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The Prostate 37:195–206 (1998)
Review Article
Update on the Treatment of Prostate Cancer
With External Beam Irradiation
Eric M. Horwitz,* Alexandra L. Hanlon, and Gerald E. Hanks
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
BACKGROUND. We review the recent changes in the radiotherapeutic management of
clinically localized prostate cancer, including the implementation of three-dimensional (3-D)
conformal radiation therapy (3DCRT), biochemical disease-free survival (bNED control) using
conventional and 3DCRT techniques, and the morbidity of these treatment strategies.
METHODS. The components of 3DCRT are discussed, including patient immobilization, 3-D
treatment planning, multileaf collimation, and electronic portal imaging. bNED control rates
from institutions using conventional and 3DCRT techniques are compared. The gastrointestinal (GI) and genitourinary (GU) morbidity from prospective trials using conventional doses
of radiation are compared to data from 3DCRT series. bNED control rates stratified by pretreatment prostate-specific antigen (PSA) are compared between surgical and radiation series.
RESULTS. bNED control rates (3–5 years) for patients treated with conventional and 3DCRT
techniques ranged from 44–70% and 30–72% with pretreatment PSA levels 4–10 and 10–20,
respectively. Although direct comparisons are difficult between treatment modalities, no
difference in bNED control stratified by pretreatment PSA was observed between surgical and
radiation patients.
CONCLUSIONS. Patients with clinically localized prostate cancer treated with 3DCRT demonstrate durable bNED control at 5 years. Conformal radiation techniques, multileaf collimation, electronic portal imaging, and patient immobilization have reduced acute and chronic GI
and GU morbidity while allowing safe dose escalation in an effort to further improve local
control and overall survival. Prostate 37:195–206, 1998. © 1998 Wiley-Liss, Inc.
INTRODUCTION
The American Cancer Society estimates there will
be 210,000 new cases of prostate cancer diagnosed in
the United States in 1997 [1,2]. For those patients with
clinically localized disease, several options for treatment exist, including observation [3], surgery [4], radiation therapy [5], or hormonal manipulation [6]. External beam radiation therapy has been a mainstay in
the management of prostate cancer over the last 35
years and continues to treat 29% of all patients receiving definitive therapy [7].
The development of the prostate-specific antigen
(PSA) test and its use as a screening tool has increased
the number of patients diagnosed and treated with
early-stage disease. More importantly, pretreatment
PSA levels have been shown to be the strongest independent predictor of treatment outcome after both
surgery and radiation, and a rising posttreatment PSA
level indicates failure many years before disease becomes clinically detected [8–10]. Proper use of pre© 1998 Wiley-Liss, Inc.
treatment categorization of disease and serial posttreatment PSA levels allow an accurate and meaningful assessment of various treatment modalities.
The development and clinical testing of threedimensional (3-D) conformal radiation therapy
(3DCRT) since 1989 has demonstrated clearly that this
technology results in improved outcome compared to
conventional treatment techniques [5,11,12]. The use
of 3DCRT enables the safe delivery of higher doses of
radiation to the prostate with reduced morbidity, especially in patients with pretreatment PSA levels
greater than 10 ng/ml [13]. The purpose of this communication is to review the current results with external beam radiation therapy (RT), including results
with 3DCRT, and make limited comparisons with results from prostatectomy series.
*Correspondence to: Eric M. Horwitz, M.D., Department of Radiation Oncology, Fox Chase Cancer Center, 7701 Burholme Ave.,
Philadelphia, PA 19111. E-mail: EM Horwitz@fccc.edu
Received 22 October 1997; Accepted 7 May 1998
196
Horwitz et al.
Fig. 1. Anterior digitally reconstructed radiograph (DRR)
treatment portal for 3DCRT.
RESULTS
3DCRT vs. Conventional Technique
Three-dimensional conformal radiation therapy is
external beam irradiation in which the radiation treatment volume closely matches the macroscopic and microscopic tumor volume. The goal of 3DCRT is to better delineate and immobilize the target (prostate), allowing decreased treatment margins and thereby
delivering higher doses of radiation to the prostate.
