PubMed Health⌕ Search

Biomedical subjects

A Pollack

Publications and source records attributed to A Pollack.

At least 91 records · Page 5Linked to original sources
PubMed1998

Relationship of ultrasound staging and bilateral biopsy positivity to outcome in stage T1c prostate cancer treated with radiotherapy.

OBJECTIVES: The strict definition of Stage T1c prostate cancer is that the tumor is not palpable on digital rectal examination (DRE) or seen on imaging studies such as ultrasound. The inclusion of ultrasound imaging was brought about without an understanding of the relationship between ultrasound upstaging and prognosis. We have also noticed that in clinical practice, treatment decisions are made on the basis of the finding of bilateral versus unilateral biopsy positivity. The objectives in this study were to determine the prognostic significance of upstaging by transrectal ultrasound (TRUS) to uT2 or uT3, and unilateral versus bilateral biopsy positivity in patients with Stage T1c cancer as determined by DRE (DRE-Stage T1c patients). METHODS: Between 1987 and 1995 there were 643 patients with DRE-Stage T1-T2 prostate cancer treated with external beam radiotherapy; 24 had T1a, 76 had T1b, 183 had T1c, 133 had T2a, 168 had T2b, and 59 had T2c. Of these, 135 DRE-Stage T1c patients underwent ultrasound staging and 122 underwent bilateral prostate biopsies. All had pretreatment prostate-specific antigen values (PSAs) available and no patient received adjuvant androgen ablation. The median pretreatment PSA was 9.1 ng/mL, median radiotherapy dose was 66.0 Gy, and median follow-up was 41 months. Post-treatment failure was defined as disease recurrence and/or two elevations in PSA on consecutive follow-up visits. RESULTS: The 5-year freedom from failure rate for DRE-Stage T1c patients (71%) was not significantly different from that of DRE-Stage T1b (65%) or DRE-Stage T2a (71%) patients. There was a trend (P = 0.1) toward a worse outcome for DRE-Stage T2b/T2c patients compared with DRE-Stage T1b/T1c/T2a patients. The distribution of DRE-Stage T1c patients by ultrasound staging was 29 with uT1c, 88 with uT2, and 18 with uT3 findings. Twenty percent of patients had bilateral positive biopsy specimens. In univariate and multivariate analyses, the only correlates of patient outcome were pretreatment PSA (P < or = 0.002) and isocenter dose (P = 0.03). TRUS upstaging had no effect on freedom from failure; uT1c patients had about the same risk of relapse or a rising PSA as uT2 or uT3 patients. Patients with bilateral positive prostate biopsy specimens had about the same prognosis as those with unilateral positive biopsy specimens. CONCLUSIONS: For patients with DRE-Stage T1c prostate cancer, the data indicate that ultrasound staging and bilateral biopsy positivity are not predictive of outcome for patients treated with external beam radiotherapy and treatment decisions should not be based on these parameters.

Actuarial Analysis↗
PubMed1998

Androgen ablation in addition to radiation therapy for prostate cancer: is there true benefit?

Prostate cancer patients may now be identified as having a high risk of failing single-modality treatment based on pretreatment prostate specific antigen (PSA), Gleason score, and palpable stage. In particular, a PSA greater than 20 ng/mL portends a biochemical failure rate of 50% to 80% when radiation therapy, surgery, or androgen ablation is administered individually. A number of randomized trials as well as retrospective data show that failure rates are significantly reduced by combining androgen ablation and radiation. The improved results, however, are complicated by the ability to salvage radiation alone-treated patients with androgen ablation and the possibility of less effective salvage (or no effective salvage in the case of permanent androgen ablation) for patients treated with androgen ablation plus radiation. Thus, survival, which is obscured by high rates of intercurrent deaths in this elderly population, is the most important end point in such studies. Two randomized trials, one from the Radiation Therapy Oncology Group (RTOG) and one from the European Organization for Research on Treatment for Cancer (EORTC), of radiation therapy plus adjuvant (as opposed to neoadjuvant) androgen ablation have reported survival gains over radiation therapy alone. In contrast, one neoadjuvant trial from the RTOG failed to show a survival benefit when androgen ablation was added to radiation therapy. In this study, however, androgen ablation was administered for only 4 to 5 months, which may be insufficient. The weight of the evidence to date indicates a true benefit with androgen ablation plus radiation therapy over radiation therapy alone. There are clearly many unanswered questions concerning the optimal timing of androgen ablation and radiation therapy (neoadjuvant versus adjuvant), length of time that androgen ablation should be administered (6 months versus 3 years versus permanent), type of androgen ablation (total androgen ablation or not), and appropriate patient population (definition of high risk). The planned future clinical trials will address many of these issues; however, the full potential of this approach requires an understanding of the fundamental mechanisms involved.

