Hodgkin's disease with lymphocyte predominance: long-term results based on current histopathologic criteria.

PURPOSE: To define the disease course, therapeutic strategies, patterns and rates of relapse and causes of death for patients with Hodgkin's disease with lymphocyte predominance (LPHD) and to assess prognostic factors including nodular and diffuse histologic patterns. PATIENTS AND METHODS: The records of all previously untreated patients with LPHD who received initial treatment at the University of Texas M. D. Anderson Cancer Center (UTMDACC) from 1960 through 1992 were reviewed. Clinical and histopathologic characteristics, specifically nodular and diffuse LPHD, and treatment groups were assessed by overall and relapse-free survival, patterns of relapse, and causes of death. RESULTS: Of 70 patients, 58 (83%) had nodular LPHD and 12 (17%) had a diffuse pattern: clinical characteristics were similar between the two subtypes. The median age of all patients was 25 years, 79% were male, 96% presented with stage I or II disease and 93% were free of B symptoms. Laparotomy (23 patients) failed to upstage any patient with a negative lymphogram. With a median follow-up of 12.3 years for alive patients, 19 (27%) patients have relapsed. All 3 relapses among the patients with diffuse subtype occurred within 3 years while 9 of 16 relapses occurred after 5 years with nodular subtype. However, we did not detect any statistically significant difference in relapse free survival or survival between the subtypes in our patient population. There was some suggestion that patients aged 40 and older experienced shorter survival; no other pretreatment characteristics were noted to be associated with relapse free survival or survival. Though there were no relapses within the radiation fields, no effect of extent of radiation therapy on relapse rate was observed. Thirteen (19%) patients have died, 6 (8.6%) of whom succumbed to LPHD. Two patients developed diffuse large cell lymphoma. CONCLUSIONS: Patients with LPHD usually present with localized and asymptomatic disease. Laparotomy is unnecessary if the lymphogram is negative. Nodular histology occurred in the majority of patients. Though all relapses from diffuse subtype occurred within 3 years in contrast to some late relapses observed for nodular subtype, there was no statistically significant difference in relapse free survival or survival between the subtypes. The extent of irradiation had no effect on relapse free survival or survival. We could not find any evidence that LPHD should be treated any different from the classical Hodgkin's disease at this point despite suggestions that it be classified as a non-Hodgkin's B-cell lymphoma.

Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered prognostic factors with combined modality therapy.

BACKGROUND: Lymphoma of the nasal cavity and paranasal sinuses is a rare presentation of extranodal lymphoma with a natural history that is not well characterized in this era of combination chemotherapy. The goals of this retrospective study were 1) to define the natural history of sinonasal lymphomas; 2) to compare the results of radiation therapy (XRT) alone with those of combined modality therapy (CMT) in the treatment of patients with lymphoma of the nasal cavity and paranasal sinuses; and 3) to define prognostic factors for each treatment. METHODS: Between 1947 and 1993, 70 patients with newly diagnosed lymphoma of the nasal cavity and paranasal sinuses were treated. The Ann Arbor stages were: Stage IE: 42 patients; Stage IIE: 14 patients; Stage IIIE: 2 patients; and Stage IV: 12 patients. The distribution of T classifications of the primary tumors was as follows: T1: 2 patients; T2: 16; T3: 18; and T4: 34. Greater than 90% of the patients had intermediate grade lymphoma (Working Formulation), and none had follicular lymphoma. Twenty-eight patients received XRT alone, and 42 received CMT. RESULTS: The actuarial 5-year freedom from progression (FFP) and overall survival (OS) rates for the entire group were 57% and 52%, respectively. For patients with localized disease (Stages IE and IIE) receiving CMT, the actuarial 5-year FFP and OS were 83% and 67%, respectively. In multivariate analysis, treatment with CMT (P = 0.0005) and stage (IE vs. IIIE-IV) (P = 0.0001) were associated with improved FFP. In the group of patients receiving XRT, extent of disease (Stage IE, T1-3 vs. Stage IE, T4 vs. Stage IIE-IV) (P = 0.0001) was the only clinical characteristic associated with improved FFP in multivariate analysis. For patients receiving CMT, International Index (0 vs. 1-3 vs. 4, 5) (P = 0.0001) was the only significant factor predictive of improved FFP in multivariate analysis. One patient failed in the central nervous system (CNS) after initial therapy as a result of a radiation therapy marginal miss. CONCLUSIONS: In a Western population, patients with localized lymphoma of the nasal cavity and paranasal sinuses have a favorable prognosis when treated with CMT. FFP is significantly improved by treatment with CMT. For patients treated with XRT, extent of disease is the strongest predictor of outcome. International Index is the most significant prognostic factor for patients receiving CMT. Failure in the CNS is rare after initial therapy and is associated with local failure.

Prostate-specific antigen and radiation therapy for clinically localized prostate cancer.