This minimizes the volume of normal tissue receiving
a clinically significant radiation dose and reduces the
probability of normal tissue complications. This is accomplished by 1) immobilizing the patient in the treatment position with a posterior body cast to reduce
day-to-day patient motion and positioning error
[14,15]; 2) reconstruction of the prostate (target) in
three dimensions from a CT scan done with the patient in the treatment cast; 3) directing multiple beams
at the target that are shaped to conform to the shape of
the target from each beam’s eye view (BEV) [16]; 4)
using treatment-planning computers with dosimetric
algorithms which allow the calculation of dose in
three dimensions; 5) using electronic portal imaging
devices which allow real-time visualization of the
treatment fields to assure proper patient position [17];
and 6) using multileaf collimation (MLC) in the place
of cerrobend blocking [18–20]. With MLC, the treatment field can be adjusted, accommodating both isocenter and field margin changes without moving the
patient and introducing additional error. Figures 1
and 2 illustrate conformal treatment portals for an anterior and lateral view, including 1 cm of normal tissue
margin around the prostate gland.
Our 3-D treatment technique has previously been
reported [13]. To summarize briefly, the patient first
undergoes a treatment-planning CT while immobilized in a half-body alpha cradle from the waist to the
knees. CT slices 3 mm thick are obtained from the top
of the sacro-iliac joints through the bottom of the obturator foramen. The gross tumor volume is defined as
the entire prostate according to the ICRU 50 report
[21]. The seminal vesicles, and periprostatic, obturator, internal, and external iliac lymph nodes are also
contoured. Treatment field size and dose guidelines at
Fox Chase depend on pretreatment PSA, Gleason
score, and clinical T stage. A contour 1.2 cm superior
to the apex of the urethrogram contrast defines the
inferior most portion of the prostate. The planning target volume (PTV) is defined as the prostate plus 1–1.5
cm in all directions. Conformal blocks are placed
around the PTV in all directions, using BEV visualization. Doses range from 68–75 Gy, but currently remain
at 70–72 Gy. Since 1993, lateral blocking has been
added for the final 10 Gy to reduce the dose to the
anterior rectal wall [22].
One endpoint for comparing outcomes between
these two RT techniques is to measure 12-month PSA
response. The 12-month PSA response was analyzed
for 260 patients treated at Fox Chase to determine if
External Beam Irradiation of Prostate Cancer
197
Fig. 2. Lateral digitally reconstructed radiograph
(DRR) treatment portal for
3DCRT.
conformal treatment techniques were superior to conventional techniques. Patients were divided into two
groups based on treatment technique (conventional
vs. conformal) and 12-month PSA response determined for each group using two definitions (PSA 艋1.5
ng/ml and PSA 艋4.0 ng/ml). The median total dose
was the same for both groups (70 Gy). The patients
treated with 3DCRT had a statistically significant improvement in the 12-month PSA response compared
to the group of patients treated with conventional
techniques using both definitions (Table I) [11].
Biochemical Freedom From Disease
(bNED Control)
Table II shows bNED control rates stratified by pretreatment PSA for patients treated with conventional
doses of external beam RT from several institutions
from the PSA era. Direct comparison of results is difficult due to different definitions of bNED control
used, unequal distribution of critical prognostic factors between series, and unequal lengths of follow-up.