Androgen Antagonists↗
PubMed1998

Presentation, methods of diagnosis and therapy for pelvic recurrence following radical cystectomy for transitional cell carcinoma of the bladder.

PURPOSE: We evaluated the presentation, methods of diagnosis and treatment of pelvic recurrence following radical cystectomy for transitional cell carcinoma of the bladder. MATERIALS AND METHODS: We reviewed the records of 33 patients who underwent radical cystectomy for transitional cell carcinoma between May 1960 and August 1995 at our cancer center and who later had pelvic recurrence. RESULTS: The majority of patients underwent cystectomy for clinically advanced transitional cell carcinoma. Median time from cystectomy to recurrence was 10 months. Of the patients 25 were symptomatic (76%) at the time recurrence was diagnosed. Recurrence was discovered by digital rectal examination in 4 asymptomatic patients (12%) and by routine pelvic imaging in 2. Treatment included chemotherapy, surgery or radiation (alone or in combination). Of the 33 patients 29 died of progressive disease with a median survival of 7 months from the time of recurrence, and 4 remained free of disease at 7, 14, 26 and 95 months after local recurrence. Despite the poor survival rate following treatment 11 of 14 patients had complete resolution of symptoms following chemotherapy. CONCLUSIONS: The prognosis of patients with local recurrence is poor regardless of therapy. These recurrences are often symptomatic but careful post-cystectomy tumor surveillance, including digital rectal examination and pelvic imaging, provides an opportunity to diagnose local recurrences when they may be amenable to therapy. Systemic chemotherapy offers excellent palliation for symptomatic patients.

Aged↗
PubMed1998

The course of age-related macular degeneration following bilateral cataract surgery.

BACKGROUND AND OBJECTIVE: Progression of age-related macular degeneration (AMD) following cataract surgery has been described. The aim of this study was to investigate whether an uneventful postoperative maculopathic course in one eye (the first eye) may predict a similar prognosis for the fellow eye (the second eye). PATIENTS AND METHODS: Thirty-three patients with bilateral, similar, early AMD (defined by the presence of drusen and/or pigmentary abnormalities on fundal examinations and by the absence of late leakage as documented by fluorescein angiography) who had undergone unilateral cataract surgery, had had a stable postoperative maculopathic course following the first operation, and were scheduled for cataract surgery in the second eye were prospectively observed for at least 1 year after the second operation. The course of maculopathy of the second eye was compared with that of the first eye during the follow-up period of the second eye. RESULTS: A total of 9 of the second eyes (27.2%) showed progression to wet AMD. Of these, 1 patient (3%) had progression in both eyes and 8 patients (24.2%) had progression in the second eye only. The conditions of 2 of the first operated on eyes (6.1%) deteriorated (P < .05). Hypertension (P < .05), soft drusen (P < .01), and Nd:YAG laser capsulotomy (P < .05) were risk factors for development of wet AMD. CONCLUSION: In this study, 24.2% of the patients with early AMD who underwent bilateral cataract surgery and had an uneventful maculopathic course in the first eye had wet AMD in the second eye. Thus, patients with early AMD and soft drusen undergoing bilateral cataract surgery should be monitored for early detection of progression of maculopathy. Further prospective studies are needed to determine the course of maculopathy following cataract surgery.

Aged↗
PubMed1998

Locally recurrent soft tissue sarcoma of the extremities.

