PSA doubling time in prostate cancer relapsed after endocrine therapy

PURPOSE: The PSA level of prostate cancer patients generally declines after endocrine therapy, but elevates when the cancer relapses in most cases. However, the rate of elevation differs with the case. We investigated the PSA doubling time (PSA-DT) of the prostate cancer patients whose PSA declined after endocrine therapy and later re-elevated, and investigated the relationship with other parameters. PATIENTS AND METHODS: We investigated 55 prostate cancer patients who underwent endocrine therapy between 1991 and 1998. Their PSA re-elevated continuously after their PSA fell below 10 ng/ml after the endocrine therapy as the first line treatment. First, the correlation coefficients with time and PSA were calculated in order to decide whether their PSA elevation was exponential or linear. PSA-DT was calculated thereafter, and compared with the clinical stage, pathological differentiation, clinical relapse style, time from the beginning of the therapy to PSA relapse, pre-treatment PSA value, and prognosis. The relationship between PSA-DT and each clinical parameter was tested using the Kruskal-Wallis test. Differences in survival rates and PSA-DT were calculated using the log-rank test. RESULTS: PSA elevated exponentially after cancer relapsed. PSA-DT in all cases ranged from 0.5 to 26.3 months, with an average of 4.4 +/- 4.8 (S.D.) months and the median was 2.5 months. PSA-DT was significantly (p < 0.01) short when the pre-treatment clinical stage was high, the time from the beginning of the therapy to PSA relapse was short, or the pre-treatment PSA value was high. PSA-DT tended to be short when the pre-treatment pathological differentiation was low, but not significantly. PSA-DT tended to be short when the cancer relapsed as distant metastasis rather than regional relapse, but not significantly. Prognosis from the initial treatment and PSA relapse was significantly poor when the PSA-DT was short. CONCLUSIONS: PSA elevated exponentially in the relapsed prostate cancer patients after the endocrine therapy. PSA-DT was distributed in a very wide range, and this value was considered to reflect the malignant potential and prognosis of the cancer. PSA-DT may be useful for determining the strategy after relapse.     

PSA-related parameters in prostate cancer relapsed after endocrine therapy

PURPOSE: Prostate cancer is generally controlled by endocrine therapy even in an advanced state, but relapse may occur in many cases. Generally, the prognosis of a relapsed case is poor, but the prognosis differs case by case. We experienced 74 cases of prostate cancer relapsed after effective endocrine therapy, and investigated the relationship between the PSA-related parameters, clinical stage and prognosis. PATIENTS AND METHODS: We investigated 74 prostate cancer patients whose PSA declined 10 ng/ml or lower by the treatment consisting of endocrine therapy, but relapsed later. Pre-treatment PSA, the value of PSA nadir, the period from the start of treatment to PSA nadir, the period from the start of treatment to relapse, PSA doubling time (PSA-DT) at relapse and PSA response to the second line therapy at relapse were calculated, and compared with the clinical stage and prognosis. The relationship between each PSA parameter and clinical stage was tested using the Kruskal-Wallis test and chi 2 test. Cancer-specific survival after relapse in stage D patients was calculated by the Kaplan-Meier method and differences in prognosis were tested using the Logrank test. RESULTS: Pre-treatment PSA was significantly (p < 0.01) high, while the period from the start of treatment to relapse (p < 0.05) and PSA-DT at relapse (p < 0.01) was significantly short as the stage progressed. According to PSA response to the second line therapy at relapse, the rate of CR + PR was significantly (p < 0.05) high in clinical stage B + C group compared to clinical stage D group. The prognosis after relapse was significantly poorer in patients with relapse within 10 months after start of treatment than in those with relapse later, and in patients whose PSA-DT at relapse was shorter than 2 months than in those with a longer PSA-DT. CONCLUSIONS: The period from the start of treatment to relapse, and PSA-DT at relapse were useful PSA-related parameters for predicting prognosis after relapse, and for determining the strategy of cancer therapy after relapse. Using these data, the physician can inform the family and the patient of the prognosis more accurately, so that they can adjust future plans.     