However, as pretreatment PSA levels increase, rates of
bNED control decrease across institutions using conventional doses of RT. Figure 3 shows the clinical and
bNED rates for conventional and 3DCRT patients
treated at Fox Chase. A bNED failure was defined as
two consecutive rises in the posttreatment PSA which
exceeded 1.5 ng/ml. These plots (Fig. 3) compare
bNED control for all patients treated with conventional treatment (median dose 69 Gy), for all patients
TABLE I. Twelve-Month PSA Response by Treatment
Technique and Field Size*
Treatment
Prostate only
3DCRT
Conventional
Significance
Pelvis and prostate boost
3DCRT
Conventional
Significance
PSA 艋4.0 ng/ml
PSA 艋1.5 ng/ml
95/99 (96%)
28/33 (85%)
P < 0.03
85/99 (76%)
18/33 (55%)
P < 0.02
58/71 (82%)
35/57 (61%)
P < 0.01
40/71 (56%)
22/57 (38%)
P < 0.05
*Modified with permission from Corn et al. [11].
treated with 3DCRT at doses <71 Gy (median dose 70
Gy), and for all patients treated with 3DCRT with
doses >71 Gy (median dose 74 Gy). There was a significant improvement in bNED control for patients
treated with 3DCRT compared to conventional techniques, and further improvement with higher doses of
3DCRT [23].
Morbidity of Conventional and 3-D Conformal
Radiation Therapy
Early data of 1,020 patients treated with conventional techniques and doses of radiation combined
from the Radiation Therapy Oncology Group (RTOG)
studies 75-06 and 77-06 showed a 3.3% incidence of
grade 3 or higher late GI complications. Fewer than
198
Horwitz et al.
TABLE II. Rates of bNED Control Stratified by Pretreatment PSA for
Conventional RT Series*
PSA
(ng/ml)
<4
4–10
<10
<13
>13
10–20
>20
20–25
>50
EVMS
[45]
Mayo Clinic
[46]
68%
57%
MDACC
[51]
MGH
[47]
84%
66%
82%
44%
Stanford
[48]
WBH
[40]
90%
54%
65%
92%
58%
56%
20%
49%
11%
30%
72%
8%
0%
28%
17%
27%
14%
*EVMS, Eastern Virginia Medical School; MDACC, M.D. Anderson Cancer Center;
MGH, Massachusetts General Hospital; WBH, William Beaumont Hospital.
Fig. 3. Clinical and biochemical
freedom-from-disease rate for conventional and 3DCRT patients.
1% of patients experienced obstruction or perforation
which required surgery to correct. Seventy-nine patients (7.7%) experienced grade 3 or higher late GU
complications, and only 0.5% experienced toxicity
which required major surgery to correct. Only the total dose of >70 Gy significantly predicted late GU complications. No factor significantly predicted late GI
complications [24]. Data from the early National Patterns of Care Study on 1,293 patients showed a 92%
5-year actuarial rate free of complications. Sixty-eight
patients experienced serious complications defined as
those requiring hospitalization. One third of serious
complications required surgical repair. Variables associated with a significant difference in major complica-
tions also included dose >70 Gy. Patients treated with
a two-field technique showed a trend towards increased complications compared to patients treated
with four fields [25–27].
The acute morbidity of 3DCRT was assessed by the
number of patients requiring medication for GI or GU
symptoms during the course of radiation treatment
[28,29]. Table III shows grade 2 and higher rates of GU
and GI morbidity for patients stratified by treatment
technique and field size. Statistically significant differences were observed in morbidity rates between treatment techniques. The greatest difference was noted for
GI morbidity rates for patients treated with small-field
3DCRT (P < 0.001).
External Beam Irradiation of Prostate Cancer
TABLE III. Acute Morbidity (⭓Grade 2) Based on
Treatment Technique and Field Size*
GU
All patients
Small field
Large field
GI
All patients
Small field
Large field
GU/GI
All patients
Small field
Large field
3DCRT
Conventional
Significance
189/668 (28%)
64/233 (27%)
125/435 (29%)
35/93 (38%)
20/49 (41%)
15/44 (34%)
0.044
0.048
0.28
163/668 (24%)
81/233 (35%)
82/435 (19%)
42/93 (45%)
28/49 (57%)
14/44 (32%)
<0.001
<0.001
0.037
299/668 (45%)
120/233 (52%)
179/435 (41%)
63/93 (68%)
38/49 (78%)
25/44 (57%)
<0.001
<0.001
0.033
*3DCRT, three-dimensional conformal radiation therapy; Small
field, prostate only; Large field, pelvis and prostate boost.
