Identifying differences between biochemical failure and cure: incidence rates and predictors.
ABSTRACT Patients treated with radiation therapy (RT) for prostate cancer were evaluated to estimate the length of time required to document biochemical cure (BC) after treatment and the variables associated with long-term treatment efficacy.
2,100 patients received RT alone for localized prostate carcinoma (external-beam RT, n = 1,504; brachytherapy alone, n = 241; or brachytherapy + pelvic radiation, n = 355). The median external-beam dose was 68.4 Gy, and the median follow-up time was 8.6 years. Biochemical failure (BF) was defined according to the Phoenix definition.
Biochemical failure was experienced by 685 patients (32.6%). The median times to BF for low-, intermediate-, and high-risk groups were 6.0, 5.6, and 4.5 years respectively (p < 0.001). The average annual incidence rates of BF for years 1-5, 5-10,11-15, and 16-20 in low-risk patients were 2.0%, 2.0%, 0.3%, and 0.06% (p < 0.001); for intermediate-risk patients, 4%, 3%, 0.3%, and 0% (p < 0.001); and for high-risk patients, 10.0%, 5.0%, 0.3%, and 0.3% (p < 0.001). After 5 years of treatment, 36.9% of all patients experienced BF. The percentage of total failures occurring during years 1-5, 5-10, 11-15, and 16-20 were 48.7%, 43.5%, 6.5%, and 1.3% for low-risk patients; 64.0%, 32.2%, 3.8%, and 0% for intermediate-risk patients; and 71.9%, 25.9%, 1.1%, and 1.1% for high-risk patients, respectively. Increasing time to nadir was associated with increased time to BF. On multivariate analysis, factors significantly associated with 10-year BC included prostate-specific antigen nadir and time to nadir.
The incidence rates for BF did not plateau until later than 10 years after treatment, suggesting that extended follow-up time is required to monitor patients after treatment. Prostate-specific antigen nadir and time to nadir have the strongest association with long-term BC.
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ABSTRACT: This report describes treatment results of men with prostate cancer staged with a pelvic lymph node dissection. Disease freedom was defined by a prostate-specific antigen (PSA) level nadir of 0.5 ng/mL or less. Since 1984, 363 men with clinical Stage T1 or T2, surgical stage node-negative prostate cancer were simultaneously irradiated with a retropubic iodine 125 prostate implant followed by external-beam radiation. The average pretreatment PSA level was 13.6 ng/mL (median 8.5, range 0.3 to 188). Disease freedom was defined as the achievement and maintenance of a nadir of 0.5 ng/mL or less. Treatment failure was defined as a nadir of more than 0.5 ng/mL or a PSA rise above this level. The median follow-up is 5 years (average 5.5, range 1 to 12.5). For all men, the 5- and 10-year disease-free survival results are 78% and 65%. Of 201 men with a minimum 5-year follow-up, 140 (70%) are disease free. The 5-year disease-free survival rate by pretreatment PSA is 4.0 ng/mL or less, 93%; 4.1 to 10.0 ng/mL, 87%; 10.1 to 20.0 ng/mL, 72%; and greater than 20.0 ng/mL, 45%. The 10-year disease-free survival results of retropubic implantation, a technique considered a failure by many investigators, followed by external-beam radiation appear to be better than either technique given separately and are comparable to the results following radical prostatectomy. These results are valuable because they form a baseline that may be improved upon in the future by simultaneous irradiation using the transperineal implant technique.Urology 06/1997; 49(5):668-72. · 2.42 Impact Factor
