuable tool during the diagnosis and treatment planning of men with prostate cancer.

The percent of biopsy cores with cancer, which is a known prognostic factor for biochemical outcome25 and the risk of prostate cancer death after definitive therapy,26 was not found to be significantly related to progression among men in the SEARCH Database. Thus, even a small volume disease of biopsy could not mitigate the high-risk of progression among men in the current series.

It is not uncommon for the biopsy Gleason sum to be different from the pathologic Gleason sum.8, 27 Thus, based on pathologic Gleason sum, some patients in the current study would not have been categorized as high-risk. In fact, 34% of the Johns Hopkins patients and 55% of the SEARCH patients had a Gleason sum of <8 in the radical prostatectomy specimen. This degree of overgrading for men with a biopsy Gleason sum 8–10 cancer has been noted previously.4 However, even among men who were downgraded (i.e., pathologic Gleason sum <8), outcomes were poor, with the majority of patients experiencing biochemical disease progression. Thus, despite either favorable pathologic findings or lower-grade disease in the radical prostatectomy specimen, men with high-grade disease on biopsy should be viewed as high-risk patients.

We examined biochemical progression as our endpoint. Several studies found that among men treated with radical prostatectomy a shorter time to biochemical progression is associated with increased risk for prostate cancer death.28 Although recent studies suggested that postoperative PSA doubling time may be a better surrogate than biochemical progression for prostate cancer-specific mortality, PSA doubling times were not available on all our patients.29 Other important preoperative prognostic information such as preoperative PSA velocity and percent of biopsy tissue with cancer were also not available on all patients. It is possible that these characteristics may help further risk-stratify men with high-grade disease. It should be noted that recurrences were recorded annually in the Johns Hopkins series (i.e., Year 1 vs. Year 2 vs. Year 3, etc.), whereas in the SEARCH Database recurrences were recorded at the date of actual PSA recurrence. This slight difference in recurrence definition prevents meaningful statistical comparisons between the cohorts. However, the biochemical progression-free survival estimates (Fig. 1) were nearly identical at each year mark, suggesting that overall outcomes were comparable between the cohorts. Finally, it is likely that subtle differences in findings regarding the importance of serum PSA, clinical stage, and year of surgery between the Johns Hopkins and SEARCH series may relate to the overall small numbers of patients. These findings need to be confirmed in future larger studies.

Taking advantage of the rapid advances in understanding the molecular carcinogenesis of prostate cancer, new molecular tests may provide information that is useful for screening, detection, staging, and prognosis.30 Novel imaging techniques may also distinguish between suitable candidates for mono- or multimodal therapy.31, 32 It remains to be determined whether earlier use of radiotherapy, hormonal therapy, chemotherapy, or immunotherapy can improve outcomes among these high-risk men. However, given that these patients are high-risk regardless of pathologic findings, these patients should be encouraged to enroll in clinical trials to address this issue.