The late GI and GU complications following treatment with conventional or 3-D conformal external
beam RT were recently reported. Seven hundred
twelve patients treated between 1986–1994 with conventional (150 patients) or conformal (562 patients)
techniques were analyzed for factors using a modified
RTOG/SWOG scoring system which predicted late GI
(rectal bleeding requiring 艌3 procedures to correct or
proctitis) and GU (cystitis or stricture) morbidity. One
hundred fifteen patients experienced grade 2 or higher
GI toxicity a mean 13.7 months after treatment. Fifteen
of these patients experienced grade 3 or 4 toxicity.
Forty-three cases of grade 2 or higher late GU toxicity
were observed a mean of 22.7 months after treatment.
Only a central axis dose (>74 Gy isocenter) significantly predicted late grade 3 GI toxicity on multivariate analysis. Central axis dose, use of increased rectal
shielding, androgen deprivation therapy before RT,
history of obstructive symptoms, and acute GU symptoms significantly predicted for late grade 2 GU toxicity on multivariate analysis. After the presence of
minor rectal bleeding was noted in 1993, techniques
were developed to reduce the radiation dose to the
anterior rectal wall. The necessity of multiple coagulations was reduced from 5% to 2% at 75–76 Gy [30].
Data from other institutions which treat patients
with 3DCRT show similar reductions in morbidity at
high doses of radiation compared with patients
treated using conventional techniques. Sandler et al.
[31] reviewed the University of Michigan experience
and analyzed 712 patients treated with 3DCRT for late
GI effects. Using the RTOG grading system, only 14
grade 3 or 4 complications were observed. Only increasing dose was significantly predictive of late GI
effects on univariate and multivariate analysis (includ-
199
ing treatment technique, boost technique, age, and T
stage) [31]. Early data from a phase 1 dose escalation
study of 432 patients with clinically localized prostate
cancer from the Memorial Sloan-Kettering Cancer
Center showed 15% grade 2 acute GI toxicity. No
grade 3 or 4 toxicities were noted. Forty percent of
patients experienced acute grade 2 GU toxicity. The
risk of late grade 2 GI or GU complications was 11%
and 5%, respectively, for patients who received 75.6–
81 Gy. Three patients experienced grade 3 or 4 late GI
or GU complications. The 2-year actuarial rate of impotency was 29% among those patients who were
sexually active prior to treatment, and no dose response was observed [32].
Dose Escalation With 3DCRT
Between March 1989–October 1992, we conducted a
dose escalation study in 232 consecutive patients
treated with 3DCRT. Dose was increased from 66 to 79
Gy, and all patients were monitored continuously. The
median follow-up now exceeds 60 months, and 5-year
actuarial bNED control rates are now available [33].
We observed a significant dose response effect for patients with pretreatment PSA levels greater than 10
ng/ml. Figure 4 illustrates the biochemical failure observed with high-dose (艌71 Gy) and low-dose (<71
Gy) radiation for patients with pretreatment PSA levels between 10–19.9 ng/ml. At 5 years, there was almost a 30% difference in bNED control for these T1
and T2 patients. These curves continue to separate as
longer follow-up is obtained. This difference in bNED
control has emphasized the need for higher dose levels in these patients. Figure 5 illustrates the same effect
for patients with pretreatment PSA levels of 20 ng/ml
and greater. A significant difference in 5-year bNED
control rates was noted between patients treated with
high-dose (36%) and low-dose (17%). Five-year rates
of grade 2 and 3/4 GI toxicity were 33% and 8%, respectively, at doses of 75–76 Gy. When anterior rectal
wall shielding was used to keep the dose at <72 Gy to
this structure, the 5-year rates of grade 2 and 3/4 GI
toxicity were reduced to 11% and 2%, respectively.
