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Preliminary Communication |

PSA Failure Following Definitive Treatment of Prostate Cancer Having Biopsy Gleason Score 7 With Tertiary Grade 5 FREE

Abhijit A. Patel, MD, PhD; Ming-Hui Chen, PhD; Andrew A. Renshaw, MD; Anthony V. D’Amico, MD, PhD
[+] Author Affiliations

Author Affiliations: Departments of Radiation Oncology (Drs Patel and D’Amico) and Pathology (Dr Renshaw), Brigham and Women's Hospital and Dana Farber Cancer Institute (Drs Patel and D’Amico), Boston, Massachusetts; Department of Pathology, Baptist Hospital of Miami, Miami, Florida (Dr Renshaw); and Department of Statistics, University of Connecticut, Storrs (Dr Chen).

More Author Information
JAMA. 2007;298(13):1533-1538. doi:10.1001/jama.298.13.1533.
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Published online

Context In 2005, the International Society of Urologic Pathology consensus conference recommended that men with biopsy Gleason score 3 + 4 or 4 + 3 prostate cancer and tertiary pattern 5 should have their cancer classified as Gleason score 8 or 9, respectively. Yet, the management of men with Gleason score 7 vs 8 or 9 prostate cancer differs.

Objective To compare the prognostic significance of Gleason score 7 with tertiary grade 5 vs other Gleason scores with respect to time to prostate-specific antigen (PSA) failure in men with prostate cancer.

Design, Setting, and Patients From 1989 to 2005, 2370 men with clinical tumor category 1c to 3b, node-negative, and nonmetastatic prostate cancer underwent definitive therapy with surgery or radiation therapy with or without hormonal therapy. A pathologist with expertise in genitourinary cancers assigned Gleason scores to the prostate needle biopsy specimens. Cox regression was used to assess whether a significant association existed between the presence of tertiary grade 5 in men with Gleason score 7 disease and time to recurrence compared with men with Gleason score 7 without tertiary grade 5, Gleason score 5 to 6, or 8 to 10 disease, adjusting for known prognostic factors and treatment.

Main Outcome Measure Time to PSA failure.

Results Men with Gleason score 7 and tertiary grade 5 disease had a significantly shorter time to PSA failure than men with 7 without tertiary grade 5 (median time, 5.0 vs 6.7 years, respectively; adjusted hazard ratio (HR), 0.56; 95% confidence interval [CI], 0.32-0.97; P = .04) or score of 6 or less (median time, 15.4 years; adjusted HR, 0.24; 95% CI, 0.13-0.43; P < .001). However, a significant difference was not observed when these men were compared with men with Gleason score 8 to 10 disease (median time, 5.1 years; adjusted HR, 0.96; 95% CI, 0.54-1.71; P = .90).

Conclusion In this study population, men with prostate cancer having biopsy Gleason score 7 and tertiary grade 5 had a higher risk of PSA-failure when compared with men with Gleason score 7 without tertiary grade 5 and had a comparable risk with men with Gleason score 8 to 10.

Figures in this Article

The widely used Gleason scoring system for the pathological grading of adenocarcinoma of the prostate is based on the architectural patterns of prostatic glands seen at low-power magnification. The system was developed and refined by Donald Gleason based on analysis of more than 4000 prostatectomy specimens from the Veterans Administration Cooperative Urological Research Group series between 1960 and 1975.1,2 Since then, many studies35 have confirmed the prognostic significance of the Gleason score with respect to time to recurrence and death following definitive local therapy.

The Gleason scoring system assigns a grade of 1 to 5 (higher grade being less differentiated) to the predominant pattern and to the second most prevalent pattern in the specimen. The 2 grades are summed to arrive at a final score between 2 and 10 inclusive.6 Although the Gleason scoring formalism does not incorporate a third pattern, the presence of more than 2 Gleason patterns in an individual tumor is widely recognized to occur and many pathologists comment on a tertiary pattern.6,7 In fact, significant heterogeneity has been shown to exist in the patterns of reporting tertiary Gleason grade among pathologists.8 However, the prognostic significance of such a tertiary pattern was not known.