Prognostic factors for PSA relapse of prostate cancer after endocrine therapy

PURPOSE: Advanced prostate cancer responds well to endocrine therapy initially, but soon becomes refractory and has a poor prognosis. We analyzed the prognostic factors of prostate cancer responding well initially to endocrine therapy with lowering of serum prostate specific antigen (PSA) level but later showing PSA relapse. MATERIALS AND METHODS: In prostate cancer patients newly diagnosed from January 1992 to December 2004 at our institution, there were 93 patients in that the PSA level of 10 ng/ml or more before therapy initially dropped below 10 ng/ml by endocrine therapy, but showed PSA relapse thereafter. We investigated the relationship between clinical stage, pathological differentiation, initial PSA, duration between initiation of therapy and PSA nadir, the value of PSA nadir, duration between initiation of therapy and PSA relapse, PSA doubling time (PSA-DT) at relapse, PSA response three months after initiation of second line therapy and prognosis after PSA relapse. RESULTS: In Kaplan-Meier method, between all or some categories investigated showed significant difference in prognosis after PSA relapse. In multivariate analysis, the factors that significantly affected prognosis after PSA relapse were clinical stage, pathological differentiation, PSA nadir value, duration between initiation of therapy and PSA relapse and PSA response three months after initiation of second line therapy. CONCLUSION: We investigated the prognostic factors refractory to endocrine therapy. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and families.     

Progression after docetaxel-based chemotherapy in androgen-independent prostate cancer

OBJECTIVE: To assess the clinical pattern of progression and prostate-specific antigen doubling time (PSA-DT) after exposure to docetaxel-based chemotherapy in patients with androgen-independent prostate cancer (AIPC). PATIENTS AND METHODS: Fifty-five patients received docetaxel-based chemotherapy; data were collected retrospectively from three different departments. Progression was known in 44 (79%) and the PSA-DT was available in 33 patients. RESULTS: Of the 29 patients with soft-tissue and soft-tissue plus bone metastases, 22 (76%) developed soft-tissue progression. Among the 35 patients with bone and bone plus soft-tissue metastases, 27 (77%) had osseous progression. There was no difference between the PSA-DT at progression before and after docetaxel-based therapy (mean 3.1 vs 2.7 months, P = 0.592, Student's t-test.). However, the median (range) PSA-DT at progression after docetaxel-based therapy was 0.84 (0.3-4) months in patients with a PSA response, significantly shorter than the median of 3.1 (0.3-12) months of patients with no biochemical response (P = 0.002, Student's t-test). The PSA-DT dynamics at progression had no effect on survival (P = 0.63, log-rank test). CONCLUSION: The pattern of progression after docetaxel-based chemotherapy is predominantly osseous in patient with bone metastases and mostly soft-tissue in those with soft-tissue disease. Progression after docetaxel-based chemotherapy in AIPC does not modify the PSA-DT before docetaxel. Evaluation of a larger population is needed to assess the clinical relevance of PSA dynamics after docetaxel therapy.     

Deferred combined androgen blockade therapy using bicalutamide in patients with hormone-refractory prostate cancer during androgen deprivation monotherapy

OBJECTIVE: To assess the effect of adding bicalutamide on serum prostate-specific antigen (PSA) levels in patients with hormone-refractory prostate cancer (HRPC) during androgen deprivation monotherapy (ADMT). PATIENTS AND METHODS: Forty-four patients with HRPC were treated with deferred combined androgen blockade (CAB) therapy, administering bicalutamide 80 mg once daily. HRPC was defined biochemically as three consecutive rises in PSA level during ADMT. The treatment response was defined as a > or = 50% decline in PSA levels. Prognostic values of various pretreatment variables for responsiveness to deferred CAB were determined statistically. When the disease relapsed during deferred CAB, bicalutamide was discontinued and the patients were evaluated for the antiandrogen withdrawal syndrome (AWS). RESULTS: Of the 44 patients, 29 (66%) had a PSA response; the median PSA failure-free survival was 9.2+ months. Biopsy Gleason score was the only pretreatment variable predictive of a PSA response (mean Gleason score 7.9 in responders and 8.7 in nonresponders). The PSA doubling time (PSA-DT) was the only statistically significant variable of PSA failure-free survival in a multivariate analysis. The 1- and 2-year PSA failure-free survival rates were 43% and 31% in patients with a PSA-DT of >4 months, while it was 21% and none, respectively, in those with a PSA-DT of <4 months. Responders to deferred CAB had a statistically longer cancer-specific survival than nonresponders. None of 20 patients who were evaluated for AWS had the condition. CONCLUSIONS: Deferred CAB therapy using bicalutamide is effective in patients with progression during ADMT, particularly in those with lower Gleason score tumours or a longer PSA-DT. AWS after deferred CAB is uncommon.     