Results from other institutions using 3DCRT demonstrate similar bNED results when patients are stratified by pretreatment PSA [12,34,35]. At the University
of Michigan, the 5-year actuarial rates of bNED were
88%, 72%, 43%, and 30%, respectively, for patients
with pretreatment PSA values <4, 4–10, 10–20, and >20
ng/ml. Pretreatment PSA, T stage, Gleason score, total
dose, pelvic field treated, surgical status, and favorable grouping were all statistically significant on univariate analysis. However, only pretreatment PSA, T
200
Horwitz et al.
Fig. 4. bNED control for patients
with pretreatment PSA levels of 10–
19.9 ng/ml, treated with low- and
high-dose 3DCRT.
Fig. 5. bNED control for patients
with pretreatment PSA levels >20 ng/
ml, treated with low- and high-dose
3DCRT.
stage, and Gleason score remained independent predictors on multivariate analysis [12]. Roach et al. [34]
reported the UCSF experience of treating 50 patients
with high-grade (Gleason score 8–10) prostate cancer
using 3DCRT. Patients treated with >71 Gy had 4-year
rates of bNED control of 83% vs. 0% for those patients
treated with conventional doses of radiation (<71 Gy)
[34].
bNED Outcome for External Beam and
Retropubic Prostatectomy Patients
Table IV compares bNED results in selected external beam RT series with selected retropubic prostatectomy (RP) series at 5 years [4,5,12,34,36,37]. When patients were stratified by pretreatment PSA, no significant difference in outcome was noted at 5 years
External Beam Irradiation of Prostate Cancer
TABLE IV. Rates of bNED Control Stratified by
Pretreatment PSA for Selected Surgical and
Radiation Series*
Surgery
PSA
(ng/ml)
<4
4–10
<10
<7.5
>7.5
<15
>15
10–20
艋20
>20
UP
[36]
BUMC
[37]
3DCRT
JHU
[4]
FCCC
[5]
92%
83%
80%
UM
[12]
UCSF/UCD
[34]
88%
72%
85%
74%
49%
55%
25%
56%
56%
66%
43%
83%
(>71 Gy)
20%
45%
33%
30%
*3DCRT, three-dimensional conformal radiation therapy. UP,
University of Pennsylvania: 347 patients, median follow-up 18
months, 2-years actuarial rate. bNED failure defined as detectable PSA (>0.2 ng/ml) >4 weeks postoperatively. BUMC, Boston University Medical College: 62 patients, median follow-up
18 months, 4-year actuarial rate. bNED failure defined as detectable PSA (>0.2 ng/ml) >4 weeks postoperatively. JHU, Johns
Hopkins University: 1,354 patients, median follow-up 60
months, 8-year actuarial rate. bNED failure defined as detectable PSA (>0.2 ng/ml) postoperatively. FCCC, Fox Chase Cancer Center: 456 patients, median follow-up 40 months, 5-year
actuarial rate. bNED failure defined as clinical evidence of disease or a serum prostate-specific antigen (PSA) 艌1.5 ng/ml and
rising on two consecutive occasions. UM, University of Michigan: 707 patients, median follow-up 36 months, 5-year actuarial
rate. bNED failure defined as two consecutive PSA rises >2
ng/ml if nadir PSA 艋2 ng/ml, or two consecutive PSA rises if
nadir PSA 艌2 ng/ml, or initiation of hormonal therapy after RT.
UCSF/UCD, University of California, San Francisco/Univeristy
of California, Davis: 50 patients, median follow-up 24 months,
4-year actuarial rate. bNED failure defined as a PSA rise >0.5
ng/ml/year, rise of PSA >1.0 ng/ml, or a positive biopsy.