BACKGROUND: The management of locally recurrent extremity soft tissue sarcoma remains challenging. This study was undertaken to evaluate the long-term outcome after therapy for isolated locally recurrent soft tissue sarcoma (STS) of the extremity. METHODS: Between January 1, 1980, and December 31, 1990, 52 patients were treated at The University of Texas M. D. Anderson Cancer Center for locally recurrent extremity STS. The records of the subset of these patients (n = 36) with isolated local recurrence were examined to document clinicopathologic and treatment factors and to evaluate outcome using the end points of local recurrence-free, recurrence-free, and overall survival. RESULTS: Limb-sparing conservative surgery was possible in 24 patients (75%). Twelve (33%) of 36 patients were treated by surgery alone, 23 patients (64%) were treated with combined modality therapy (surgery plus radiation and/or chemotherapy), and 1 patient had radiotherapy only. Sixteen (44%) of 36 patients had no further recurrence of any type at a median follow-up of 58 months (range, 4 to 173 months). The 5-year actuarial local recurrence-free, recurrence-free, and overall survival rates were 72%, 45%, and 77%, respectively. CONCLUSIONS: Limb-sparing conservative surgery is possible in the majority of patients with isolated locally recurrent STS. Durable local control can be established with individualized local treatment strategies. These results support aggressive multimodality limb-sparing treatment approaches for these patients.

Adolescent↗
PubMed1998

NCCN urothelial cancer practice guidelines. National Comprehensive Cancer Network.

Urothelial tumors represent a spectrum of diseases with a range of prognoses. Once a diagnosis is established at any point on the urothelial tract, the patient remains at risk for developing a new lesion at a different or the same location, at a similar or more advanced stage. Continued monitoring for recurrence is an essential part of management, as most recurrences are superficial and can be managed by endoscopic means. Within each category of disease, more refined methods to determine prognosis and guide management, based on molecular staging, are under development. These methods are aimed at optimizing the individual patient's likelihood of cure and chance for organ preservation. For patients with more extensive disease, newer treatments typically involve combined-modality approaches using recently developed surgical procedures, or three-dimensional treatment planning for more precise delivery of radiation therapy. While these are not appropriate in all cases, they do offer the promise of an improved quality of life and prolonged survival. Finally, within the category of metastatic disease, a number of new agents have been identified that appear to be superior to those currently considered to be standard therapies. It is thought, therefore, that the treatment of urothelial tumors will evolve rapidly over the next few years, with improved outcomes for patients with all stages of disease.

Humans↗
PubMed1997

External beam radiotherapy dose response of prostate cancer.

PURPOSE: To determine the external beam radiotherapy dose response of palpable Stage T1-T4, mostly Nx, patients with adenocarcinoma of the prostate. METHODS AND MATERIALS: There were 938 men consecutively treated between 1987 and 1995 who had pretreatment prostate specific antigen (PSA) levels. Posttreatment failure was defined as disease recurrence and/or two elevations in PSA on consecutive follow-up visits. The radiotherapy technique consisted of a four-field box with a small four-field reduction after 46 Gy in 844 patients (total dose of 60-70 Gy) or with a six-field conformal boost after 46 Gy in 94 patients (total dose of 74-78 Gy). Neoadjuvant or adjuvant androgen ablation was not used in any patient. Median follow-up was 40 months. RESULTS: The mean and median radiotherapy doses for the entire group were 67.8 +/- 13.3 Gy (+/-SEM) and 66 Gy. The mean radiotherapy dose was higher in those who had Stage T3/T4 disease, Gleason scores of 8-10, or pretreatment PSAs of > 4 ng/ml. In general, patients with more aggressive pretreatment prognostic features were treated to higher doses; yet, those that relapsed or had a rising PSA were treated to significantly lower doses. Actuarial analyses were facilitated by dividing patients into three dose groups: < or = 67, > 67-77, and > 77 Gy. The actuarial freedom from failure rates at 3 years were 61, 74, and 96% for the low, intermediate, and high dose groups. Stratification of the patients by pretreatment PSA revealed that dose was a significant correlate of freedom from relapse or a rising PSA for those with PSAs > 4-10, > 10-20, and > 20 ng/ml. The only patients in which an improvement in outcome was not related to higher doses were those with a pretreatment PSA < or = 4 ng/ml. Dose was significantly associated with freedom from failure for Stage T1/T2 and Stage T3/T4 patients, as well as for those stratified by Gleason score. Multivariate analysis using Cox proportional hazards models showed that dose was an independent and highly significant predictor of relapse or a rising PSA. CONCLUSION: This retrospective review strongly indicates that radiotherapy dose to the prostate is critical to the cure of prostate cancer, even for favorable patients with pretreatment PSAs of > 4-10 ng/ml, Stages T1/T2, or Gleason scores of 2-6. Final confirmation awaits the results of our randomized trial.