Global update on defining and treating high-risk localized prostate cancer with leuprorelin: a USA perspective--identifying men at diagnosis who are at high risk of prostate cancer death after surgery or radiation therapy

Prostate-specific antigen doubling time (PSA-DT) after surgery or radiotherapy (RT) is known to be a predictive factor for death from prostate cancer (prostate cancer-specific mortality, PCSM). An analysis of two multi-institutional databases, including 8669 men with prostate cancer treated with surgery or RT, found that a PSA-DT of <3 months, and the specific value of the PSA-DT when > or = 3 months, appeared to be surrogate endpoints for PCSM after surgery or RT. While many PSA failures occur after local therapy for localized prostate cancer, few of these patients go on to die from their disease, so it is important to identify other factors associated with PCSM, so that the subgroup of high-risk patients can be identified. An analysis was undertaken to determine whether patients at risk of PCSM could be identified using information available at diagnosis. The results showed that risk factors for PCSM were a PSA velocity of >2.0 ng/mL/year, a Gleason score of 8-10 and an increasing PSA level. However, the most important risk factor that had an impact on both PCSM and all-cause mortality was a PSA velocity of >2.0 ng/mL/year. PSA kinetics are being increasingly used in the setting of rising PSA levels after radical prostatectomy or RT, and several studies showed that the rate of increase in PSA level at the time of recurrence is closely associated with time to cancer death. A PSA-DT of <3 months is associated with a poor prognosis, and represents 15-20% of PSA failures in the general population and 6-7% of PSA failures in a screened population, such as those included in clinical trials. Better risk-assessment models are needed to help to identify at an early stage men who are at high risk of prostate cancer death and those who are at low risk, so that each subgroup can receive the most appropriate therapy for their disease.     

Correlation of initial PSA level and biopsy features with PSA-doubling time in early stage prostate cancers in Japanese men

OBJECTIVE: To distinguish good candidates for watchful waiting from those who need immediate treatment in localized prostate cancer. METHODS: Prostate specific antigen (PSA)-doubling time (DT) was calculated by a log-linear regression model for 78 patients with clinically localized prostate cancer (T1c: 47, T2a: 6, T2b: 21, and T3: 4) under surveillance. Median observation period was 37.5 months. The first 1-year PSA-DT was compared with the overall PSA-DT in 41 patients who had been under surveillance for more than 3 years. RESULTS: There was significant difference in the PSA-DT distribution between a pooled group of T1c and T2a and a group of T2b and T3 patients (median 58.8 versus 33.3 months, P = 0.0052). A combination of three parameters consisting of initial PSA level less than 10 ng/ml, WHO grade 1, one or two positive core per six to eight systematic biopsy cores with 50% or less cancer involvement significantly correlated with PSA-DT distribution in the T1c plus T2a group (P = 0.0034). The first year assessment of PSA-DT was identical to the overall assessment in 48.8%, 2 years or more in 36.6%, while it was 2 years or less (possibly over-estimated) in 14.6%. CONCLSION: PSA-DT can be predictable to some extent with the initial PSA level and biopsy features in early stage prostate cancers. Prospective study is needed to clarify whether temporary observation together with PSA-DT estimation is a safe strategy and is complementary to clinico-pathological parameters at diagnosis.     

Utility of prostate specific antigen doubling time in repeat biopsy for prostate cancer

PURPOSE: It is not rare that the repeat biopsy is performed when the initial biopsy was negative. However, there is not a clear indication for the repeat biopsy. We evaluated the utility of prostate specific antigen doubling time (PSA-DT) as indication for the repeat biopsy. MATERIALS AND METHODS: Of men 103 underwent repeat biopsy after initial negative prostate biopsy, 55 men who had three or more serial PSA measurements until repeat biopsy were evaluated. PSA-DT was calculated using a log-linear regression model and compared with other PSA-related parameters. RESULTS: Prostate cancer was diagnosed in 22 patients (40.0%). Mean PSA-DT in 55 patients was 59.3 months. Comparing of repeat positive biopsy group and negative group, PSA density (PSAD) and PSA velocity (PSAV) in the positive biopsy group were significantly greater than in the negative biopsy group. Age, serum PSA concentration at initial and repeat biopsy, PSA adjusted for volume of transition zone (PSATZ), free to total PSA ratio (%F/T) did not recognize significant differences between both biopsy groups. PSA-DT of positive biopsy group (35.1 months) was significantly shorter than that of negative biopsy group (76.5 months). None was diagnosed prostate cancer whose PSA-DT was longer than 96 months. CONCLUSION: When we considered prostate repeat biopsy, it was thought that PSA-DT could be one important material, but it was limitation for indication as to other PSA-related parameters.     