comparing the treatment in surgical series with selected patients and radiation series with unselected
patients. Two groups recently reported treatment outcome within institutions comparing similarly grouped
patients treated with conventional doses of external
beam RT or RP. Keyser et al. [38] reported the Cleveland Clinic experience of treating 607 patients (RP,
354; RT, 253). The 5-year bNED control rate was 76%
and 75% for RP and RT patients, respectively (P =
0.09). On multivariate analysis, only pretreatment PSA
and Gleason score were significant predictors of
bNED control. Other factors, including treatment
type, were not statistically significant [38]. Similar conclusions were reached by D’Amico et al. [39]. Patients
treated with conventional doses of RT at the Joint Center for Radiation Therapy were compared with pa-
201
tients treated with RP at the University of Pennsylvania. As with the Cleveland Clinic series, pretreatment
PSA, Gleason score, and clinical T stage were independent predictors of bNED control. No statistically significant difference was noted in 2-year bNED control
rates for low-risk (98% vs. 92%, P = 0.45), intermediate-risk (77% vs. 81%, P = 0.86), and high-risk (51% vs.
53%, P = 0.48) patients treated with RP or RT, respectively [39].
Comparisons between treatment modalities are difficult due to significant differences in how patients
were grouped by pretreatment serum PSA levels, the
unequal distribution of prognostic factors from series
to series (e.g., Gleason score, clinical vs. pathological
stage, age), the variability of how bNED control was
defined, the substantial differences in length of followup, and the variety of study designs. In both the surgery and radiation series, the definition of bNED control varied. This was especially true in the radiation
literature. As has recently been shown, depending
upon which definition of bNED control is used (based
upon definitions from several academic radiation oncology departments), statistically significant differences in treatment outcome are obtained attributable
only to the definition chosen [40].
In an effort to develop a unified definition of PSA
cure for reporting successes or failures following irradiation, the American Society for Therapeutic Radiology and Oncology (ASTRO) recently convened a
panel of prostate cancer experts to establish a standard
definition of biochemical cure after RT. The consensus
definition defines biochemical failure as three consecutive increases in posttreatment PSA after achieving a nadir. Biochemical failure is defined as the time
midway between the nadir and first increase in PSA
[41]. It should also be noted that the statistical methodology used to estimate probability of bNED control
should take into account competing risks. Specifically,
cumulative incidence methods should be employed to
account for differing age distributions (i.e., different
percentages in death due to causes other than prostate
cancer). The Kaplan-Meier method does not adjust for
competing risks, and the bias increases with the percent of failures due to competing risks.
Treatment Results in Selected Groups of Patients
Treated With Radiation
Results in younger men. Table V lists the 5-year outcomes for T1 and T2 patients with pretreatment PSA
less than 10 ng/ml who were age 65 years or younger
at time of treatment. This illustrates an extremely favorable outcome for this group with low morbidity, a
low rate of incontinence, and a high rate of 5-year
bNED control. Figure 6 illustrates the durability of
202
Horwitz et al.
TABLE V. Five-Year Outcomes in Patients Age <65
Years With Pretreatment PSA Levels <10 ng/ml, T1–2,
and Gleason Score < 7
Parameter
Five-year rate
Actuarial bNED control
RTOG GI grade 3/4
RTOG GU grade 3/4
Potency preservationa
87%
<1%
<1%
73%
a
Percentage of mean potent pretreatment able to have sexual
intercouse posttreatment.
bNED control for this group of patients with available
pretreatment PSAs and more than 5 years of follow-up
[42]. Similar results in outcome were reported by Poen
et al. [43] for 396 patients treated at Stanford University. No statistically significant differences in causespecific survival and distant metastases-free survival
were observed between patients age 60 years and less
and those older. Patients age 60 years and less had
statistically significant improvements in median survival, local control, and disease-free survival [43].
Results in patients with stage T1c cancer. The 5-year
bNED control for 176 patients with clinical stage T1c
cancer who had pretreatment PSA levels <20 ng/ml
treated with 3DCRT was 85% (Fig. 7). The 5-year rate
of bNED control compared favorably to surgical patients with similar pretreatment prognostic variables,
and results were durable for the complete length of
follow-up [44].