PURPOSE: This study was undertaken to: (a) define the prognostic significance of pretreatment serum prostate-specific antigen (PSA) levels in localized prostate cancer treated with radiation; (b) define the prognostic usefulness of postradiation PSA levels; (c) evaluate the outcome of radiation using PSA as an endpoint. METHODS AND MATERIALS: Disease outcome in 707 patients with Stages T1 (205 men), T2 (256 men), T3 (239 men), and T4 (7 men), receiving definitive external radiation as sole therapy, was evaluated using univariate and multivariate techniques. RESULTS: At a mean follow-up of 31 months, 157 patients (22%) developed relapse or a rising PSA. Multivariate analysis revealed pretreatment PSA level to be the most significant prognostic factor, with lesser though significant contributions due to Gleason grade (2-6 vs. 7-10) and transurethral resection in T3/T4 disease. The following four prognostic groupings were defined: group I, PSA < or = 4 ng/ml, any grade; group II, 4 < PSA < or = 20, grades 2-6; group III, 4 < PSA < or = 20, grades 7-10; group IV, PSA > 20, any grade. Five-year actuarial relapse rates in these groups were: I, 12%; II, 34%; III, 40%; and IV, 81%. Posttreatment nadir PSA was an independent determinant of outcome and only patients with nadir values < 1 ng/ml fared well (5-year relapse rate 20%). Using rising PSA as an endpoint the 461 patients with T1/T2 disease had an actuarial freedom from disease rate of 70% at 5 years, which appeared to plateau, suggesting that many were cured. No plateau was evident for T3/T4 disease. CONCLUSION: Pretreatment serum PSA is the single most important predictor of disease outcome after radiation for local prostate cancer. Tumor grade has a lesser though significant prognostic role. Postirradiation nadir PSA value during the first year is a sensitive indicator of response to treatment. Only nadir values < 1 ng/ml are associated with a favorable outlook. A significant fraction of men with T1/T2 disease may be cured with radiation. There was no evidence for a cured fraction among patients with T3/T4 disease.

The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer--T, N, or M?

PURPOSE: Prostate-specific antigen (PSA) is an important marker for prostate cancer and has been shown to be secreted from the primary tumor and from metastases. However, the relative contribution of the primary and micrometastatic disease to the serum level of PSA in patients with clinically localized disease has not been delineated. This study addresses the source of pretreatment serum PSA in patients with clinically localized disease. METHODS AND MATERIALS: The fall in serum PSA level following radical prostatectomy (280 patients; 105 T1, 165 T2, 10 T3) or definitive radiotherapy (427 patients; 122 T1, 147 T2, 158 T3/T4) was analyzed with the assumption that any fall in PSA following local treatment reflects the fraction of PSA produced in the prostate and its primary tumor. RESULTS: Serum PSA level became undetectable in 277 of the 280 (99%) patients within 6 months of radical prostatectomy. The three patients who did not achieve undetectable levels had postsurgical values < or = 0.9 ng/ml. Following definitive radiotherapy, nadir serum PSA values were between < or = 0.3 and 20.3 ng/ml, with mean and median values of 1.9 and 1.2 ng/ml, respectively. Nadir PSA was undetectable in 52 patients (12%). Four patients' PSA did not fall, but rose from the start, and each developed metastatic disease within 9 months, and in each metastases appeared to contribute to pretreatment serum PSA. In the remaining patients, the maximal factor by which PSA fell to its nadir was higher the higher the pretreatment PSA level. We present arguments that this is most consistent with the hypothesis that virtually all detectable pretreatment serum PSA derives from the primary tumor. Confirmatory evidence that little of the pretreatment serum PSA came from metastases was obtained by extrapolating the rising PSA profile in 97 patients back to pretreatment time. Back-extrapolated PSA contributed a mean of 7% and a median of 5% to the pretreatment serum value. Because such back-extrapolated values estimate the potentially maximal micrometastatic contribution, metastatic disease at diagnosis contributes little to pretreatment serum PSA. CONCLUSION: In patients with clinically localized prostate cancer, putative micrometastatic disease contributes negligibly to the pretreatment serum PSA level even when the latter is high. Most likely such patients, when they have metastases, have a very low metastatic burden.

Serum prostate-specific antigen after radiation therapy for clinically localized prostate cancer: prognostic implications.