Prognostic and predictive factors in patients with androgen-independent prostate cancer treated with docetaxel and estramustine: a single institution experience

OBJECTIVES: To investigate potential prognostic and predictive factors in patients with androgen-independent prostate cancer (AIPC) treated with docetaxel chemotherapy. METHODS: This analysis included 94 consecutive AIPC patients who were treated between March 2001 and May 2006 with biweekly docetaxel 45 mg/m(2) (day 2) and estramustine 140 mg three dimes daily (days 1-3). RESULTS: Prostate-specific antigen (PSA) responses were observed in 45 of 84 evaluable patients (53%), whereas objective responses were observed in 16 of 40 patients with measurable disease (40%). Median survival (OS) was 16.2 mo (95% confidence interval [CI], 12.9-19.4) and median time to PSA progression (TTP) 5.0 mo (95%CI, 3.6-7.1). OS was independently associated with pain score baseline PSA and weight loss. Patients with only extraosseous disease had higher PSA response rate (87% vs. 49%, p=0.014) and superior TTP compared with patients with bone metastases with or without extraosseous disease (7.3 vs. 4.3 vs. 4 mo, p=0.002). Concurrent bone and extraosseous metastases were associated with worse prognosis compared with each site alone (median OS: 12.3 vs.19 vs.18.3 mo, p=0.007). CONCLUSIONS: Among patients with AIPC treated with biweekly docetaxel and estramustine, baseline PSA >100, existence of pain, weight loss, and simultaneous extraosseous and bone disease were associated with worse prognosis. Extraosseous metastases seem to be more sensitive than bone disease to this chemotherapy.     

Bone metastases in osteosarcoma patients treated with neoadjuvant or adjuvant chemotherapy: the Rizzoli experience in 52 patients

INTRODUCTION: There have been no large-scale studies reporting the outcome of patients with osteosarcoma who first relapse with bone metastases, but there have been several case reports describing a much poorer prognosis for these patients than for those who relapse with lung metastases. METHODS: We compared 52 patients with skeletal metastases as first relapse after neoadjuvant or adjuvant treatment for osteosarcoma of the extremity given at our institution between 1972 and 1999 with 371 contemporary patients treated with the same chemotherapy protocols, who first relapsed with lung metastases. RESULTS: We found that the 52 patients with bone metastases had a higher rate of local recurrences (36% vs. 6%), a lower rate of remission (35% vs. 77%), and lower rates of 5-year event-free survival (11% vs. 27%) and overall survival (13% vs. 31%) (p < 0.01 for all comparisons). INTERPRETATION: The prognosis of patients who relapse with bone metastases--unless they have a single late-appearing metastasis--is worse than the prognosis of patients who first relapse with lung metastases. There was no difference in outcome between patients with single, resectable and late-appearing skeletal metastases and patients relapsing in the lung.     

Prostate specific antigen response to mitoxantrone and prednisone in patients with refractory prostate cancer: prognostic factors and generalizability of a multicenter trial to clinical practice

PURPOSE: We determine prostate specific antigen (PSA) response and durability, and prognostic factors associated with response and survival in patients with symptomatic hormone refractory prostate cancer treated with mitoxantrone and prednisone at a single institution. We then compare the results with those of a randomized phase III clinical trial. MATERIALS AND METHODS: A retrospective review of all 133 patients treated with mitoxantrone and prednisone at Princess Margaret Hospital since 1994 was performed. PSA response and duration, and overall survival were determined as well as the influence of baseline factors on these outcome parameters. Results were compared to those for patients randomized to receive mitoxantrone and prednisone in the Canadian clinical trial which demonstrated palliative benefit of this regimen. RESULTS: Patients treated after trial closure had shorter survival (p = 0.003) but represented a poorer prognosis cohort. PSA response of the trial and post-trial cases was 34% and 28%, respectively (p = 0.36), and median duration of response was 118 and 175 days or greater, respectively. Factors predictive of PSA response in the non-trial cohort were longer time from diagnosis of prostate cancer (p = 0. 027) and higher baseline PSA (p = 0.013). Factors predictive of increased survival in both groups were younger age (p <0.04), better baseline Eastern Cooperative Oncology Group performance status (p <0. 02), and higher hemoglobin (p 相似文献   

Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy

OBJECTIVES: Preoperative low serum testosterone (TS) level has been reported to be associated with adverse pathologic results in patients with clinically localized prostate cancer (pCA) treated with radical prostatectomy (RP). However, prior studies failed to show prognostic impact of preoperative low TS in these patients. The aim of this study was to investigate the relationship between preoperative TS and prostate-specific antigen (PSA) failure in these patients. METHODS: Of 304 patients diagnosed with clinically localized pCA who had been treated with RP alone, 272 patients whose preoperative TS level had been measured were eligible for this analysis. Postoperative TS levels were also available in 222 of the 272 patients. Cox proportional hazard model was used to elucidate factors predictive for PSA failure. RESULTS: Of the 272 patients 49 had low (< 300 ng/dl) and 223 had normal preoperative TS level. In a stepwise multivariate analysis, preoperative TS (p = 0.021) was an independent and significant predictor of PSA failure along with RP Gleason score (p = 0.006), surgical margin status (p = 0.0001), and PSA (p = 0.0001). Five-year PSA failure-free survival rate of the patients with preoperative low TS (67.8%) was significantly worse than that with normal TS (84.9%) (p=0.035). Serum TS levels increased significantly after RP (p < 0.0001). The increment of TS level in preoperative low TS group was significantly greater than that in preoperative normal TS group (p = 0.0003). CONCLUSIONS: The current results demonstrated that preoperative TS level is an independent and significant predictor of PSA failure after RP in patients with clinically localized pCA.     

Orchidectomy following failure of antiandrogen monotherapy in patients with metastatic prostate cancer

OBJECTIVE: Patients with metastatic prostate cancer who are initially treated by oral antiandrogens and then have progressive disease may be offered surgical castration as a second-line treatment. Twenty-eight such patients were reviewed to determine the outcome in terms of secondary PSA response, symptomatic relief and disease-specific survival. MATERIALS AND METHODS: Retrospective chart-based review of patients undergoing bilateral scrotal orchidectomy after failure of antiandrogen monotherapy. RESULTS: Patients who had a >50% reduction in PSA at 12 weeks' postorchidectomy had significantly greater duration of PSA response and disease-specific survival. 64% of patients who had bone pain prior to orchidectomy had some relief of symptoms postoperatively. No prognostic indicators of improved survival were identified. CONCLUSION: Orchidectomy as a secondary hormonal treatment following relapse on antiandrogens does produce a response in terms of PSA level and symptoms in some patients.     

Prostate-specific antigen doubling time among Japanese men in an annual health screening program

BACKGROUND: Prostate-specific antigen doubling time (PSA-DT) has been studied as a parameter reflecting the biological doubling rate of clinically localized prostate cancer treated expectantly. With the use of PSA-DT, we studied the natural history of PSA changes among Japanese men in a health screening program. METHODS: Between July 1994 and December 2002, a cohort of 1995 men aged 40-79 years underwent a total of 5700 PSA measurements in an annual multiphasic health screening program. Prostate-specific antigen doubling time was calculated using a log-linear regression model for 994 (49.8%) men who had three or more serial PSA measurements with a mean follow-up of 46.2 months. RESULTS: Of the 994 men, 192 (19.3%) had a PSA-DT of less than 10 years and 12 (1.2%) had a PSA-DT of less than 2 years. Median PSA-DT in 14 men with a subsequent diagnosis of prostate cancer was 41.6 months (range, 12.2 to stable). A log-linear model statistically fitted 65 of 180 non-cancer patients with a PSA-DT of less than 10 years. The percentages of statistically fit cases increased with higher baseline PSA (5.3%, 7.7% and 8.7% among men with <1.0, 1.0-1.99 and 2.0-3.99 ng/mL, respectively) and older baseline age (3.7%, 8.5% and 6.9% among ages 40-49, 50-59 and 60 or older, respectively). CONCLUSION: In a small but significant portion of men, PSA increases exponentially when it is still less than 4.0 ng/mL, with a PSA-DT of less than 10 years. The clinical significance of this finding should be evaluated by a prospective screening including biopsy.     