Adenocarcinoma↗
PubMed1997

Retinoblastoma protein expression and radiation response in muscle-invasive bladder cancer.

PURPOSE: The retinoblastoma protein (pRB) is a key regulator of the G1 cell cycle checkpoint and has been implicated as having a role in G1 arrest and apoptosis induced by radiation damage. In this report we examine the association between pRB expression and radiation response in patients treated between 1960 and 1983 with preoperative radiotherapy (50 Gy in 25 fractions) followed 4-6 weeks later by radical cystectomy. The correlation of pRB to patient outcome and how this relationship is complimentary to that seen with p53 staining status is also described. METHODS AND MATERIALS: Immunohistochemical staining of pRB and p53 in paraffin-embedded tumor sections using WL-1 anti-RB and DO1 anti-p53 antibodies was considered adequate in 98 and 97 pretreatment tumor samples, respectively. There were 46 patients with clinical Stage T2, 28 with Stage T3a, and 24 with Stage T3b disease. The median age was 62 years and follow-up for those living was 85 months. RESULTS: Staining for pRB was negative in 30% of the cases. Correlations were observed between pRB negativity and high pretreatment apoptosis level (p = 0.06), locally advanced clinical stage (p = 0.01), increased clinical-to-pathologic downstaging (p = 0.014), and more pathologic complete responses (Path-CRs; p = 0.019). Several other factors were tested and were not associated with pRB status, including p53 expression. RB status was the only pretreatment prognostic factor in the univariate analyses that correlated with downstaging and was independently associated with Path-CR using multivariate logistic regression. Despite these significant relationships, no correlations with patient outcome were observed when the entire cohort was analyzed. Restriction of the analyses to Stage T3b patients, however, revealed that pRB negativity predicted for enhanced distant metastasis freedom (p = 0.006, log rank) and overall survival (p = 0.02). The overexpression of p53 also correlated with distant metastasis freedom and overall survival in Stage T3b patients. Patient outcome was best when RB negative and p53 negative staining were seen. CONCLUSION: Our results indicate that loss of RB function as measured by immunohistochemical staining is the strongest correlate of radiation response thus far recognized. Loss of RB expression also predicted for poor outcome in Stage T3b patients, which appeared to compliment the finding of normal p53 expression. While normal RB protein expression is usually associated with better patient outcome, other series have not examined patients treated with radiotherapy. The absence of pRB may be a useful marker for selecting patients for bladder preservation with radiotherapy, particularly when wild-type p53 is present.

Adult↗
PubMed1997

Management of unfavorable locoregional prostate carcinoma with radiation and androgen ablation.