For the situation of biopsy, Gleason score 7 (3 + 4 or 4 + 3) with a tertiary pattern of 5 warrants further investigation as to its prognostic significance. Specifically, there are published studies913 evaluating the implications of tertiary grade 5 within radical prostatectomy specimens, but only 1 study14 with 172 patients examining this situation within biopsy specimens. The existing literature uniformly demonstrates that patients with a prostatectomy Gleason score of 7 and a tertiary pattern of 5 have a significantly shorter time to prostate-specific antigen (PSA) progression than patients with Gleason score 7 tumors without tertiary grade 5 at radical prostatectomy.913 Also, these men with clinically organ–confined prostate cancer and tertiary pattern 5 are more likely to be found to have extraprostatic disease at prostatectomy.9,13

In 2005, the International Society of Urologic Pathology held a consensus conference to address controversial issues surrounding the Gleason grading system.15 Their recommendations regarding tertiary Gleason grade 5 differed depending on the source of the specimen. For radical prostatectomy specimens, they recommended reporting the primary and secondary Gleason patterns, with a comment as to the tertiary pattern. For needle biopsy specimens, they recommended deriving the final Gleason score from the sum of the most prevalent pattern and the highest grade pattern so that tumors with tertiary grade 5 that would have traditionally been reported as Gleason score 3 + 4 or 4 + 3 would be assigned a total score of 8 (3 + 5) and 9 (4 + 5), respectively.

Evidence supporting this recommendation based on time to recurrence following definitive therapy for men with localized or locally advanced prostate cancer are lacking.14 Therefore, in this study, such men are evaluated to determine whether a significant association exists between the presence of tertiary grade 5 in men with Gleason score 7 prostate cancer and time to recurrence compared with men with Gleason score 7 without tertiary grade 5 and men with Gleason score 5 to 6 or 8 to 10 disease adjusting for known prognostic factors.

Patient Characteristics and Treatment

The study cohort comprised 2370 men with clinically tumor (T) category T1c to T3b, node-negative and nonmetastatic adenocarcinoma of the prostate treated between 1989 and 2005 at Harvard-affiliated hospitals (St Anne's Hospital, Brigham and Women's Hospital, and Dana Farber Cancer Institute). Patients were treated with radical prostatectomy (n = 1242), radiation therapy (n = 806), or radiation therapy with 2 months each of neoadjuvant, concurrent, and adjuvant androgen suppression therapy (AST) (n = 322). Patients were excluded if they had undergone radical prostatectomy and received preoperative or postoperative AST, or adjuvant radiation therapy. The study was performed with the approval of the institutional review board of the participating institutions, and each patient signed an informed consent form. All Gleason scores were assigned by a single pathologist (A.A.R.) who has expertise in grading cancers of the genitourinary tract.

In all cases, radical prostatectomy consisted of a radical retropubic prostatectomy with bilateral lymph-node sampling. Radiation therapy was delivered using shaped blocks based on computed tomography−defined volumes transferred onto pelvic plain films prior to 1994, and thereafter, computed tomography-based 3-dimensionl conformal treatment planning was used. A total dose of 70.2 Gy was administered consistently. Adjuvant androgen suppression therapy was achieved by combined blockade with a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) and a nonsteroidal antiandrogen (bicalutamide or flutamide). Injections of leuprolide (7.5 mg/mo) or goserelin (3.6 mg/mo) were given in either 1-month or 3-month formulations. Bicalutamide (50 mg/d) or flutamide (250 mg every 8 hours) were taken orally starting at 1 to 3 days prior to luteinizing hormone-releasing hormone agonist initiation to block the transient testosterone surge.

