The role of proton beam therapy (PBT) as monotherapy for localized prostate cancer (PCa) remains unclear. The purpose of this study was to evaluate the efficacy and adverse events of PBT alone for these patients. Between January 2011 and July 2014, 218 patients with intermediate- and high-risk PCa who declined androgen deprivation therapy (ADT) were enrolled to the study and were treated with PBT following one of the following protocols: 74 Gray (GyE) with 37 fractions (fr) (74 GyE/37 fr), 78 GyE/39 fr, and 70 GyE/28 fr. The 5-year progression-free survival rate in the intermediate- and high-risk groups was 97% and 83%, respectively (p = 0.002). The rate of grade 2 or higher late gastrointestinal toxicity was 3.9%, and a significant increased incidence was noted in those who received the 78 GyE/39 fr protocol (p < 0.05). Grade 2 or higher acute and late genitourinary toxicities were observed in 23.5% and 3.4% of patients, respectively. Our results indicated that PBT monotherapy can be a beneficial treatment for localized PCa. Furthermore, it can preserve the quality of life of these patients. We believe that this study provides crucial hypotheses for further study and for establishing new treatment strategies.

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Objective Many treatment options have guaranteed long-term survival in patients with localized prostate cancer and health-related quality of life has become a greater concern for those patients. The purpose of this study was to reveal the health-related quality of life after proton beam therapy and to clarify the differences from other treatment modalities for prostate cancer. Methods Between January 2011 and April 2016, 583 patients were enrolled in the study and health-related quality of life outcomes using the Expanded Prostate Cancer Index Composite questionnaire were evaluated and compared with previous research targeted at Japanese patients. Results We found a significant decrease in the least square mean scores for urinary and bowel domains excluding the incontinence subscale after proton beam therapy (P &lt; 0.0001) and recovery at a year following treatment. The scores for sexual function in patients without androgen deprivation therapy decreased each year after proton beam therapy (P &lt; 0.0001). The scores for hormones in patients without androgen deprivation therapy remained high and those of patients with androgen deprivation therapy were lower before treatment but were comparable to those of non-androgen deprivation therapy patients at 2 years post-treatment. We found that the impact of radiotherapy including proton beam therapy on urinary condition and sexual function was lower than that of surgery. Conclusions For the first time in Japan, we investigated health-related quality of life using Expanded Prostate Cancer Index Composite questionnaires in patients with prostate cancer after proton beam therapy and compared it with other treatment modalities.

: The lysosomal protease cathepsin D is associated with tumor progression in malignant tumors, but its presence in pre-malignant dysplastic cells has not been established. The purpose of this study is to evaluate the expression patterns of the cathepsin D, Ki-67, and p53 proteins in dysplastic cells in uterine cervical intraepithelial neoplasias (CINs). In 52 patients with uterine CINs, expression of the cathepsin D, Ki-67, and p53 proteins was assessed in dysplastic cells by immunohistochemistry with monoclonal antibodies against cathepsin D, Ki-67, and p53. Immunohistochemical analysis revealed high levels of cathepsin D (>10% cathepsin D-positive dysplastic cells) in 3 of 17 cervical intraepithelial neoplasia (CIN) 1 specimens, 16 of 20 CIN2 specimens, and in all 15 CIN3 specimens. Cathepsin D expression was significantly higher in CIN2 and CIN3 specimens than in CIN1 specimens (P < 0.01). but did not differ significantly between CIN2 and CIN3 specimens. The proportion of dysplastic cells that expressed nuclear Ki-67 was 26.41% in CIN1 specimens, 50.35% in CIN2 specimens, and 76.33% in CIN3 specimens. Ki-67-positive dysplastic cells were significantly increased in CIN2 and CIN3 specimens as compared to CIN1 specimens (P < 0.01), and in CIN3 specimens as compared to CIN2 specimens (P < 0.01). High expression of nuclear p53 (>10% p53-positive dysplastic cells) was detected in 4 of 17 CIN1 specimens, 12 of 20 CIN2 specimens, and in 11 of 15 CIN3 specimens. Nuclear p53 expression was significantly higher in CIN2 and CIN3 specimens than in CIN1 specimens (P < 0.01), but did not differ significantly between CIN2 and CIN3 specimens. Compared to dysplastic cells in CIN1, dysplastic cells in CIN2 have an increased invasive growth potential, as shown by their increased expression of cathepsin D, a higher proliferating potential as shown by their increased expression of Ki-67, and a higher p53 expression.

97 Background: Although there are many patterns of treatment in localized prostate caner, proton beam therapy has no definite role in them. We aimed to assess the outcomes of proton beam therapy (PBT) alone for patients with intermediate- and high-risk prostate cancer, and to clarify the role of PBT in the treatments. Methods: Between Jan. 2011 and Sep. 2014, 204 patients with intermediate- and high-risk prostate cancer who declined to receive hormonal treatments until biochemical or clinical recurrence were enrolled in the study. All patients were irradiated a 70-78 GyE in 28-39 fractions, and pre-treatment risk groups were classified in accordance with the D’Amico criteria. The 5-year (biochemical or clinical) recurrence-free survival (RFS), late gastrointestinal (GI) and genitourinary (GU) toxicity (NCI-CTCAE ver.4.0) were evaluated. We conducted a survey on sexual quality of life (QOL) every six months to evaluate any long-term damage to the sexual function using the Expanded Prostate Cancer Index Composite (EPIC). Results: The mean age and the follow-up period were 66 (range: 39-86) and 52 months (range: 24-76 months), respectively. The 5-year RFS rates in intermediate- (n = 112) and high- (n = 92) risk groups were 96.9% and 83.4%, respectively. There was a significant difference between the two groups (p = 0.002). The incidence of grade 2+ GI and GU toxicity were 4% and 3%, respectively. We found a significant difference in the GI toxicity between the two radiation protocols of 78GyE/39fractions (n = 6, 11%) and 70GyE/28fractions (n = 0, 0%) (p < 0.01). A 5.8% decrease in average after adjusting for aging was found in sexual summary score in six years after treatment, which was equivalent to aging of three years. Conclusions: Proton beam therapy alone demonstrated favorable results in patients with intermediate- and high-risk prostate cancer. Although more patients and longer follow-up are necessary to confirm the outcomes, these results suggested a hypothesis that proton beam therapy might not require androgen deprivation therapy in the treatment of localized prostate cancer, which could lead to a possibility of preserving of sexual function. Clinical trial information: MPTRC-N2 and N3.