Lancet: RT + more hormone therapy doubles prostate cancer survival

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Men with locally advanced prostate cancer treated with six months of hormone therapy combined with radiotherapy halve their chances of dying from the disease compared with patients who receive radiation therapy alone, according to the 10-year results of the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial published online March 25 in the Lancet Oncology.

In the 1990s, researchers determined androgen deprivation therapy (ADT), in addition to radiotherapy, could improve radiotherapy survival among patients with locally advanced prostate cancer. However, prolonged ADT is associated with multiple adverse side effects, so clinicians and patients are reluctant to use the treatment long-term.

In an attempt to assess the impact of three-month and six-month neoadjuvant ADT (NADT), the researchers reviewed 10-year data from the TROG 96.01 trial, which compared radiotherapy alone with three-month and six-month NADT.

The trial included 802 men diagnosed with locally advanced prostate cancer between June 1996 and February 2000. Patients were randomized to radiotherapy alone, radiotherapy with three-month NADT or radiotherapy with six-month NADT. The radiation dose for all groups was 66 Gy. Primary endpoints were prostate cancer-specific mortality and all-cause mortality.

Researchers calculated 10-year cumulative incidence for each endpoint and also completed a simulation analysis assuming a 74 Gy radiation dose to estimate the impact of the higher doses more commonly used today.

According to James W. Denham, MD, of the University of Newcastle in Australia, the six-month NADT cohort fared better on all endpoints compared with the three-month NADT cohort and the radiotherapy alone cohort. Deaths from prostate cancer and other causes were 70 and 66 (out of 270), respectively, in the radiotherapy alone group, 56 and 54 (out of 256 ) in the three-month NADT group and 33 and 55 (out of 267) in the six-month NADT group.

“Prostate cancer-specific mortality at 10 years was 22.0 percent for radiotherapy alone, 18.9 percent for three-month NADT and 11.4 percent for six-month NADT,” wrote Denham.  Similarly, the six-month NADT cohort fared best with respect to the 10-year incidence of PSA progression at 52.3 percent, compared with 60.4 percent for three-month NADT and 73.8 percent for radiotherapy alone.

Finally, the simulation analysis indicated that increasing the dose to 74 Gy would have reduced prostate cancer-specific mortality in all groups, offered the authors.

“The TROG 96.01 trial provides evidence that men with non-metastatic, locally advanced cancers can be treated successfully, and have few late side effects, with as little as six months of NADT and radiation…We believe that six months of NADT in combination with contemporary radiation techniques and doses will remain an effective treatment option in the next decade, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation,” concluded Denham and colleagues.

In an accompanying Lancet comment, Chris Parker, from Royal Marsden Hospital in Sutton, England, noted, “The magnitude of benefit for six-month NADT compared with radiotherapy alone is truly remarkable,” while acknowledging the pre-existing lack of clinical consensus for a minimum duration of NADT.

Parker also pointed out that “the benefit of NADT in addition to modern escalated dose radiotherapy is uncertain,” but suggested that the benefits of NADT are greater than those of radiotherapy dose escalation as dose escalation has not yet been shown to affect mortality.

Current trials—specifically EORTC 22991, RTOG 0815 and MRC RT01—are designed to ascertain the benefits of NADT in conjunction with escalated dose radiotherapy.

Parker concluded, “TROG 96.01 confirms that NADT significantly reduces mortality after radiotherapy for high-risk prostate cancer, and is a standard of care…It strongly suggests that men receiving NADT should have at least six months of treatment.”