Follow-up

The median follow-up was 4.2 (interquartile range [IQR], 1.8-6.7) years with censoring occurring at the time of PSA failure, beginning on the date of radical prostatectomy or initiation of other therapy and concluding on March 8, 2005, or the date of death, whichever was earlier. Routine follow-up included a serum PSA measurement followed by a digital rectal examination generally every 3 months for 2 years, then every 6 months for an additional 3 years, and annually thereafter. Prostate-specific antigen recurrence following radiation therapy (with or without AST) was defined as the date at which the PSA level became 2 ng/mL higher than the nadir, according to the 2006 consensus definition of the American Society for Therapeutic Radiology and Oncology.16 Prostate-specific antigen recurrence for surgical patients was defined on the date at which the PSA level became higher than 0.2 ng/mL with a second confirmatory value higher than 0.2 ng/mL.17

Statistical Methods

Time to PSA Failure Analyses. Descriptive statistics were used to define the patient population at baseline. Cox regression univariate and multivariate analyses were performed with the primary end point being time to PSA failure following treatment. Gleason score, tumor category, and treatment modality were analyzed as categorical variables, whereas age and PSA level were considered as continuous variables. For categorical variables, the cut points were defined prior to analyzing the data, according to established strata.4 These categories included Gleason score 6 or less without tertiary grade 4 or 5; 7 without tertiary grade 5; 7 with tertiary grade 5; and 8 to 10; Clinical T category 1c, 2, and 3; treatment with radical prostatectomy, radiation therapy plus AST, or radiation therapy. Baseline groups were Gleason score 7 with tertiary grade 5, clinical T1c category, and treatment group radiation therapy and AST. For all Cox regression analyses, the assumptions of the proportional hazards model were tested and met, and all statistical tests were 2-sided. Adjusted and unadjusted hazard ratios (HRs) for PSA recurrence with the associated 95% confidence intervals (CIs) were calculated for all covariates.18

Propensity Analysis. A propensity analysis was performed to account for biases in treatment effect arising from nonrandom allocation of patients to different treatment groups.19 Propensity analysis required calculation of conditional probabilities for the 3 treatment groups using a multivariate logistic regression model. Two of the propensity scores (for radical prostatectomy and radiation therapy) were then used in the Cox regression model.

Estimates of PSA failure stratified by Gleason Score. For the purpose of illustration, estimates of time to PSA recurrence following treatment and stratified by the categorical covariate of Gleason score were displayed and these estimates were made using the method of Kaplan and Meier.20 These estimates were compared using a log-rank test,21 and an adjustment for multiple comparisons was made with the use of a Bonferroni correction. The median time to PSA recurrence was calculated using the Kaplan-Meier estimator and described. A 2-sided P value of .05 or less was considered statistically significant. Analyses were performed using SAS version 9.1.3 (SAS Institute Inc, Cary, NC).

Clinical Characteristics of the Study Cohort

As shown in Table 1, the median age of the 2370 men who comprised the study cohort at the time of initial therapy was 66 (IQR, 59-72) years. The median PSA level was 7.4 (IQR, 5.1-12) ng/mL. The distribution of the men by Gleason score was 1059 (45%) with Gleason score 6 or less, 999 (42%) with Gleason score 7 without tertiary grade 5, 36 (1.5%) with Gleason score 7 with tertiary grade 5, and 276 (12%) with Gleason score 8 to 10.

Table Graphic Jump LocationTable 1. Baseline Clinical Characteristics of Study Cohorta
Time to PSA Failure

