Optimizing patient selection for dose escalation techniques using the prostate-specific antigen level, biopsy gleason score, and clinical T-stage

doi:10.1016/S0360-3016(99)00303-X

International Journal of Radiation OncologyBiologyPhysics

Volume 45, Issue 5, 1 December 1999, Pages 1227-1233

https://doi.org/10.1016/S0360-3016(99)00303-X Get rights and content

Abstract

Purpose: Ideal candidates for 3D dose escalation conformal radiation or external beam + implant therapy are identified on the basis of the prostate-specific antigen (PSA) level, biopsy Gleason score, and the 1992 American Joint Commission Cancer (AJCC) clinical T-stage.

Methods and Materials: The pathologic findings of 1742 men with clinical stage T1c,2 prostate cancer managed with a radical prostatectomy (RP) between 1990 and 1998 were subjected to a logistic regression multivariable analysis. The endpoints examined included pathologic organ–confined (OC), specimen-confined (SC), and margin (M) or seminal vesicle (SV) positive disease. SC disease was defined as extracapsular extension (ECE) with a negative surgical margin. The clinical factors tested included PSA level, biopsy Gleason score, and the 1992 AJCC clinical T-stage. PSA failure–free (bNED) survival was calculated according to the method of Kaplan and Meier.

Results: Significant negative predictors of pathologic OC–disease or positive predictors of M⁺ or SV⁺ disease included a PSA > 10 ng/ml (p < 0.0001), biopsy Gleason score ≥7 (p ≤ 0.0004), and ≥ T2b disease (p ≤ 0.03). Only biopsy Gleason score 7 (p = 0.0006) and PSA 10–15 ng/ml (p = 0.04) were significant predictors of SC disease. The estimates of 5-year bNED survival were 80%, 62%, and 35% (p < 0.0001) for patients having a low, intermediate, or high likelihood of having M⁺ or SV⁺ disease respectively.

Conclusions: Patients most likely to derive a survival benefit from the improved local control possible using dose escalation techniques were those who had both a low risk of having occult micrometastatic disease (<25% M⁺ or SV⁺) and a reasonable likelihood of remaining disease-free after RP (>50% 5-year bNED). These patients included those having T1c, 2a, PSA > 10–15 ng/ml, and biopsy Gleason ≤6 or T1c, 2a, 2b, PSA ≤ 10 ng/ml, and biopsy Gleason ≤ 7 prostate cancer.

Introduction

Data from the surgical literature 1, 2 have suggested that the cancer-specific survival after radical prostatectomy (RP) decreases as one advances from pathologic organ–confined to specimen-confined (extracapsular extension [ECE] with negative surgical margins) to positive-margin, seminal vesicle–positive, and finally lymph node–positive disease. These decrements in cancer-specific survival could be due to local failure that in time metastasizes and becomes a distant failure. However, a significant proportion of these deaths are likely due to the increasing incidence of occult distant micrometastatic disease present in men with a more advanced pathologic stage at the time of the RP.

Therefore, selecting the patient likely to derive a survival benefit from the use of dose escalation radiotherapy techniques would have two requirements. First, the probability of seminal vesicle invasion, margin-positive or lymph-node–positive disease would need to be low in order to minimize the risk of occult micrometastatic disease. Second, there would need to be a high likelihood that radical local therapy could ablate the entire volume of cancer. The likelihood of success in this regard may be approximated from the prostate-specific antigen (PSA) failure–free (bNED) survival after RP. Identifying these patients prior to therapy, on the basis of the readily available pretreatment prognostic factors was the goal of this study.

Section snippets

Patient population

Seventeen hundred and forty-two men treated with a RP and bilateral pelvic lymph node dissection at the Hospital of the University of Pennsylvania (HUP) or the Brigham and Women’s (B&W) Hospital between 1990 and 1998 who had PSA detected or clinically palpable prostate cancer comprised the study population. Table 1 lists the preoperative clinical and postoperative pathological characteristics of the 1742 study patients.

