Long-Term Treatment Sequelae After External Beam Irradiation With or Without Hormonal Manipulation for Adenocarcinoma of the Prostate: Analysis of Radiation Therapy Oncology Group Studies 85-31, 86-10, and 92-02

Abstract

Purpose-Late gastrointestinal and genitourinary morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians, and patients alike. Additionally for high risk/locally advanced patients the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large RTOG studies 85-31, 86-10, and 92-02 to try to address the aforementioned issues.Methods-2,922 patients were accrued with a median follow up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short course hormone therapy (STH) vs. RT + long term hormone therapy (LTH).Results-Multivariate analysis reveals that age > 70 was statistically significantly associated with a decrease in late any grade 3+ toxicity (HR= 0.78, p=0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of grade 3+ GI, GU, and other toxicity compared to RT alone (p = .00006; p=0.0037; p=0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of grade 3+ GU toxicity compared to RT alone (p=0.023).Conclusion-These data show that external beam radiation therapy remains a safe option for locally advanced/high risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment.

Therapeutic outcomes of neoadjuvant and concurrent androgen‐deprivation therapy and intensity‐modulated radiation therapy with gold marker implantation for intermediate‐risk and high‐risk prostate cancer

“…26 The use of ADT in combination with radiotherapy has been reported to reduce radiotherapy-associated GU and GI toxicity. 28 All patients in the present study underwent ADT, and their therapeutic outcomes were equivalent to or better than that those achieved by administering high-dose (!80 Gy) radiotherapy, which suggests that the combined use of ADT and IMRT might contribute to improved therapeutic outcomes in prostate cancer. Furthermore, our patients showed few serious adverse effects.…”

Comparison of dosimetric parameters and acute toxicity after whole-pelvicvsprostate-only volumetric-modulated arc therapy with daily image guidance for prostate cancer

“…Whether androgen suppression is correlated with increased toxicity is a controversial issue in the literature. 35,36 However, we cannot exclude the possibility that prostate volume reduction after ADT likely yielded the low incidence of acute bladder and rectal toxicity in the WP group. Second, there was a short follow-up period.…”

Intensity Modulated Radiation Therapy Reduces Gastrointestinal Morbidity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

“…A recently published update of the same study demonstrated statistically significant differences in toxicity between the four arms with the neoadjuvant hormone therapy and whole pelvis RT group having the highest rate of late GI toxicity (11). On the other had, a pooled analysis of the RTOG studies 85-31, 86-10 and 92-02 suggested a protective role for AD in terms of GI and GU toxicity (10). It unclear as to whether these conflicting results is related to categorization of toxicity.…”

“…Some studies have suggested that the addition of AD increases the risk of GI and GU toxicity while others have not (7,(9)(10)(11). At Fox Chase Cancer Center, our experience is that the addition of long-term AD (LTAD) significantly increases grade 2 and higher GI and GU toxicity with in patients treated with 3DCRT for locally advanced prostate cancer (9).…”