PURPOSE: Serum prostate-specific antigen (PSA) levels following definitive radiation for prostate cancer are increasingly recognized as the most sensitive means to monitor disease status. However, beyond general agreement that patients fare poorly when posttreatment PSA levels fail to normalize, many questions relative to postirradiation PSA remain unanswered. This study evaluates the potential prognostic value of postirradiation PSA in a large cohort of patients followed with serial PSA determinations. METHODS AND MATERIALS: We analyzed disease outcome in 427 patients with clinical stages T1 (122 men), T2 (147 men), T3 (152 men), and T4 (six men) prostate cancer receiving definitive external radiation as sole therapy and followed for times ranging from 9-73 months (median 30 months) with a total of 2260 posttreatment PSA values. RESULTS: Excluding three patients who died due to intercurrent illness without a posttreatment PSA, postirradiation PSA fell in 416 of 424 men (98%). Prostate-specific antigen levels continued to fall for up to 12 months but there was no evidence of significant declines beyond that. The time to nadir PSA was: 3 months, 60 patients; 6 months, 68 patients, 9 months 148 patients; 12 months, 144 patients. Time to nadir was not a significant determinant of outcome. Prostate-specific antigen levels at 3 and 6 months and the nadir level were individually highly correlated with outcome. In multivariate analyses of posttreatment values, only the nadir value was independently significant, with increasing relapse rates as its value was higher. It retained significance when pretreatment PSA level was included in the model. Nadir values ranged from undetectable (52 patients) to 20.3 ng/ml with a median of 1.1 ng/ml. Nadir values down to 1 ng/ml were prognostic; below 1 ng/ml (182 patients) the nadir value no longer yielded prognostic information additional to that inherent in the pretreatment value. Only patients with nadir levels < 1 ng/ml fared well (5-year incidence of relapse or rising PSA 17%); however, if the pretreatment level exceeded 30 ng/ml, then even a nadir level < 1 ng/ml was associated with a 40% failure rate at 5 years. CONCLUSION: The nadir PSA value after radiation is a significant posttreatment determinant of outcome and was second only to the pretreatment value. Surprisingly low nadir values were prognostically significant. Only patients whose nadir falls below 1 ng/ml can be said to have achieved a biochemical complete remission. However, even such low nadir values do not portend durable disease control for patients with high pretreatment PSA levels.

Prostate specific antigen doubling time and disease relapse after radiotherapy for prostate cancer.

BACKGROUND: Serum prostate specific antigen (PSA) correlates with prostate tumor volume. Therefore, PSA-doubling time (PSA-DT) in patients with a rising PSA profile after radiotherapy should be predictive of the time to clinical disease relapse. The purpose of this study was to characterize the relationship between PSA-DT and the time to disease relapse after the onset of a rising PSA (PSA-TTR) in 427 men treated in the PSA-era with high dose radiotherapy for Stages T1-4 adenocarcinoma of the prostate. METHOD: There were 119 patients with a rising PSA profile after radiotherapy, and of these, there was sufficient information to calculate PSA-DT using nonlinear least squares regression in 100. There were 44 patients in this cohort who had documented disease relapse. The median patient follow-up was 38 months. RESULTS: The average PSA-DT was 13.5 plus or minus 11.6 mo (+/- standard deviation). PSA-DT values correlated with tumor grade, pretreatment PSA, and stage. PSA-DT was also strongly related to the outcome measures of local relapse, distant metastases, and any disease relapse. The shorter the PSA-DT, the greater the risk of disease relapse. The average PSA-TTR was 10.1 plus or minus 8.2. The only prognostic factor that correlated with PSA-TTR was tumor grade. A linear regression analysis of normalized PSA-DT and PSA-TTR revealed a significant correlation in which a PSA-DT of 11 months predicted for disease relapse 24 months later. Because several factors including physician and patient preferences could alter this relationship, a comparison was made between the actuarial PSA rise time for patients treated in the PSA-era and actuarial clinical disease relapse using a cohort of similarly treated men from the pre-PSA-era (n = 798). The results showed the lead time to be over 40 months in the majority of patients and that this lead time was much shorter in those with high grade tumors. CONCLUSIONS: PSA-DT is a strong prognostic factor for patients with biochemical evidence of failure after radiotherapy. A short PSA-DT predicts for more rapid progression to symptoms. The timing of the progression from a rising PSA to clinical disease relapse is probably longer than expected and is estimated to be 40 months on average.

FIGO stage IIIA carcinoma of the uterine cervix.

Between 1955 and 1988, 44 patients with FIGO Stage IIIA carcinoma of the cervix were treated with radiotherapy at The University of Texas M. D. Anderson Cancer Center. This represents only 3% of the 1473 Stage III cervical carcinoma patients treated at M. D. Anderson during this time period. The 5- and 10-year actuarial survival rates of patients with Stage IIIA disease were 37% and 34%, respectively. The actuarial pelvic disease control rate was 72% at 5 and 10 years. Of the 23 patients who experienced a recurrence of their disease, 10 had a recurrence in the pelvis only, 11 had distant metastases only, and two had recurrences in the pelvis and distantly. Two factors, parametrial disease extension and discontinuous involvement of the lower third of the vagina were important predictors of prognosis. The 5-year survival rate of 27 patients with parametrial involvement was 25% compared with 56% for the 17 patients without parametrial disease (p = 0.05). The 5-year survival rate of 13 patients with discontinuous ("skip") lesions in the lower third of the vagina was 15% compared with 48% for 31 patients who presented with direct extension of disease to the lower vagina (p = 0.05). This was because of a high rate of distant disease recurrence in patients with skip lesions since pelvic control rates were similar for both groups. No patient who presented with both parametrial extension and discontinuous vaginal involvement survived 5 years. In contrast, patients with lesions that extended directly from the cervix to involve the lower vagina without involving the parametrium had an excellent 5-year survival rate of 73%.