Conclusions

Among men with a biopsy Gleason sum of 8 to 10 treated by surgical monotherapy at a tertiary care referral center or at multiple equal-access medical centers, overall outcomes were poor, with only approximately 30% of patients being PSA-free 10 years after surgery. Even among men with organ-confined, surgical margin-negative disease or pathologic Gleason sum <8 tumors, 10-year recurrence rates were ≥50%. Men with high-grade disease on biopsy are good candidates for multimodal therapy. Although 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.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
  • 1
    Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am. 2001; 28: 555565.
  • 2
    D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998; 280: 969974.
  • 3
    Tefilli MV, Gheiler EL, Tiguert R, et al. Role of radical prostatectomy in patients with prostate cancer of high Gleason score. Prostate. 1999; 39: 6066.
  • 4
    Manoharan M, Bird VG, Kim SS, Civantos F, Soloway MS. Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of ≥8. BJU Int. 2003; 92: 539544.
  • 5
    Bianco FJJr., Scardino PT, Eastham JA. Radical prostatectomy: long-term cancer control and recovery of sexual and urinary function (“trifecta”). Urology. 2005; 66(5 Suppl ): 8394.
  • 6
    Saranchuk JW, Kattan MW, Elkin E, Touijer AK, Scardino PT, Eastham JA. Achieving optimal outcomes after radical prostatectomy. J Clin Oncol. 2005; 23: 41464151.
  • 7
    Khan MA, Mangold LA, Epstein JI, Boitnott JK, Walsh PC, Partin AW. Impact of surgical delay on long-term cancer control for clinically localized prostate cancer. J Urol. 2004; 172(5 Pt 1): 18351839.
  • 8
    Lau WK, Bergstralh EJ, Blute ML, Slezak JM, Zincke H. Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables. J Urol. 2002; 167: 117122.
  • 9
    Epstein JI, Pizov G, Walsh PC. Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer. 1993; 71: 35823593.
  • 10
    Freedland SJ, Amling CL, Dorey F, et al. Race as an outcome predictor after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Urology. 2002; 60: 670674.
  • 11
    Khan MA, Partin AW. Management of high-risk populations with locally advanced prostate cancer. Oncologist. 2003; 8: 259269.
  • 12
    Gerber GS, Thisted RA, Chodak GW, et al. Results of radical prostatectomy in men with locally advanced prostate cancer: multi-institutional pooled analysis. Eur Urol. 1997; 32: 385390.
  • 13
    Zincke H, Fleming TR, Furlow WL, Myers RP, Utz DC. Radical retropubic prostatectomy and pelvic lymphadenectomy for high-stage cancer of the prostate. Cancer. 1981; 47: 19011910.
  • 14
    Partin AW, Lee BR, Carmichael M, Walsh PC, Epstein JI. Radical prostatectomy for high grade disease: a reevaluation 1994. J Urol. 1994; 151: 15831586.
  • 15
    Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. 2005; 293: 20952101.
  • 16
    Mian BM, Troncoso P, Okihara K, et al. Outcome of patients with Gleason score 8 or higher prostate cancer following radical prostatectomy alone. J Urol. 2002; 167: 16751680.
  • 17
    Oefelein MG, Smith ND, Grayhack JT, Schaeffer AJ, McVary KT. Long-term results of radical retropubic prostatectomy in men with high grade carcinoma of the prostate. J Urol. 1997; 158: 14601465.
  • 18
    Sciarra A, Gentile V, Voria G, et al. Role of radical retropubic prostatectomy in patients with locally advanced prostate cancer: the influence of Gleason score 8–10. Urol Int. 2003; 70: 186194.
  • 19
    Rioux-Leclercq NC, Chan DY, Epstein JI. Prediction of outcome after radical prostatectomy in men with organ-confined Gleason score 8 to 10 adenocarcinoma. Urology. 2002; 60: 666669.
  • 20
    Grossfeld GD, Latini DM, Lubeck DP, Mehta SS, Carroll PR. Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer. J Urol. 2003; 169: 157163.
  • 21
    Kane CJ, Presti JCJr., Amling CL, Aronson WJ, Terris MK, Freedland SJ. Changing nature of high-risk patients undergoing radical prostatectomy. J Urol. In press.
  • 22
    Trapasso JG, deKernion JB, Smith RB, Dorey F. The incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy. J Urol. 1994; 152(5 Pt 2): 18211825.
  • 23
    Freedland SJ, Mangold LA, Walsh PC, Partin AW. The prostatic specific antigen era is alive and well: prostatic specific antigen and biochemical progression following radical prostatectomy. J Urol. 2005; 174(4 Pt 1): 12761281; Discussion 1281; Author Reply 1281.
  • 24
    Antenor JA, Roehl KA, Eggener SE, Kundu SD, Han M, Catalona WJ. Preoperative PSA and progression-free survival after radical prostatectomy for Stage T1c disease. Urology. 2005; 66: 156160.
  • 25
    Freedland SJ, Aronson WJ, Terris MK, et al. Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database. J Urol. 2003; 169: 21362141.
  • 26
    D'Amico AV, Renshaw AA, Cote K, et al. Impact of the percentage of positive prostate cores on prostate cancer-specific mortality for patients with low or favorable intermediate-risk disease. J Clin Oncol. 2004; 22: 37263732.
  • 27
    Grossfeld GD, Chang JJ, Broering JM, et al. Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor database. J Urol. 2001; 165: 851856.
  • 28
    Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005; 294: 433439.
  • 29
    D'Amico AV, Moul JW, Carroll PR, Sun L, Lubeck D, Chen MH. Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Natl Cancer Inst. 2003; 95: 13761383.
  • 30
    Bastian PJ, Palapattu GS, Lin X, et al. Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res. 2005; 11: 40374043.
  • 31
    Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med. 2003; 348: 24912499.
  • 32
    Bachor R, Kocher F, Gropengiesser F, Reske SN, Hautmann RE. [Positron emission tomography. Introduction of a new procedure in diagnosis of urologic tumors and initial clinical results] (in German). Urologe A. 1995; 34: 138142.