Results in patients with stage T2a cancer. The bNED
control rate for 76 patients with clinical stage T2a cancer who had pretreatment PSA levels <10 ng/ml
treated with 3DCRT was 77% at 8 years (Fig. 8). As
with the T1c patients, the bNED control rate was excellent and the results were durable during the entire
period of observation. For comparison with prostatectomy results, data from Johns Hopkins University for
clinical stage T2a demonstrate 85% bNED control at 5
years and 68% bNED control at 8 years [4]. Although
difficult to compare directly, these results appear
equivalent based upon similar pretreatment PSA and
T stage.
DISCUSSION
External beam irradiation remains a mainstay in the
treatment of patients with prostate cancer. Current results of treatment with conventional doses of radiation
(<70 Gy) show similar rates of bNED control when
patients are stratified by pretreatment PSA levels
[35,40,45–48]. However, as pretreatment PSA levels increase, rates of bNED control decrease. The implementation of new technologies, including patient immobi-
lization devices, CT treatment planning, beam eye
view visualization and planning, dose calculation in
3-D, multileaf collimation, and electronic portal imaging, has improved the radiotherapeutic management
of prostate cancer, resulting in increased radiation
dose to the prostate. Simultaneously, these techniques
have allowed the reduction in volume of normal tissue
which receives clinically significant doses of radiation,
resulting in the reduction in complication rates [29].
In addition to the utilization of these new technologies, better understanding of tumor biology and prognostic factors, including pretreatment PSA level, Gleason score, and clinical T stage, is allowing better patient selection. Multiple studies in both the radiation
and surgical literature have demonstrated that the
pretreatment PSA level is the single most important
independent prognostic variable to predict and assess
treatment efficacy [4,36,40,49–51].
Results of treatment with 3DCRT with long-term
(>5 years) PSA follow-up are becoming available
which demonstrate superior bNED control rates using
this new technique. Data from several institutions
demonstrate that when the volume of normal tissue is
reduced, the total dose to the prostate can be safely
increased, resulting in improved bNED control. Data
from our institution demonstrate that this is particularly pronounced for patients with intermediate levels
of pretreatment PSA [13].
Extensive long-term data on the GI and GU morbidity of external beam RT using conventional doses
of radiation have been available for more than a decade. Data from several large national studies have
shown consistently that the dose of radiation (>70 Gy)
and the technique used contribute significantly to normal tissue complication rates [24,25]. Now data are
becoming available from several institutions treating
patients with 3DCRT that GI and GU morbidity is not
significantly worsened despite the increased doses of
radiation used [30,31].
Because higher doses of radiation can be delivered
to the prostate (without substantially higher rates of
normal tissue complications) using 3DCRT, evidence
demonstrates that bNED control rates are significantly
improved. Five to seven-year actuarial data from several institutions, including Fox Chase and the University of Michigan, show increased rates of bNED control, especially for patients with pretreatment PSA levels >10 ng/ml (a group that does not have durable
bNED control rates with conventional RT). For patients with pretreatment PSA levels between 10—20
ng/ml, the advantage of 3DCRT was evident, with an
almost 30% difference in bNED control at 5 years
[5,12]. A major task for the radiation oncology community in the future is to expand the use of 3DCRT
External Beam Irradiation of Prostate Cancer
203
Fig. 6. bNED control for T1/T2 patients <65 years old, with pretreatment PSA <10 ng/ml.
Fig. 7. bNED control for clinical
T1c patients treated with 3DCRT.
technology beyond the limited numbers of expert facilities currently utilizing this treatment program.
CONCLUSIONS
Prostate cancer patients need to be well-informed of
the results and morbidities of the various treatment
options available so that they can make an informed
decision regarding treatment modality. Using known
prognostic factors including pretreatment PSA, Gleason score, and T stage to categorize patients into similar prognostic groups, patients with clinically localized prostate cancer can effectively be treated with
high-dose 3-D conformal radiation therapy with mini-
204
Horwitz et al.
Fig. 8. bNED control for clinical
T2a patients treated with 3DCRT.
mal long-term GI and GU toxicity. The results presented in this communication of conventional and 3-D
conformal radiation therapy provide some basis for
patient and physician choice.
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