Alaska’s Stampede Trail could be more aggressive

James Fleck & Fernando Souza: Anticancerweb, Dec 29^th, 2018

Data from the International Agency for Research on Cancer (IARC) show prostate carcinoma as the most prevalent malignant tumor in man. The epidemiological leadership position is based on its high global incidence (ASR = 29.3) associated with an indolent biological behavior, which has been reflected in a quite lower mortality rate (ASR = 7.6). Around three-quarter of the cases are diagnosed over 65 years-old. Despite the indolent behavior and awareness campaigns on early detection, some types of prostate cancer already express lymph node involvement (12%) or metastatic disease (5%) at the time of diagnosis. This late detection leads to a worsening in prognosis, with a median 5-years survival rate of only 30%.

Until recently, the treatment of metastatic or locally-advanced prostate cancer was exclusively systemic, consisting primarily of androgenic deprivation therapy associated with docetaxel. Radiation therapy was reserved for eventual palliation of symptoms. However, previous experimental models have supported a rational for the use of primary tumor irradiation even on prostate cancer advanced stages.

In an attempt to achieve a better overall survival for metastatic prostate cancer, the elegant multicenter British Stampede Trial designed the study arm H. A total of 2061 patients diagnosed with metastatic prostate carcinoma were randomly assigned to exclusive systemic therapy (control group) or systemic therapy + primary tumor directed radiation therapy (PT-RT). Two radiotherapy schedules were used: Weekly fractions of 6 Gy / 6 weeks (36 Gy) or 20 daily fractions of 2.75 Gy /4 weeks (55 Gy). Unfortunately, the alternative hypothesis, using PT-RT did not change the overall survival rate in the entire group of patients with metastatic or locally-advanced prostate cancer (HR = 0.92 p = 0.266). However, in exploratory analysis, it was possible to identify a subgroup of patients (40 % of the original sample) with low-metastatic burden (< 4 bone metastases restricted to axial skeleton and/or lymph node involvement) where an overall survival benefit was achieved with the additional use of PT-RT (HR 0.68 p = 0.007). The benefit was observed in both PT-RT schedules. The low incidence of acute and late toxicity stablished a new standard of treatment for low-metastatic burden prostate carcinoma. However, it is still unknown the recommended dose of PT-RT, since both tested schedules were below the minimum required curative dose intensity (60 Gy in 20 fractions / 4 weeks). In Stampede Trial, the decision to use a lower PT-RT dose intensity was arbitrary and sustained by nonmaleficence principle.

Stampede Trial runs in the opposite direction of the Stampede Trail, a small route located near Denali National Park in Alaska, immortalized in the movie named “Into the Wild”. The Stampede Trail’s wilderness was responsible for the tragic outcome reported in Jon Krakauer’s article entitled “Death of an Innocent”. In the summer of 1992, the young American adventurer Christopher McCandless attempted to survive inside the bus 142. Unfortunately, he died of starvation after four months of isolation. Ironically, Christopher Parker reported in Lancet 2018 the Stampede Trial – Arm H results, showing 81% of three-year survival in patients with low-metastatic burden prostate carcinoma, handled with androgenic deprivation therapy + PT-RT.

ASR = Age Standardized Rate

Reference:

Christopher C Parker, Nicholas D James, Christopher D Brawley, et al: Radiotherapy to the primary tumor for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomized controlled phase 3 trial, Lancet Oct 21^st, 2018

YouTube: MrMysteria - Magic Bus Stampede Trail 6.5.2016