The median time to PSA failure was 5.0 years for men with Gleason score 7 and tertiary grade 5 disease, 5.1 years for men with Gleason score 8 to 10, 6.7 years for men with Gleason score 7 without tertiary grade 5, and 15.4 years for men with Gleason score 6 or less. As shown in Table 2, after adjusting for known prognostic factors including the PSA level, age, tumor category, and therapy received and including a propensity score in the multivariate model to further adjust for any potential bias associated with treatment selection, Cox regression multivariate analysis revealed that men with biopsy Gleason score 7 and a tertiary grade 5 component had a significantly shorter time to PSA failure than men with biopsy Gleason score 7 without tertiary grade 5 (adjusted HR, 0.56: 95% CI, 0.32-0.97; P = .04) and men with biopsy Gleason score 6 or less (adjusted HR, 0.24; 95% CI, 0.13-0.43; P < .001). However, the time to PSA failure was not significantly different between men with biopsy Gleason score 7 and tertiary grade 5 and Gleason score 8 to 10 (adjusted HR, 0.96; 95% CI, 0.54-1.71; P = .90) disease. Other clinical factors that were significantly associated with time to PSA failure on multivariate analysis included the PSA level at diagnosis (adjusted HR, 1.02; 95% CI, 1.01-1.02; P < .001), treatment with radiation therapy (adjusted HR, 3.02; 95% CI, 2.32-3.93; P < .001), and tumor category T3 (adjusted HR, 2.42; 95% CI, 1.57-3.73; P < .001). Age (P = .83), treatment with radical prostatectomy (P = .26), and tumor category T2 (P = .06) were not significantly associated with time to PSA failure. Detailed in Table 3 are the results of the Cox regression analysis of these covariates separated by treatment group (radical prostatectomy, radiation therapy, or radiation therapy plus AST).

Table Graphic Jump LocationTable 2. Unadjusted and Adjusted Hazard Ratios of Clinical Factors Describing the Risk of Prostate-Specific Antigen Recurrence Following Definitive Therapy
Table Graphic Jump LocationTable 3. Adjusted Hazard Ratios of Clinical Factors Describing the Risk of PSA Recurrence Stratified by Treatment Modality
Estimates of PSA Failure Stratified by Gleason Score

After a median follow-up of 4.2 (IQR, 1.8-6.7) years, there were 613 PSA recurrences. As shown in the Figure, estimates of PSA-recurrence were significantly higher among men with biopsy Gleason score 7 with tertiary grade 5 than among men with Gleason score 7 without tertiary grade 5 (P = .01) and men with Gleason score 6 (P < .001) but were not significantly different from men with Gleason score 8 to 10 (P = .57). Specifically, estimates at 5 years following treatment were 21% (95% CI, 18% to 25%) for men with Gleason score 6 or less, 33% (95% CI, 29% to 37%) for men with Gleason score 7 without tertiary grade 5, 56% (95% CI, 37% to 77%) for men with Gleason score 7 with tertiary grade 5, and 50% (95% CI, 43% to 57%) for men with Gleason score 8 to 10 disease.

Figure. Estimates of Prostate-Specific Antigen (PSA) Recurrence Following Radical Prostatectomy or External Beam Radiation Therapy With or Without Androgen Suppression Therapy
Graphic Jump Location

Gleason scores 6 or less vs 7 with tertiary grade 5, P < .001; 6 or less vs 7 without tertiary grade 5, P < .001; 7 without tertiary grade 5 vs 7 with tertiary grade 5, P = .011; and 7 with tertiary grade 5 vs 8 to 10, P = .57. After applying the Bonferroni correction, P values <.0125 are significant.

In the present study, we evaluated the time to recurrence in 2370 men treated with radical prostatectomy, or radiation therapy with or without AST. We found that men with biopsy Gleason score 7 prostate cancer and tertiary grade 5 had a time to PSA recurrence that was significantly shorter than men with Gleason score 7 cancer without tertiary grade of 5 and men with Gleason score 6 or less but not significantly different from men with Gleason score 8 to 10 disease after adjusting for known prognostic factors.

