PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes. PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen = 15 ng/mL were randomly assigned to a total dose of either 70.2 Gray equivalents (GyE; conventional) or 79.2 GyE (high). No patient received androgen suppression therapy with radiation. Local failure (LF), biochemical failure (BF), and overall survival (OS) were outcomes. Results A total of 393 men were randomly assigned, and median follow-up was 8.9 years. Men receiving high-dose radiation therapy were significantly less likely to have LF, with a hazard ratio of 0.57. The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4% for conventional-dose and 16.7% for high-dose radiation therapy (P < .0001). This difference held when only those with low-risk disease (n = 227; 58% of total) were examined: 28.2% for conventional and 7.1% for high dose (P < .0001). There was a strong trend in the same direction for the intermediate-risk patients (n = 144; 37% of total; 42.1% v 30.4%, P = .06). Eleven percent of patients subsequently required androgen deprivation for recurrence after conventional dose compared with 6% after high dose (P = .047). There remains no difference in OS rates between the treatment arms (78.4% v 83.4%; P = .41). Two percent of patients in both arms experienced late grade >/= 3 genitourinary toxicity, and 1% of patients in the high-dose arm experienced late grade >/= 3 GI toxicity. CONCLUSION This randomized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation. This was achieved without an increase in grade >/= 3 late urinary or rectal morbidity.
Purpose-To compare intensity-modulated photon radiotherapy (IMRT) with 3D-conformal proton therapy (3D-CPT) for early stage prostate cancer, and explore the potential utility of intensitymodulated proton therapy (IMPT).Methods-Ten patients were planned with both 3D-CPT (2 parallel-opposed lateral fields) and IMRT (7 equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, CGE for protons) to the prostate gland. Dose-volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with nonstandard beam configuration, and for IMPT assuming delivery with beam scanning.Results-At least 98% of the PTV received the prescription dose. IMRT plans yielded better dose conformity to the target, while proton plans achieved higher dose homogeneity, and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving over 70 Gy/CGE (V 70 ) were reduced, on average, by 34% with IMRT vs. 3D-CPT, while rectal V 70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties, for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V 70 was reduced by up to 35% compared to the standard lateral configuration, while the bladder V 70 increased by less than 10%.Conclusions-In the range over 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, while rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range below 50% of the target prescription was substantially lower with proton therapy.
Patients with locally persistent prostate cancer are at greater risk of DM. The higher initial hazard of DM is consistent either with an increased likelihood of subclinical micrometastases before treatment or with posttreatment tumor embolization. The prolonged time to appearance of DM in locally failing patients and the increasing hazard of DM over time is most consistent with a late wave of metastases from a locally persistent tumor.
BACKGROUND-Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam therapy (PBT).
We studied 161 prostate cancer patients treated by radical irradiation alone without endocrine therapy in whom pretreatment and posttreatment prostate specific antigen (PSA) values were measured, and who had a minimum followup of 2 years. Outcome was analyzed in an actuarial fashion using clinical disease-free survival and biochemical disease-free survival (freedom from an increasing PSA level or a PSA level of greater than 1.0 ng./ml. 2 years following irradiation) as end points. Of the patients 54% achieved a post-irradiation nadir value in the range 0 to 1.0 ng./ml. and 29% had a nadir value that was undetectably low (less than 0.5 ng./ml.). The likelihood of achieving these values was greater among patients with early stage than locally advanced tumors. For all T stages the likelihood of being disease-free at 4 years was substantially and significantly lower when PSA was used as an end point than when clinical evaluation alone was used: stages T1 and T2 (85 patients) 41% versus 71%, and stages T3 and T4 (76 patients) 15% versus 61%. For the whole group at 4 years clinical control was 67% but biochemical control was only 26% (p < 0.05). The likelihood of being free of biochemical evidence of persistent disease at 4 years was a function of the initial PSA value (PSA less than 4.0 in 81% of the cases, 4.1 to 10.0 in 43%, 10.1 to 20.0 in 31%, 20.1 to 50.0 in 6% and greater than 50.0 in 0%). For stages T1 and T2 cancer patients with an initial PSA level of less than 15 ng./ml. (67% of all early stage cases) this value was 65% and it was even higher (73%) when poorly differentiated tumors were excluded. When the initial PSA level for stages T1 and T2 tumors was greater than 15 ng./ml. the projected 4-year rate of freedom from biochemical failure was only 7%. For stages T3 and T4 cancer patients the corresponding figures were 39% for those with an initial PSA level of less than 15 ng./ml. and 0% for those with an initial PSA level of greater than 15 ng./ml. The prognostic power of the initial PSA level was independent of stage, grade, patient age and prior transurethral resection of the prostate in a multivariate analysis. An initial serum PSA level of more than 15 ng./ml. is, therefore, a powerful predictor of probable failure with conventional radiation therapy. Serum PSA monitoring is a sensitive detector of early relapse.(ABSTRACT TRUNCATED AT 400 WORDS)
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