Combining
hormone therapy (anti-androgen) with radiation
This topic is still controversial but
the studies now suggest the following based on whether the cancer is low risk,
intermediate risk or high risk as defined below: (the key studies RTOG 85-31, 86-10,
92-02, 94-13 and EORTC are described: here
for the details, note that EORTC
trial showed improved overall survival) and the recent Harvard study showed a
survival benefit from short term (6 months) hormone therapy in the intermediate risk group
(see study and
editorial.)
Six months is preferable to only 3 to 4 months for Gleason of 7 (go
here). Overall the most obvious benefits occur in patients with higher Gleason
score or PSA (go
here.)
If the risk of relapse are too high then 6 months of hormones may not be
enough (go here). In
the current RTOG trial (0815) for patients with
intermediate risk they are randomizing high does radiation alone (79.2Gy or
1.8Gy X 44) or combined with 6 months of combined hormone therapy (XRT
starts 8 weeks after starting hormones). The TROG 96-01 trial for
intermediate risk prostate cancer showed long term survival benefits from 6
months of hormone therapy (go here).
Another study showed that for patients with high risk prostate cancer
hormones alone is not adequate and hormones should be combined with
radiation (go here). The
NCCN radiation guidelines include no hormones in low risk, 4-6 months in
intermediate risk and 2-3 years for high risk men. Also read the
main hormone section for a discussion of side
effects of hormones.
According to the
NCCN guidelines (go
here) it is not necessary to combine radiation with hormone therapy (Lupron or Zoladex) for low risk
patients (Gleason 6 and PSA less than 10) but may be considered for 4 to 6 months in the intermediate risk
patients (Gleason 7 or PSA between 10 and 20) and definitely be used for 2 to 3 years in the high risk patients
(Gleason 8 - 10 or PSA over 20). There is still uncertainty about how long
the hormone therapy must continue (see
here). Hormonal therapy combined with seeds is discussed in the seed section. A recent review showed improved overall survival in patients with locally advanced prostate cancer (go here) particularly with long term hormone use. |
1. if the tumor is small and early
stage (T1c or small T2a) and the PSA is less than 10 and the Gleason is 6 or lower, then
radiation alone is probably adequate based on survival (but even in this group hormone
therapy probably improves the cure rate or delays a relapse with a rising PSA) 2. if the cancer has any one risk factor (stage T2b or PSA over 10 or Gleason of 7) then the patient should get neoadjuvant hormonal therapy (which means a Lupron shot two months before radiation and then hormones continued during the radiation period for a total of 4 - 6 months, it's unclear if a longer course of hormone therapy would be even better.) The RTOG 94-08 showed a survival benefit in this group (but not low risk) for 4 months of combined hormonal therapy (go here). 3. if the cancer had more than two risk factors, or the PSA > 20 or Gleason 8 or higher, the the hormones should probably be continued for an indefinite period ( 2 to 5 years, see the NCCN guidelines) and here. |
The duration of hormone therapy is uncertain, short term (4 - 6 months) definitely delays recurrences but may increase survival only in the intermediate risk group. (in RTOG 86-10 the 4 mos hormones increased overall survival from 52%/5y to 72%/5y only in the Gleason 2-6 group.) but high risk patients may need long term hormones to show a survival benefit (in RTOG 92-02 comparing 28 months with 4 months of hormones, only the Gleason 8-10 had improved overall survival (80% versus 69%.) |
The Cleveland Clinic (Davies-Johns, ASTRO 2000) showed the benefits of 6 months of hormones by risk group: low (PSA< 10, GS <7), intermediate (PSA 10-20 or GS 7) or high risk (T3 or GS> 7 or PSA>20) as noted: |
Risk Group | No Hormones | 6 months Hormones |
Low | 81%/5y | 94%/5y |
Intermediate | 56%/5y | 98%/5y |
High Risk | 30%/5y | 85%/5y |
A Harvard study (D'Amico ASTRO 2000) of 6 months of hormones and external beam irradiation came to the same conclusion by risk group low(GS 6 and PSA < 10), intermediate (T2b or GS7 or PSA 10-20) or High (T2c, GS>7 or PSA>10) as below: |
Risk Group | no Hormones | 6 Months Hormones |
Low | 84% | 92% |
Intermediate | 62% | 86% |
High | 43% | 67% |