If these findings are validated by additional studies in other populations, they may affect the management of care for men with Gleason score 7 prostate cancer for which the currently practiced management standards include dose-escalated radiation therapy including prostate brachytherapy with or without supplemental radiation therapy,2224 radiation therapy and short course AST,25,26 or radical prostatectomy. Specifically, given the time to recurrence (Figure), management options for men with Gleason score 7 who also have tertiary grade 5 disease could include treatments that are the current standards of care for men with Gleason 8 to 10 prostate cancer. These standards of care based on the results of randomized trials2528 include radiation therapy and short-25,26 or extended-course AST,27,28 or radical prostatectomy with the expectation that further therapy may be needed postoperatively depending on the final pathology findings of the radical prostatectomy and postoperative PSA level. Moreover, men with Gleason score 7 and tertiary grade 5 might be considered for enrollment in randomized trials for which men with Gleason score 8 to 10 disease are eligible.

A potential limitation of our study is the median follow-up time of 4.2 years not permitting an assessment of the time to prostate cancer specific and all-cause mortality end points. The sample size of our study, while large, was not large enough to provide the statistical power to distinguish the effect of tertiary grade 5 with Gleason 7 disease among various treatment modalities. Although a trend toward significance is seen in the subsets, true statistical significance only emerges when the data are pooled. The power of the study is limited by the sample size of men with Gleason score 7 and tertiary grade 5 disease. Specifically, this limited power is reflected in the wide 95% CI of the HR comparing the risk of PSA failure in men with Gleason score 7 with or without tertiary grade 5. A much larger data set would be required to demonstrate significant differences among the treatment subgroups because of the low prevalence of tertiary grade 5 in biopsy specimens. However, the study had consistent Gleason scoring performed by a single pathologist who has expertise in cancers of the genitourinary tract, a large sample size and significant number of PSA failures and included all treatment modalities that are currently considered standard for men with localized or locally advanced prostate cancer with the exception of prostate brachytherapy.

In conclusion, men with biopsy Gleason score 7 prostate cancer and tertiary grade 5 disease may have a risk of PSA failure following definitive therapy comparable with men with biopsy Gleason score 8 to 10 disease. These findings warrant further investigation in additional studies and different populations.

Corresponding Author: Abhijit A. Patel, MD, PhD, Department of Radiation Oncology, Brigham and Women's Hospital, 75 Francis St, L-2 Level, Boston, MA 02115 (aapatel@partners.org).

Author Contributions: Dr D’Amico had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Patel, Renshaw, D’Amico.

Acquisition of data: Renshaw.

Analysis and interpretation of data: Patel, Chen, Renshaw, D’Amico.

Drafting of the manuscript: Patel, D’Amico.

Critical revision of the manuscript for important intellectual content: Patel, Chen, Renshaw, D’Amico.

Statistical analysis: Chen, D’Amico.

Study supervision: D’Amico.

Financial Disclosures: None reported.

Funding/Support: There was no external financial support for this study. Dr Chen's research was partially supported by National Institutes of Health grants GM 70335 and CA 74015.

Additional Contributions: We thank Marian Loffredo, RN, at Brigham and Women's Hospital for assistance with preparation of materials for institutional board review. She received no compensation for her assistance.

Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging.  J Urol. 1974;111(1):58-64
PubMed
Mellinger GT, Gleason D, Bailar J III. The histology and prognosis of prostatic cancer.  J Urol. 1967;97(2):331-337
PubMed
Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin tables) for the new millennium.  Urology. 2001;58(6):843-848
PubMed   |  Link to Article
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(11):969-974
PubMed   |  Link to Article
Kattan MW, Zelefsky MJ, Kupelian PA.  et al.  Pretreatment nomogram that predicts 5-year probability of metastasis following three-dimensional conformal radiation therapy for localized prostate cancer.  J Clin Oncol. 2003;21(24):4568-4571
PubMed   |  Link to Article
Gleason DF. Histologic grading of prostate cancer: a perspective.  Hum Pathol. 1992;23(3):273-279
PubMed   |  Link to Article
Aihara M, Wheeler TM, Ohori M.  et al.  Heterogeneity of prostate cancer in radical prostatectomy specimens.  Urology. 1994;43(1):60-66
PubMed   |  Link to Article
Egevad L, Allsbrook WC, Epstein JI. Current practice of Gleason grading among genitourinary pathologists.  Hum Pathol. 2005;36(1):5-9
PubMed   |  Link to Article
Pan CC, Potter SR, Partin AW, Epstein JI. The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system.  Am J Surg Pathol. 2000;24(4):563-569
PubMed   |  Link to Article
Rasiah KK, Stricker PD, Haynes AM.  et al.  Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma.  Cancer. 2003;98(12):2560-2565
PubMed   |  Link to Article
Hattab EM, Koch MO, Eble JN, Lin H, Cheng L. Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in patients with Gleason score 7 prostatic adenocarcinoma.  J Urol. 2006;175(5):1695-1699
PubMed   |  Link to Article
Sim HG, Telesca D, Culp SH.  et al.  Tertiary Gleason pattern 5 in Gleason 7 prostate cancer predicts pathologic parameters and biochemical recurrence [Abstract 470].  J Urol. 2007;177(4):(suppl)  157
Mosse CA, Magi-Galluzzi C, Tsuzuki T, Epstein JI. The prognostic significance of tertiary Gleason pattern 5 in radical prostatectomy specimens.  Am J Surg Pathol. 2004;28(3):394-398
PubMed   |  Link to Article
Trpkov K, Chan M, Kmet L, Yilmaz A. Significance of tertiary Gleason grade 5 on needle biopsy [abstract].  Mod Pathol. 2007;20:(suppl 2s)  180A-181A
Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL.ISUP Grading Committee.  The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.  Am J Surg Pathol. 2005;29(9):1228-1242
PubMed   |  Link to Article
Roach M III, Hanks G, Thames H Jr.  et al.  Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.  Int J Radiat Oncol Biol Phys. 2006;65(4):965-974
PubMed   |  Link to Article
Cookson MS, Aus G, Burnett AL.  et al.  Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.  J Urol. 2007;177(2):540-545
PubMed   |  Link to Article
Klein JP, Moeschberger MLSurvival AnalysisNew York, NY: Springer-Verlag; 1997:96-100, 229-268
Newgard CD, Hedges JR, Arthur M, Mullins RJ. Advanced statistics: the propensity score—a method for estimating treatment effect in observational research.  Acad Emerg Med. 2004;11(9):953-961
PubMed
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations.  J Am Stat Assoc. 1958;53:457-481
Link to Article
Peto R, Peto J. Asymptotically efficient rank invariant test procedures.  J R Stat Soc [Ser A]. 1972;135:185-206
Grimm PD, Blasko JC, Sylvester JE, Meier RM, Cavanagh W. 10-year biochemical (prostate-specific antigen) control of prostate cancer with (125)I brachytherapy  Int J Radiat Oncol Biol Phys. 2001;51(1):31-40
PubMed   |  Link to Article
Pollack A, Zagars GK, Smith LG.  et al.  Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer.  J Clin Oncol. 2000;18(23):3904-3911
PubMed
Zietman AL, DeSilvio ML, Slater JD.  et al.  Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial.  JAMA. 2005;294(10):1233-1239
PubMed   |  Link to Article
D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial.  JAMA. 2004;292(7):821-827
PubMed   |  Link to Article
Denham JW, Steigler A, Lamb DS.  et al.  Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial.  Lancet Oncol. 2005;6(11):841-850
PubMed   |  Link to Article
Bolla M, Collette L, Blank L.  et al.  Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.  Lancet. 2002;360(9327):103-106
PubMed   |  Link to Article
Hanks GE, Pajak TF, Porter A.  et al.  Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.  J Clin Oncol. 2003;21(21):3972-3978
PubMed   |  Link to Article

Figures

Figure. Estimates of Prostate-Specific Antigen (PSA) Recurrence Following Radical Prostatectomy or External Beam Radiation Therapy With or Without Androgen Suppression Therapy
Graphic Jump Location

Gleason scores 6 or less vs 7 with tertiary grade 5, P < .001; 6 or less vs 7 without tertiary grade 5, P < .001; 7 without tertiary grade 5 vs 7 with tertiary grade 5, P = .011; and 7 with tertiary grade 5 vs 8 to 10, P = .57. After applying the Bonferroni correction, P values <.0125 are significant.

