Original Study
Greatest Percentage of Involved Core Length and the Risk of Death From Prostate Cancer in Men With Highest Gleason Score ≥ 7

This work was presented as a poster presentation at the 10th annual American Society of Clinical Oncology Genitourinary Cancers Symposium; January 30 to February 1, 2014; San Francisco, CA.
https://doi.org/10.1016/j.clgc.2014.01.006Get rights and content

Abstract

Introduction/Background

Men with highest GS ≥ 7 and a differing, lower GS core (ComboGS) have decreased PC-specific mortality (PCSM) risk after RT or RT and androgen deprivation therapy (ADT). Whether the greatest percentage of involved core length (GPC) modulates this risk is unknown.

Patients and Methods

Men with GS ≥ 7 PC (n = 333) consecutively treated between December 1989 and July 2000 using RT (n = 268; 80%) or RT and 6 months of ADT (n = 65; 20%) comprised the study cohort. The GPC was calculated using biopsy core and tumor lengths. We used competing risks regression to assess whether increasing GPC was associated with increased PCSM risk in men with or without ComboGS adjusting for risk group, age, and treatment.

Results

After a median follow-up of 5.36 years (interquartile range, 3.22-7.61 years), 92 (28%) men died, 28 (30%) of PC. Increasing GPC was significantly associated with increased risk of PCSM (adjusted hazard ratio, 1.02; 95% confidence interval, 1.01-1.03; P = .005). Men with GPC ≥ 50% versus < 50% had significantly greater PCSM estimates when ComboGS was present (P < .001) versus absent (P = .55). Of the 127 men with ComboGS and GPC < 50%, 83% were treated with RT alone and 2 PC deaths were observed; neither in men with GS 7 and favorable intermediate-risk PC.

Conclusion

Men treated with RT for ComboGS, GPC < 50%, GS 7, and favorable intermediate-risk PC have a very low risk of early PCSM. The RTOG 0815 trial will establish whether ADT is necessary to optimize curability in these men.

Introduction

The Gleason score (GS) is a validated prognostic factor significantly associated with prostate cancer (PC)-specific mortality (PCSM) in men with clinically localized or locally advanced PC undergoing conservative or curative management.1, 2, 3, 4, 5, 6 Specifically, the risk of PCSM and all cause mortality can be stratified using the conventional GS cut points of 8 to 10, 7, and 6. Multiple studies have established the prognostic utility of the GS after adjustment for known risk factors including prostate-specific antigen (PSA) level, clinical tumor category (T-category), and percentage of positive biopsy cores (PPB).1, 7, 8, 9, 10 Recently, investigators have identified a novel prognostic factor, ComboGS, defined as the presence of at least 1 differing, lower GS core in men whose transrectal ultrasound-guided prostate needle biopsy (TRUS PNB) shows a highest GS ≥ 7. ComboGS has been associated with a reduced risk of upgrading at time of radical prostatectomy (RP).11, 12 Specifically, the presence versus absence of ComboGS was associated with an adjusted odds ratio for upgrading of 0.18 (95% confidence interval [CI], 0.04-0.76; P = .02) in one study.11 In addition, men with highest GS ≥ 7 and ComboGS present also have a decreased risk of PCSM after treatment with radiation therapy (RT) or RT and androgen deprivation therapy (ADT) (adjusted hazard ratio [AHR], 0.40; 95% CI, 0.19-0.85; P = .017).13

Multiple studies suggest that biopsy core tumor volume (BCTV) in addition to PPB correlates with tumor grade and stage, and is associated with the risk of biochemical recurrence.14, 15, 16, 17, 18 The greatest percentage of cancer involvement in a single biopsy core (GPC) is a commonly reported BCTV metric.15 Significant controversy exists however, among genitourinary pathologists regarding its most appropriate measurement.15, 19, 20, 21 Nevertheless, because of the more favorable prognosis of men with ComboGS, it would be clinically relevant to ascertain whether a BCTV metric has prognostic value after RT in men with ComboGS to evaluate if a subset of men can be identified in whom de-escalated treatment strategies might be sufficient to avoid PCSM, thereby limiting treatment-associated toxicities.12, 13, 22

Therefore, the purpose of the current study was to evaluate the effect of the GPC on the risk of PCSM in men with highest GS ≥ 7 with or without ComboGS, adjusting for risk group, age, and treatment received.1

Section snippets

Patient Population and Treatment

The study cohort consisted of 333 consecutive men with GS ≥ 7 PC treated definitively between December 1989 and July 2000 with either RT to a total dose of 70 Gy (n = 268; 80.5%) or RT and 6 months of ADT (n = 65; 19.5%) at St Anne's Hospital (Fall River, MA). All men who received ADT did so as part of a randomized clinical trial investigating the addition of 6 months of ADT to RT in intermediate- and high-risk PC (NCT 00116220). Patients underwent TRUS PNB with a median of 6 cores

Distribution of Clinical Characteristics at Baseline Stratified According to the Presence or Absence of ComboGS

As shown in Table 1, men in whom ComboGS was present compared with absent had a lower median PSA (9.43 ng/mL vs. 13.30 ng/mL; P = .001) and a trend toward a lower median GPC (50% vs. 60%; P = .07). There were no other significant differences in the distribution of known prognostic factors for PCSM, NCCN risk group, or in treatment received.

Competing Risks Regression

After a median follow-up of 5.36 years (IQR, 3.22-7.61 years) 92 (27.6%) men died, 28 (30.4%) of PC. As shown in Table 2, after adjusting for D'Amico risk

Discussion

Many investigators have previously studied the use of biopsy surrogates of prostate tumor volume for prediction of prognosis after RP or RT. With the exception of number of positive cores and PPB, limited data exist supporting the utility of these measures.20 However, consensus exists that reporting of additional, more detailed measures is warranted, most commonly percent core involvement or length of cancer. To our knowledge, only 1 previous study has investigated the prognostic value of the

Conclusion

In this study of men with GS ≥ 7 PC undergoing RT with or without ADT, distinct groups of men with varied prognoses were defined based on clinical factors available at time of presentation. Specifically, after a median follow-up of approximately 5.4 years, the 6-year PCSM estimate was only approximately 1% in men in whom ComboGS was present and GPC < 50%, compared with 10% to 24% when either ComboGS was present and GPC ≥ 50% or ComboGS was absent irrespective of the GPC.

Only 2 PC deaths were

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgments

The authors acknowledge Brittany Loffredo for providing the additional fields in the database that permitted the current analysis.

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