Azacitidine favorably modulates PSA kinetics correlating with plasma DNA LINE-1 hypomethylation in men with chemonaïve castration-resistant prostate cancer

Background

Azacitidine is a hypomethylating agent that activates genes repressed by promoter methylation. Preclinically, demethylating agents reverse resistance of prostate cancer to androgen ablation. A phase II trial evaluated azacitidine for men with castration-resistant prostate cancer (CRPC) progressing on combined androgen blockade (CAB).

Methods

Chemonaïve patients with CRPC on CAB and PSA-doubling time (DT) < 3 months were eligible. The primary endpoint was prolongation of PSA-DT to ≥3 months. Correlation of biologic activity (fetal hemoglobin, plasma DNA LINE-1 methylation) with prolongation of PSA-DT was tested. CAB was continued and azacitidine 75 mg/m² was administered subcutaneously on days 1–5 of each 28-day cycle up to 12 cycles or until clinical progression/intolerable toxicities.

Results

Thirty-six patients were enrolled, 80.6% had metastatic disease, and 34 were evaluable. A PSA-DT ≥ 3 months was attained in 19 patients (55.8%). Overall median PSA-DT was significantly prolonged compared to baseline (2.8 vs. 1.5 months, P < 0.01). Fourteen patients had some PSA decline during therapy and 1 patient had a ≥30% decline compared with baseline. The median clinical progression-free survival was 12.4 weeks. Grade 3 toxicities included fatigue (12%), and neutropenia (6%), with 4 patients discontinuing due to toxicities. A trend in decreasing plasma DNA LINE-1 methylation was seen with longer treatment duration (P = 0.06), which significantly correlated with prolongation of PSA-DT (P = 0.02).

Conclusions

Azacitidine favorably modulates PSA kinetics in chemonaïve CRPC that correlates with decreasing plasma DNA LINE-1 methylation. Given the excellent tolerability, further development of azacitidine for CRPC may be warranted, with exploration of combination regimens.     

Changes in free and free-to-total prostate specific antigen after androgen deprivation or chemotherapy in patients with advanced prostate cancer

PURPOSE: To provide preliminary data on whether the diagnostic role of serum prostate specific antigen (PSA) in assessing the response to treatment is improved by concomitant free PSA evaluation both markers were evaluated in 42 patients with advanced prostate cancer who received hormonal therapy and 57 with hormone refractory disease who received chemotherapy. MATERIALS AND METHODS: PSA was assessed at baseline and every 3 months during treatment. Free PSA was assessed in stored serum samples obtained at baseline and at maximum PSA decrease. Free PSA was not measurable in 17 patients who received androgen deprivation (40.5%) and 2 who received chemotherapy (3.5%) because it was less than 1.5 ng./ml. RESULTS: Of the 21 patients with greater than 50% PSA decrease after hormonal therapy free-to-total PSA increased in 12 (57.2%) and decreased in 9 (42.9%). Of the 20 patients with PSA response after chemotherapy free-to-total PSA increased in 18 (90.0%) and decreased in 2 (10.0%). Free-to-total PSA increased in 12 of the 20 patients (60.0%) with PSA stabilization after chemotherapy. Patients with an increase in free-to-total PSA after chemotherapy had greater survival compared to those with a decrease or no change (19.8 versus 15.5 months, respectively, p <0.03). CONCLUSIONS: These data suggest that an effective cytotoxic regimen mainly affects the protein bound PSA fraction. The absence of a clear predominant pattern of free-to-total PSA in patients with PSA response to hormonal therapy and the high percentage of hormone sensitive patients in whom free PSA was not assessable at maximum PSA decrease suggest that free PSA evaluation is less useful in prostate cancer patients undergoing androgen deprivation.     

Bone metastases in osteosarcoma patients treated with neoadjuvant or adjuvant chemotherapy The Rizzoli experience in 52 patients

Introduction?There have been no large-scale studies reporting the outcome of patients with osteosarcoma who first relapse with bone metastases, but there have been several case reports describing a much poorer prognosis for these patients than for those who relapse with lung metastases.