BACKGROUND: This study attempted to define unfavorable locoregional prostate carcinoma and presents the results of treatment with combined radiation and androgen ablation for these patients. METHODS: Of a group of 938 men with clinically localized N0/NX disease treated with radiation alone, an unfavorable category included all men with prostate specific antigen (PSA) > 20 ng/mL and all men with 10 < PSA < or = 20 ng/mL but with Gleason's grade > 7. One hundred and eighty-five such men treated with radiation alone and an additional 100 men with similar disease received radiation with early androgen ablation. A second cohort was comprised of 229 men with lymphadenectomy proven pelvic lymph node metastases, with 185 receiving early androgen ablation alone and 44 receiving androgen ablation and local radiation. The outcomes, with recurrence or rising PSA as the endpoint, were compared among these various treatment groups using multivariate techniques. RESULTS: Disease outcome with the combined modality treatment was dramatically improved in both cohorts of men. For those with unfavorable N0/NX disease, the failure rate at 5 years decreased from 82% with only radiation therapy to 15% with combined treatment. Likewise, for patients with lymph node disease, the failure rate at 5 years decreased from 58% with only androgen ablation to 10% with combined treatment. For the whole group with unfavorable disease (unfavorable N0/NX and lymph node positive disease) the 6-year failure decreased from 71% with single modality treatment to 13% with bimodality treatment. There was a close relationship between the incidence of lymph node disease and prognostic categories and patients with otherwise unfavorable disease did not have their poor outlook ameliorated by undergoing a negative lymphadenectomy. CONCLUSIONS: Unfavorable locoregional prostate carcinoma can be recognized on the basis of pretreatment PSA level, T category, and Gleason's grade without specific evaluation of pelvic lymph node status. Combined local radiation and androgen ablation for patients with unfavorable disease results in a substantial improvement in disease control compared with that achieved by either modality alone. The authors found no improvement in survival because all groups of men had a normal life expectancy to at least 5 years.

Androgen Antagonists↗
PubMed1997

Serum testosterone levels after external beam radiation for clinically localized prostate cancer.

PURPOSE: To determine whether serum total testosterone levels change after external beam radiation therapy for localized prostate cancer. METHODS AND MATERIALS: Eighty-five men with clinically localized prostate cancer (T1-T3, N0/NX, M0) who underwent external beam radiation therapy without androgen ablation had pretreatment and 3-month posttreatment total serum testosterone levels determined by radioimmunoassay. Scattered doses to the testicles were measured with thermoluminescent dosimetry in 10 men. RESULTS: Pretreatment serum testosterone levels ranged from 185 to 783 ng/dl, with a mean of 400 ng/dl and a median of 390 ng/dl. The coefficient of variation was 30%. Postradiation 3-month testosterone levels ranged from 163 ng/dl to 796 ng/dl, with mean and median values of 356 ng/dl and 327 ng/ml, respectively. The coefficient of variation was 34%. The 3-month value was significantly lower than the pretreatment value (Wilcoxon paired p = 0.0001). The mean absolute fall was 94 ng/dl and the mean percentage fall was 9%. Although the fall in testosterone level was statistically significant, the difference was very small quantitatively. In contrast, serum prostate-specific antigen levels fell dramatically by 3 months after radiation. Testicular scattered doses ranged from 1.84 to 2.42 Gy, with a mean of 2.07 Gy for a prostatic tumor dose of 68 Gy. CONCLUSIONS: Although significant, the fall in serum testosterone level after radiation for localized prostate cancer was small and likely of no pathophysiologic consequence. It is unlikely that scattered testicular radiation plays any significant role in the genesis of this change in testosterone level, which most likely occurs as a nonspecific stress response.

Aged↗
PubMed1997

Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation.

PURPOSE: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. MATERIALS AND METHODS: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. RESULTS: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supraadditive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supraadditive effect when the combination was used. DISCUSSION: A supraadditive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and administration of androgen ablation and radiation.

Animals↗
PubMed1997

Quiescence in R3327-G rat prostate tumors after androgen ablation.

Androgen ablation is frequently used in conjunction with radiotherapy in the treatment of high-risk prostate cancer. Androgen ablation-induced cell kinetic changes could result in sub-additive (increased quiescence) or supra-additive (reduction in repopulation) interactions with radiotherapy. The cell kinetic changes were studied in R3327-G Dunning rat prostate tumors grown in vivo using double thymidine analogue labeling and flow cytometry, the terminal deoxynucleotidyl transferase-mediated nick end labeling assay for apoptosis, and measurements of tumor cell numbers. Tumors grown in intact and castrate male rats were continuously labeled for various periods of time with chlorodeoxyuridine and pulse-labeled with iododeoxyuridine 8 h before tumor removal. Androgen ablation resulted in a maximal reduction in labeling index (10 to 1.6%) and an increase in potential doubling time (Tpot; 6-42 days) within 3 days, which was related to a reduction in growth fraction (65% to <10%). In contrast, the length of S-phase was minimally altered (19 to 23 h). The response to androgen ablation involved little apoptosis and no necrosis, and Tpot was approximately the same as the tumor volume doubling time. Hence, the increase in Tpot was mainly the result of a shift to quiescence, and this shift occurred with minimal cell loss. Because quiescence is usually associated with radioresistance, these cell kinetic changes suggest that a sub-additive interaction may occur for some prostate cancers when androgen ablation and irradiation are given together.

