Replacing LNT: The Integrated LNT-Hormesis Model.

Many scientists and regulators utilize the linear no-threshold (LNT) relationship to estimate the likelihood of carcinogenesis. The LNT model is incorrect and was adopted based upon false pretenses. The use of the model has been corrupted by many to claim that even the smallest ionizing radiation dose may initiate carcinogenesis. This claim has resulted in societal harm.

Long-term outcomes for patients with prostate cancer having intermediate and high-risk disease, treated with combination external beam irradiation and brachytherapy.

Background. Perception remains that brachytherapy-based regimens are inappropriate for patients having increased risk of extracapsular extension (ECE). Methods. 321 consecutive intermediate and high-risk disease patients were treated between 1/92 and 2/97 by one author (M. Dattoli) and stratified by NCCN guidelines. 157 had intermediate-risk; 164 had high-risk disease. All were treated using the combination EBRT/brachytherapy ± hormones. Biochemical failure was defined using PSA >0.2 and nadir +2 at last followup. Nonfailing patients followup was median 10.5 years. Both biochemical data and original biopsy slides were independently rereviewed at an outside institution. Results. Overall actuarial freedom from biochemical progression at 16 years was 82% (89% intermediate, 74% high-risk) with failure predictors: Gleason score (P = .01) and PSA (P = .03). Hormonal therapy did not affect failure rates (P = .14). Conclusion. This study helps to strengthen the rationale for brachytherapy-based regimens as being both durable and desirable treatment options for such patients. Prospective studies are justified to confirm these positive results.

Prostatic acid phosphatase adversely affects cause-specific survival in patients with intermediate to high-risk prostate cancer treated with brachytherapy.

OBJECTIVES: To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT). METHODS: From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS. RESULTS: The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393). CONCLUSIONS: The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.

Reviving the acid phosphatase test for prostate cancer.

Prostatic acid phosphatase (PAP) emerged as the world's first clinically useful tumor marker in the 1940s and 1950s. With the introduction of the prostate-specific antigen (PSA) test in the 1980s, which performed significantly better than PAP in terms of screening and monitoring response to treatment, PAP fell into disfavor. An increasing number of recent studies have identified PAP as a significant prognostic factor for patients with intermediate- and high-risk prostate cancer. PAP appears to be particularly valuable in predicting distant failure in higher-risk patients for whom high levels of local control are achieved with aggressive initial local treatment. As prostate cancer care becomes increasingly focused on identifying the minority of patients who would benefit from aggressive systemic therapy, a reevaluation of the potential contribution of the prostatic acid phosphatase test seems timely.

Long-term outcomes after treatment with brachytherapy and supplemental conformal radiation for prostate cancer patients having intermediate and high-risk features.

BACKGROUND: This study summarizes long-term outcomes from treatment of prostate cancer with increased risk of extracapsular cancer extension (ECE) using brachytherapy-based treatment. METHODS: A total of 282 consecutive patients were treated from 1992-1996 by 1 author (M.D.). Two hundred forty-three patients had at least 1 higher risk feature for ECE including Gleason Score 7-10 (172), prostate-specific antigen (PSA) above 10 (166), and clinical stages T(2c) (109) and T(3) (107). Using National Comprehensive Cancer Network (NCCN) guidelines, 119 patients had intermediate-risk disease and 124 had high-risk disease. Patients received pelvic 3-dimensional conformal external beam radiation followed by a palladium (Pd)-103 boost. Generous brachytherapy margins were utilized. Biochemical failure was defined using ASTRO Consensus Definition, nadir +2 and PSA >0.2 ng/mL at last follow-up. The nonfailing patient follow-up period was 1-14 years (median, 9.5 years). Biochemical data and original biopsy slides were independently re-reviewed at the University of Washington (by K.W. and L.T., respectively). RESULTS: Overall actuarial freedom from biochemical progression at 14 years was 81%, including 87% and 72% having intermediate and high-risk disease, respectively. Absolute risk of failure decreased progressively, falling to 1% beyond 6 years after treatment. All failing patients had prostate biopsies without evidence of local recurrence. The strongest predictor of failure was Gleason score (P = .03) followed by PSA (P = .041). Treatment morbidity was limited to temporary RTOG grade 1-2 urinary and gastrointestinal symptoms. CONCLUSIONS: High tumor control rates are possible with beam radiation followed by Pd-103 brachytherapy. Despite perceptions that brachytherapy is inappropriate for patients at higher risk for ECE, this series strengthens the rationale that brachytherapy-based treatment may be a desirable modality for such patients.