Methods?We compared 52 patients with skeletal metastases as first relapse after neoadjuvant or adjuvant treatment for osteosarcoma of the extremity given at our institution between 1972 and 1999 with 371 contemporary patients treated with the same chemotherapy protocols, who first relapsed with lung metastases.

Results?We found that the 52 patients with bone metastases had a higher rate of local recurrences (36% vs. 6%), a lower rate of remission (35% vs. 77%), and lower rates of 5-year event-free survival (11% vs. 27%) and overall survival (13% vs. 31%) (p < 0.01 for all comparisons).

Interpretation?The prognosis of patients who relapse with bone metastases—unless they have a single lateappearing metastasis—is worse than the prognosis of patients who first relapse with lung metastases. There was no difference in outcome between patients with single, resectable and late-appearing skeletal metastases and patients relapsing in the lung.     

Usefulness of extension of disease as a prognostic factor in relapsed prostate cancer patients of stage D

OBJECTIVE: The prognosis of prostate cancer has been evaluated by clinical stage or pathological grade. PSA parameters including PSA density and PSA doubling time have not always precisely reflected the prognosis of prostate cancer. The aim of this study was to evaluate PSA parameters and extension of disease (EOD) grade as prognostic factors for relapsed prostate cancer. METHODS: The relationship between PSA parameters or EOD grade, and survival of 29 stage D patients with relapsed prostate cancer after initial hormone therapy was examined. RESULTS: Only EOD grade was an independent prognostic factor, even for cause-specific survival period and survival period after relapse. CONCLUSION: EOD grade was a significant prognostic factor, and in particular, very useful as a prognostic factor for patients with bone metastasis. PSA value was not always associated with tumor volume, and therefore it is not an independent prognostic factor.     

Oral estramustine phosphate and oral etoposide for the treatment of hormone-refractory prostate cancer

BACKGROUND: The purpose of the present study was to evaluate the antitumor activity and toxicity of oral estramustine phosphate (EMP) in combination with oral etoposide in patients with hormone-refractory prostate cancer. METHODS: Twenty patients with adenocarcinoma of the prostate that progressed after one or more regimens of androgen-deprivation therapy were enrolled into this trial. Oral EMP was administered twice daily, for a total daily dose of 560 mg, and oral etoposide (50 mg/bodyweight per day) was given on days 1-21 and was stopped on days 22-35. Treatment was continued until evidence of disease progression appeared or two consecutive rises in the prostate-specific antigen (PSA) value were observed. RESULTS: Ten of 20 patients showed a decrease of 50% or greater in the PSA value from initially elevated PSA levels after therapy. The median progression-free duration and 2 year cause-specific survival rate of these 10 patients were 208 days (range 71-693 days) and 67.5%, respectively. There were no significant differences in age, pretreatment PSA value, duration from initial treatment to relapse, prior therapy or survival between patients who had a decrease of 50% or greater in PSA values after this combination therapy and those who did not. The main toxicities (> or =grade 2) were anemia, leukocytopenia, thrombocytopenia, gastrointestinal and hepatic disorders, which occurred in 40, 15, 10, 15 and 5% of patients, respectively. CONCLUSIONS: The combination of oral EMP and etoposide is considered to be a well-tolerated outpatient treatment regimen for patients with hormone-refractory prostate cancer and the therapy deserves further investigation.     

Significance of prostate-specific antigen-doubling time on survival of patients with hormone refractory prostate cancer and bone metastasis: Analysis on 56 cases of cancer-specific death

OBJECTIVE: Most of the metastatic diseases initially respond to maximum androgen blockade, but then relapse and lose response, and finally die. After relapse, the disease progresses in various courses. The present study was aimed to establish the predicting factors influencing the survival period of patients at prostate-specific antigen (PSA) relapse (entering the hormone refractory state). MATERIALS AND METHODS: Fifty-six patients with prostate cancer and bone metastasis, who were treated during the entire disease period at the same hospital and died were studied. To calculate PSA-doubling time, assay of PSA was carried out every 3 months or less. RESULTS: The period between PSA relapse and death was related with PSA-doubling time at relapse, nadir PSA and the period between the start of treatment and PSA relapse. The PSA-doubling time of 2 months or less at relapse was suggestive of a poor outcome. Final PSA-doubling time was not correlated with the survival period after PSA relapse. CONCLUSION: The PSA-doubling time at relapse is one of the relevant factors for predicting the survival period after PSA relapse.