Animals↗
PubMed1997

Prostate-specific antigen cancer volume: a significant prognostic factor in prostate cancer patients at intermediate risk of failing radiotherapy.

PURPOSE: Although the pretreatment serum prostate-specific antigen level (PSAL) is the single-most significant predictor of local and biochemical control in prostate cancer patients treated with radiotherapy, it is relatively insensitive for patients with a PSAL in the intermediate range (4-20 ng/ml). PSA density (PSAD) has been shown to be slightly more predictive of outcome than PSAL for this intermediate risk group; however, this improvement is small and of little use clinically. PSA cancer volume (PSACV), an estimate of cancer volume based on PSA, has recently been described and has been purported to be more significant than PSAL in predicting early biochemical failure after radiotherapy. We report a detailed comparison between this new prognostic factor, PSAL, and PSAD. METHODS AND MATERIALS: The records of 356 patients treated with definitive external beam radiotherapy for regionally localized (T1-4,Nx,M0) adenocarcinoma of the prostate were reviewed. Each patient had a PSAL, biopsy Gleason score, and pretreatment prostate volume by transrectal ultrasonography. The median PSAL was 9.3 ng/ml and 66% had Gleason scores in the 2-6 range. The median radiation dose was 66.0 Gy and the median follow-up for those living was 27 months. PSACV was calculated using a formula which takes into account PSAL, pretreatment prostate ultrasound volume, and Gleason score. The median PSACV was 1.43 cc. Biochemical failure was defined as increases in two consecutive follow-up PSA levels, one increase by a factor > 1.5, or an absolute increase of > 1 ng/ml. Local failure was defined as a cancer-positive prostate biopsy, obtained for evidence of tumor progression. RESULTS: The distributions of PSACV and PSAL were similar and, when normalized by log transformation, were highly correlated (p < 0.0001, linear regression). There was a statistically significant relationship between PSACV and several potential prognostic factors including PSAL, PSAD, stage, Gleason score, and pretreatment prostatic acid phosphatase (PAP). In univariate analyses, PSACV, PSAL, and PSAD proved to be the most significant predictors of both biochemical and local control. In multivariate analyses using Cox proportional hazards models with PSAL, PSAD, PSACV, and PAP as continuous variables, PSAL, PSACV, and Gleason score were significant in predicting biochemical control. Only PSAL was significantly correlated with local control. However, when these analyses were restricted to patients with intermediate PSALs (4-20 ng/ml), only PSACV was significant for predicting both biochemical and local control. CONCLUSION: PSACV was highly correlated with actuarial local and biochemical control and was superior to both PSAL and PSAD in predicting these outcomes in patients with PSALs between 4 and 20 ng/ml.

Adenocarcinoma↗
PubMed1997

The significance of DNA-ploidy and S-phase fraction in node-positive (stage D1) prostate cancer treated with androgen ablation.