Tables

Table Graphic Jump LocationTable 1. Baseline Clinical Characteristics of Study Cohorta
Table Graphic Jump LocationTable 2. Unadjusted and Adjusted Hazard Ratios of Clinical Factors Describing the Risk of Prostate-Specific Antigen Recurrence Following Definitive Therapy
Table Graphic Jump LocationTable 3. Adjusted Hazard Ratios of Clinical Factors Describing the Risk of PSA Recurrence Stratified by Treatment Modality

References

Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging.  J Urol. 1974;111(1):58-64
PubMed
Mellinger GT, Gleason D, Bailar J III. The histology and prognosis of prostatic cancer.  J Urol. 1967;97(2):331-337
PubMed
Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin tables) for the new millennium.  Urology. 2001;58(6):843-848
PubMed   |  Link to Article
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(11):969-974
PubMed   |  Link to Article
Kattan MW, Zelefsky MJ, Kupelian PA.  et al.  Pretreatment nomogram that predicts 5-year probability of metastasis following three-dimensional conformal radiation therapy for localized prostate cancer.  J Clin Oncol. 2003;21(24):4568-4571
PubMed   |  Link to Article
Gleason DF. Histologic grading of prostate cancer: a perspective.  Hum Pathol. 1992;23(3):273-279
PubMed   |  Link to Article
Aihara M, Wheeler TM, Ohori M.  et al.  Heterogeneity of prostate cancer in radical prostatectomy specimens.  Urology. 1994;43(1):60-66
PubMed   |  Link to Article
Egevad L, Allsbrook WC, Epstein JI. Current practice of Gleason grading among genitourinary pathologists.  Hum Pathol. 2005;36(1):5-9
PubMed   |  Link to Article
Pan CC, Potter SR, Partin AW, Epstein JI. The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system.  Am J Surg Pathol. 2000;24(4):563-569
PubMed   |  Link to Article
Rasiah KK, Stricker PD, Haynes AM.  et al.  Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma.  Cancer. 2003;98(12):2560-2565
PubMed   |  Link to Article
Hattab EM, Koch MO, Eble JN, Lin H, Cheng L. Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in patients with Gleason score 7 prostatic adenocarcinoma.  J Urol. 2006;175(5):1695-1699
PubMed   |  Link to Article
Sim HG, Telesca D, Culp SH.  et al.  Tertiary Gleason pattern 5 in Gleason 7 prostate cancer predicts pathologic parameters and biochemical recurrence [Abstract 470].  J Urol. 2007;177(4):(suppl)  157
Mosse CA, Magi-Galluzzi C, Tsuzuki T, Epstein JI. The prognostic significance of tertiary Gleason pattern 5 in radical prostatectomy specimens.  Am J Surg Pathol. 2004;28(3):394-398
PubMed   |  Link to Article
Trpkov K, Chan M, Kmet L, Yilmaz A. Significance of tertiary Gleason grade 5 on needle biopsy [abstract].  Mod Pathol. 2007;20:(suppl 2s)  180A-181A
Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL.ISUP Grading Committee.  The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.  Am J Surg Pathol. 2005;29(9):1228-1242
PubMed   |  Link to Article
Roach M III, Hanks G, Thames H Jr.  et al.  Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.  Int J Radiat Oncol Biol Phys. 2006;65(4):965-974
PubMed   |  Link to Article
Cookson MS, Aus G, Burnett AL.  et al.  Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.  J Urol. 2007;177(2):540-545
PubMed   |  Link to Article
Klein JP, Moeschberger MLSurvival AnalysisNew York, NY: Springer-Verlag; 1997:96-100, 229-268
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