Long-term prostate cancer control using palladium-103 brachytherapy and external beam radiotherapy in patients with a high likelihood of extracapsular cancer extension.

OBJECTIVES: To report the long-term biochemical control rates with brachytherapy-based treatment for patients with prostate cancer at high risk of extracapsular cancer extension. METHODS: A total of 243 consecutive patients with at least one higher risk factor (Gleason score of 7 or worse, prostate-specific antigen [PSA] level greater than 10 ng/mL, or elevated prostatic acid phosphatase level greater than 2.5 U) who were treated with palladium-103 plus supplemental external beam radiotherapy from 1992 through 1996 were included in this study. Patients received 41 Gy external beam radiotherapy to a limited pelvic field, followed 4 weeks later by a palladium-103 boost. The prescribed minimal palladium-103 dose to the prostate was 80 to 90 Gy. Freedom from biochemical failure was defined as a serum PSA level of 0.2 ng/mL or less at the last follow-up visit. RESULTS: Of the 243 patients, 41 developed biochemical failure. The overall actuarial freedom from biochemical progression rate at 13 years was 81%, with 198 patients followed up for longer than 5 years. The overall actuarial freedom from failure rate for the 93 patients with a PSA level of 10 ng/mL or greater and Gleason score of 7 or greater was 74% at 5 years and 72% at 10 years. The overall actuarial freedom from failure rate for the 66 patients with elevated prostatic acid phosphatase was 65% at 10 years. The absolute risk of failure decreased progressively with time, falling to 1% by 6 years after treatment. On Cox proportional hazard multivariate analysis, considering each factor as a continuous variable, the strongest predictor of failure was the acid phosphatase level (P <0.0001), followed by Gleason score (P = 0.42) and PSA level (P = 0.15). CONCLUSIONS: The evidence from this patient group at high risk of extracapsular cancer extension suggests that the relatively high tumor control rates with brachytherapy-based therapy are durable.

Long-term outcomes after treatment with external beam radiation therapy and palladium 103 for patients with higher risk prostate carcinoma: influence of prostatic acid phosphatase.

BACKGROUND: The objective of this study was to define the long-term prognostic significance of prostatic acid phosphatase (PAP) levels in patients with higher risk, early-stage prostate carcinoma. METHODS: One hundred sixty-one consecutive patients with Stage T1-T3 prostate carcinoma (according to the 1992 criteria of the American Joint Committee on Cancer) were treated from 1992 through 1996. Each patient had a Gleason score > or = 7 and/or a prostate specific antigen (PSA) level > 10 ng/mL. The original biopsy slides for 130 of 161 patients were retrieved and rereviewed by a single pathologist (L.T.). Enzymatic PAP measurements were determined using a standard method. Values up to 2.5 Units were considered normal. Patients received 41 grays (Gy) of external beam radiation therapy to a limited pelvic field followed 4 weeks later by a palladium 103 (Pd-103) boost using transrectal ultrasound and fluoroscopic guidance as described previously. The prescribed minimum Pd-103 dose to the prostate was 80 Gy (pre-National Institute of Standards and Technology [NIST]-99). Freedom from biochemical failure was defined as a serum PSA level < or =0.2 ng/mL at last follow-up. RESULTS: There was little correlation between pretreatment PSA levels, Gleason scores, and PAP measurements. Thirty-eight patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 10 years is 79%, with 118 patients followed for > 5 years. In a multivariate Cox proportional hazards analysis that considered each factor as a continuous variable, the strongest predictor of failure was PAP (P = 0.0001), followed by Gleason score (P = 0.13), and PSA (P = 0.04). PAP was especially helpful in stratifying patients with pretreatment PSA levels between 4 ng/mL and 20 ng/mL, for whom the prognosis does not different when they are subdivided into PSA categories. When the PAP subgroup analysis was limited to this relatively favorable group, there was a wide range of prognoses. CONCLUSIONS: The biochemical cure rate was remarkably high among the 161 patients evaluated. The fact that the PAP was the strongest predictor of long-term biochemical failure in patients with otherwise higher risk features reported here suggests that it may be a more accurate indicator of micrometastatic disease compared with the Gleason score and the PSA level. This report adds to the rationale for reintroducing PAP measurement into general practice.