BACKGROUND: The prognostic significance of primary tumor DNA-ploidy and S-phase fraction (SPF) was evaluated in patients treated with androgen ablation for regionally localized node-positive prostate cancer. METHODS: All patients were diagnosed with lymph node involvement by pelvic lymphadenectomy between 1984 and 1992 and were treated only with androgen ablation. Median follow-up was 45 months. Adequate material for DNA/nuclear protein flow cytometric analysis was available in 33 patients. RESULTS: The tumors were classified as diploid in 11, near-diploid in 4, tetraploid in 10, and aneuploid in 8 cases. Grouping the patients by nonaneuploidy (diploid and near-diploid and tetraploid) and aneuploidy revealed actuarial 4-year disease progression rates of 14 and 48% (log-rank, P = 0.04), and overall survival rates of 100 and 61% (P = 0.008); however, biochemical progression (rising prostate-specific antigen profile) rates were similar at around 70%. In contrast, SPF was not significantly related to any of the endpoints tested. Several other potential prognostic factors were examined and none correlated significantly with disease progression or survival. CONCLUSIONS: The biochemical progression rates for patients with nonaneuploid and aneuploid tumors were comparable and high, while the disease progression rates were higher and survival rates lower for those with aneuploid tumors. These data indicate that the lead time from biochemical to disease progression and death was shorter with aneuploidy. That these relationships were observed in such a small patient population attest to the strength of DNA-ploidy as a prognostic factor in this cohort.

Adenocarcinoma↗
PubMed1997

Prognostic factors for clinically localized prostate carcinoma: analysis of 938 patients irradiated in the prostate specific antigen era.

BACKGROUND: Pretreatment serum prostate specific antigen (PSA) level is a powerful prognostic factor for clinically localized prostate carcinoma. The traditional prognostic factors, T classification and Gleason score, appear to have been relegated to a minor position. This study was conducted to evaluate the relative prognostic roles of PSA, T classification, and Gleason score in a large cohort of men irradiated in the PSA era. METHODS: The authors analyzed the outcome for a group of 938 men with T1-T4, N0 or NX, M0 prostate carcinoma who received definitive external beam radiation therapy as their only initial treatment during the period 1987-1995. The T classifications were as follows: T1, 283 (30%); T2, 360 (38%); T3/T4, 295 (31%). Gleason scores were as follows: Gleason 2-6, 580 (62%); Gleason 7, 224 (24%); Gleason 8-10, 122 (13%). Pretreatment PSA levels (ng/mL) were as follows: PSA < or = 4, 167 (18%); PSA 4 to < or = 10, 363 (39%); PSA 10 to < or = 20, 259 (28%); PSA > 20, 149 (16%). At a mean follow-up of 43 months (range, 6-106 months), disease outcome specified as relapse/rising PSA, local recurrence, or metastasis was analyzed using univariate and multivariate techniques. RESULTS: The 6-year actuarial incidences of relapse/rising PSA, local recurrence, and metastases were 48%, 27%, and, 6%, respectively. In multivariate regression, pretreatment PSA level, T classification, and Gleason score were each independently highly significantly (P < 0.001) correlated with every endpoint. Pretreatment PSA level was the most significant variable for rising PSA and local recurrence, and T classification was the most significant variable for metastatic relapse. Using relapse/rising PSA as the endpoint, the authors formulated a highly significant 6-tier prognostic grouping based on PSA, T classification, and Gleason score, as follows: Category I: T1/T2, PSA < or = 4, and Gleason 2-6 (relapse rate, 6%); Category II: T1/T2, PSA < or = 4 and Gleason 7-10, or PSA 4 to < or = 10 and Gleason 2-7 (relapse rate, 30%); Category III: T1/T2, PSA 4 to < or = 10 and Gleason 8-10, or PSA 10 to < or = 20 and Gleason < 8 (relapse rate, 40%); Category IV: T3/T4, PSA < 10 (relapse rate, 46%); Category V: T3/T4, PSA 10 to < or = 20, and Gleason < 8 (relapse rate, 57%); Category unfavorable: any T, PSA > 20 and any Gleason, or PSA 10 to < or = 20 and Gleason 8-10 (relapse rate, 88%). CONCLUSIONS: The establishment of T classification and Gleason score as independent prognostic factors bridges an apparent gap between an older era and the current PSA era. PSA has supplemented, rather than supplanted, the utility of the traditionally established prognostic factors for clinically localized prostate carcinoma.

Aged↗
PubMed1997

Significance of downstaging in muscle-invasive bladder cancer treated with preoperative radiotherapy.