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ABSTRACT: A reference range of prostate-specific antigen (PSA) values compatible with cure following radiotherapy (RT) for prostate cancer (PCa) has yet to be established. Various thresholds, as low as 0.5 ng/mL, have been used to define biochemical disease-free status. We report PSA profiles in 118 patients who were systematically biopsied following standard RT, with a minimum 4-year follow-up. One hundred eighteen patients were treated with standard external beam RT from May 1987 to October 1991, and were followed prospectively with transrectal ultrasound (TRUS)-guided biopsies and measurement of serum PSA levels. Stage distribution was as follows: T1b: 25 patients, T2a: 27 patients, T2b/c: 42 patients, T3: 23 patients, T4: 1 patient. Median follow-up for patients without clinical failure is 68 months (range 48 to 108). Treatment failures were categorized as biochemical (biochemical failure [chemF]: PSA level of 2.0 ng/mL or more and greater than 1 ng/mL over nadir), local (local failure [LF]: positive biopsy and PSA level greater than 2.0), and distant failure (DF). PCa recurred in 55% of patients: 38% LF (n = 45; 30 isolated and 15 with DF), 25% DF (n = 30; 15 isolated and 15 with LF), and 4% chemF (n = 5). Mean PSA nadir was 0.4 for patients with no evidence of disease (NED) and occurred at 33 months, 3.2 for LF at 17 months, 7.7 for DF at 12 months, and 1.4 for chemF at 24 months. After reaching the nadir, PSA in patients with recurrence followed first-order kinetics, rising exponentially over time. The mean PSA doubling time was 12.6 months for LF, 5.2 months for DF, and 21.8 months for chemF (P = 0.004). At last follow-up, the median PSA for patients without evidence of disease is 0.5 ng/mL. Four such patients had PSA values that rose to between 1 and 2 ng/mL for 5 to 38 months, but these eventually fell again to less than 1 ng/mL. Three patients had PSA values between 2 and 3 ng/mL, but 2 now have decreasing levels and the third has a rising level. All patients whose PSA levels rose to greater than 3 ng/mL exhibited a persistently rising pattern and ultimate tumor recurrence. There is a range of PSA values following RT for PCa that is compatible with cure. A definition of biochemical disease-free status at any absolute threshold of PSA level less than 3 ng/mL will overdiagnose failure in a significant proportion of patients. Patients with a PSA level between 1.5 and 3 ng/mL should be observed until there is unequivocal evidence of disease recurrence. In the absence of known biopsy status, PSA doubling time can be a useful indicator of whether failure is local or distant.Urology 05/1998; 51(4):566-72. · 2.42 Impact Factor
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ABSTRACT: To determine a prostatic-specific antigen (PSA) nadir value and time to nadir that predict a high probability of freedom from biochemical failure in men treated with external beam therapy for prostate cancer. Between January 1990 and March 1994, 228 men with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation with no prior or adjuvant hormonal therapy. All men had pre- and post-treatment serum PSA evaluations, and were followed up for at least 24 months, to ensure PSA nadir was reached. Biochemical failure was defined as three successive post-treatment rises in serum PSA, regardless of the magnitude of elevation. Overall, 4-year biochemical disease-free survival (BDFS) was 42%. PSA nadir was predictive of subsequent BDFS. For those whose serum PSA nadir was < or =1 ng/ml, 4-year BDFS was 70%, versus 12% for those with serum PSA nadir > 1 ng/ml (P = < 0.001). The 4-year BDFS for patients with time to nadir < or =1 year, was 28%, versus 58% for those with time to nadir > 1 year (P < 0.001). For patients with PSA nadir < or =1 ng/ml, 4-year BDFS was 75% for those with time to nadir > 1 year, versus 61% for those with time to nadir < or =1 year (P < 0.021). In multivariate analysis, PSA nadir(< or =1 ng/ml versus >1 ng/ml, and time to nadir (< or =1 year versus > year) were independent predictors of BDFS alone with pre-treatment PSA and Gleason score. Only those who achieved PSA nadir < or =1 ng/ml following external beam therapy have a favourable chance of lasting biochemical disease control, while those with nadir > 1 ng/ml have a high subsequent failure rate. The prognosis is better in patients with late time to nadir. In addition to PSA nadir, time to nadir, pretreatment PSA, and Gleason score were of independent prognostic significance.Radiotherapy and Oncology 08/1998; 48(2):203-7. · 4.52 Impact Factor