Clinical Practice Guidelines for the management of locally advanced ...

3.2.2 Adjuvant systemic chemotherapy
See chapter 10 Emerging therapies, p116
3.2.3 Adjuvant androgen deprivation therapy
See section 3.1.3 Radiotherapy and androgen deprivation therapy, p30.
3.3 Node-positive disease
3.3.1 Radiotherapy and adjuvant androgen deprivation therapy
The role of radiotherapy for node-positive disease is controversial. There are three RCTs containing
subgroups of node-positive (primarily biopsy proven) patients that evaluate any effect of adjuvant
androgen deprivation when combined with radiotherapy. Two RCTs examined radiotherapy with
adjuvant ADT versus radiotherapy with ADT as a possible treatment on progression. The first, RTOG
85-31, used LHRH agonist until progression 112 . The second used a non-steroidal anti-androgen for a
minimum of two years. 113 The third RCT examined radiotherapy with concurrent plus adjuvant ADT
(orchidectomy prior to radiotherapy) versus radiotherapy with ADT on progression. 114 The largest
RCT, RTOG 85-31, was of medium quality for survival whereas the two smaller RCTs were of low
quality. In all three trials the analyses for node-positive disease were unplanned subgroup analyses,
increasing the risk that the arms may not be balanced for potential risk factors in this subgroup of
patients. The largest subgroup with 173 participants was from RTOG 85-31. The Granfors study
contained a subgroup of 39 node-positive patients and the Iversen study contained only 14 patients in
their node-positive subgroup. 113 Radiotherapy doses were either not described or varied in all studies.
The RTOG 85-31 and Granfors studies provided data for survival, prostate cancer survival and
disease progression. The RTOG 85-31 study showed a trend towards improved survival with 6.5 years
median follow-up. A multivariate analysis of patients for whom Gleason scores were available and
which took into account Gleason score and whether the men had undergone radical prostatectomy
found a statistically significant improvement with adjuvant ADT, with a nine-year survival rate of
62% for adjuvant ADT versus 38% for radiotherapy alone. The smaller Granfors trial with a median
follow-up of 9.3 years showed a statistically significant survival benefit for immediate orchidectomy
with a nine-year survival rate of 50% for immediate orchidectomy therapy versus 13% for
radiotherapy alone. 114 Similar results were found for prostate cancer mortality. With longer follow-up
to 19 years, this survival benefit was maintained. 115 The Iversen study had reduced rates of clinical or
biochemical progression with anti-androgen therapy in their very small subgroup of men. 113
Isolated biopsy proven node-positive disease represents a relatively small cohort of prostate cancer
patients. In these patients there is potential for a major survival benefit with androgen deprivation in
addition to radiotherapy. However it is not known whether adding radiotherapy to androgen
deprivation for node-positive patients provides any benefit.
Only one of the three RCTs, RTOG 85-31, examined radiotherapy toxicity outcomes for adjuvant
ADT–in this trial LHRH agonist therapy–for the node-positive patient subgroup.
The authors reported that the incidence of grade 3 and 4 acute and late toxicities was not statistically
significantly different.
As long-term adjuvant androgen deprivation as an adjuvant to radiotherapy appears to improve the
survival of men with biopsy node-positive prostate cancer, no evidence of increased radiotherapeutic
toxicities would have a substantial clinical impact. However, the hormone-associated toxicities that
would have an impact on quality of life were not assessed, reducing the clinical impact.
One trial reports no difference in grade 3 and 4 toxicities with LHRH agonist treatment after
radiotherapy. Other known toxicities of hormonal therapy were not reported. 112
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