PURPOSE: The relationship between clinical-to-pathologic downstaging and patient outcome following preoperative radiotherapy was examined, focusing on the mechanism (selection vs. treatment effect) responsible for the benefit seen from such downstaging. METHODS AND MATERIALS: Three hundred and one patients were treated with preoperative radiotherapy plus cystectomy (PREOP) to a median dose of 50 Gy in 25 fractions between 1960-1983. These patients were compared to 225 patients treated with radical cystectomy, with or without chemotherapy (CYST), between 1984-1990. Multiagent chemotherapy was given to 68% of those in the CYST group and was not given to any in the PREOP group. Lymph node involvement was not formally evaluated in the PREOP group, while 20% had pathologic involvement in the CYST group. RESULTS: Clinical-to-pathologic downstaging (P < T stage) was found in 73% treated with PREOP and 29% treated with CYST (p < 0.0001, chi-square). The only factors that correlated with P < T staging for the PREOP and CYST groups when each was considered separately were clinical stage, blood urea nitrogen level, and creatinine level (p < 0.05, chi-square). Multivariate logistic regression revealed that treatment (PREOP vs. CYST) correlated independently with P < T staging (p < 0.0001). The relationship of actuarial local control to distant metastasis at 5 years in patients that were downstaged, as stratified by clinical stage and treatment, was then examined. Local control rates for P < T staged T2/T3a patients were independent of treatment (PREOP vs. CYST), while distant metastasis rates were significantly greater for those in the PREOP group. In contrast, P < T staged T3b patients in the PREOP group had significantly better local control and distant metastasis rates. CONCLUSIONS: Significantly higher P < T staging rates were observed with PREOP as compared to CYST, and this was a consequence of the radiotherapy given. The relationship of downstaging from radiotherapy to local control and distant metastasis was contingent on clinical stage. The results of Stage T2/T3a and T3b patients were divergent and supported treatment effect, rather than selection, as the mechanism consistent with the patient outcomes observed.

Adult↗
PubMed1997

Serum testosterone--a significant determinant of metastatic relapse for irradiated localized prostate cancer.

OBJECTIVES: To determine if the serum total testosterone concentration correlates with the outcome for men irradiated for clinically localized prostate cancer. METHODS: The outcome-local, nodal, distant metastatic, and biochemical--for 486 men with clinically localized prostate cancer treated by radiation and for whom testosterone levels were available was analyzed. No patient received adjuvant androgen ablation. Patient tumor stages were T1: 129 (27%); T2: 187 (38%); and T3/T4: 170 (35%). Median follow-up was 41 months. RESULTS: Pretreatment testosterone values ranged from 109 to 1121 ng/dL, with a mean of 417 ng/dL and a median of 398 ng/dL. The distribution of patients according to a four-tier testosterone grouping was testosterone level of 300 ng/dL or less, 108 (22%); testosterone level greater than 300 ng/dL but not more than 400 ng/dL, 141 (29%); testosterone level greater than 400 ng/dL but not more than 500 ng/dL, 123 (25%); and testosterone level greater than 500 ng/dL, 114 (23%). There were statistically significant but trivial correlations between testosterone level and age, T-stage, and acid phosphatase level. There was no correlation between testosterone and prostate-specific antigen (PSA) levels. There was a highly significant correlation between testosterone level and metastatic relapse. Patients with testosterone level greater than 500 ng/dL had a markedly higher 6-year metastatic rate (16%) than those with a testosterone level of 500 ng/dL or less (4%) (P = 0.001). In multivariate analysis, testosterone level was an independent determinant of metastatic relapse, second only to PSA level and of about the same power as T-stage. Gleason grade, although significant, was less so than testosterone level. The correlation of testosterone level to outcome appeared to be specific for metastatic relapse having no relation to local outcome. Likewise, high testosterone levels were not associated with acceleration of postradiation serum PSA kinetics. CONCLUSIONS: There is a highly significant correlation between pretreatment testosterone level and metastatic relapse in patients with clinically localized prostate cancer treated with radiation. As serum testosterone increases, so too does metastatic relapse. This relationship appears to take a decided turn for the worse at testosterone levels exceeding 500 ng/dL.

Aged↗