Preoperative staging

In all cases, staging evaluation included a history and physical examination

Clinical predictors of pathologic stage

The significant negative predictors of pathologic organ–confined disease were analogous to the positive predictors of positive margins or seminal vesicle invasion. These clinical predictors included a PSA > 10 ng/ml (p < 0.0001), biopsy Gleason score ≥ 7 (p ≤ 0.0004), and ≥ T2b disease (p ≤ 0.03). Only biopsy Gleason score 7 (p = 0.0006) and PSA > 10–15 ng/ml (p = 0.04) were significant predictors of specimen-confined disease. Table 2 lists the complete set of p-values for the logistic

Discussion

Retrospective comparisons of patients managed with 3D dose escalation conformal external beam RT 8, 9, 10 or external beam + interstitial implant boost 11, 12 versus conventional-dose external beam RT have reported statistically significant improvements in bNED survival rates. One report from Hanks and colleagues (8) has suggested an improvement in overall survival for men treated with 3D dose escalation RT versus historical controls treated with external beam RT to conventional dose. While

Conclusion

Patients most likely to derive a survival benefit from the improved local control possible using dose escalation techniques in this study were those who had both a low risk of having occult micrometastatic disease (<25% M⁺ or SV⁺) and a reasonable likelihood of remaining disease-free after RP (>50% 5-year bNED). These patients included those having T1c, 2a, PSA > 10–15 ng/ml, and biopsy Gleason ≤6 or T1c, 2a, 2b, PSA ≤ 10 ng/ml, and biopsy Gleason ≤7 prostate cancer.

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One hundred five patients consecutively treated between 1998 and 2004 are reported. All patients were treated with HDR boost with lr 192 (5.5–7.0 Gy), based upon postimplant CT three-dimensional treatment planning using an in-house treatment plan optimization algorithm. Three-dimensional conformal external beam radiotherapy (45–50.4 Gy) was also administered 3 weeks after the HDR procedure. Toxicity was measured using National Cancer Institutes Common Toxicity Criteria and International Prostate Symptom Score indices.
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$Purpose$ : Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of prostate cancer that should receive RT at any point in the evolution of the illness.
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2001, International Journal of Radiation Oncology Biology Physics
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One exception was found in patients with at least one poor prognostic factor (i.e., pretreatment PSA >10 ng/mL, T Stage 3–4, and Gleason score 7–10), who appeared to benefit the most from dose escalation, most likely because they had both a low risk of micrometastatic disease and were likely to remain disease-free after treatment (Table 6). Recent studies on patient selection for dose escalation suggest similar findings (31). M.D. Anderson recently published preliminary results of the only randomized trial to compare 3D-CRT to SRT in prostate cancer patients (32).
$Purpose:$ To discuss the assumptions behind and current clinical evidence on three-dimensional conformal radiation therapy (3D-CRT) and dose escalation in the treatment of prostate cancer.
$Methods:$ We first define 3D-CRT in comparison to standard radiation therapy and discuss the assumptions on which the technology of 3D-CRT and dose escalation are based. We then examine the evidence on the benefits and limitations from the current most commonly cited studies on dose-escalation trials to treat prostate cancer.
$Results:$ The assumption that 3D-CRT can provide a tighter margin around the tumor area to allow for dose escalation is not yet proven by studies that show continual difficulty in defining the planning treatment volume because of extrinsic and intrinsic difficulties, such as imaging variabilities and patient and organ movement. Current short-term dose-escalation studies on the use of 3D-CRT to treat prostate cancer are limited in their ability to prove that increasing dose improves survival and does not incur potential long-term complications to normal tissue.
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Clinical InvestigationsOptimizing patient selection for dose escalation techniques using the prostate-specific antigen level, biopsy gleason score, and clinical T-stage

Abstract

Introduction

Section snippets

Patient population

Preoperative staging

Clinical predictors of pathologic stage

Discussion

Conclusion

J Urol

J Urol

J Urol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical Investigations
Optimizing patient selection for dose escalation techniques using the prostate-specific antigen level, biopsy gleason score, and clinical T-stage