Postoperative radiation therapy for pathologic stage C prostate cancer

From 1971 to 1981, 26 patients with pathologic Stage C prostate cancer were referred to this department for postoperative radiation therapy. During the same period 24 patients, undergoing radical prostatectomy at this institution, were found to have pathologic Stage C disease but did not receive adjuvant irradiation. Both groups of patients are compared at 5 years post surgery for disease-free survival, local control, and distant failure in an attempt to determine whether there is a demonstrable benefit of adjuvant irradiation in this setting. All irradiated patients started therapy 1 to 4 months post surgery. All were treated with megavoltage irradiation. The majority were treated to the pelvis by a 4-field technique to an absorbed dose of 46-50 Gy followed by a prostate boost via multiple fields to a total dose of 54-70 Gy. Three patients received 50-52 Gy to the pelvis only and 5 patients received 56-65 Gy to localized prostate fields only. Moderate complications in the irradiated group were 23% with no severe complications observed. This rate may be reduced with treatment of local prostate fields only. There was no significant difference in 5-year survival, 5-year disease-free survival, or distant metastases in patients treated with surgery only or surgery plus radiation. However, local recurrence at 5 years was significantly different (p = 0.046), 16.6% in the surgery only group and 0 in the irradiated group. This difference was more pronounced in the subset of patients with seminal vesicle invasion: 30% local recurrence in the surgery only group versus 0 in the irradiated group. These data suggest that the addition of postoperative irradiation in pathologic Stage C prostate cancer yields an improvement in local control, and that for the subset of patients at significant risk of local relapse, those with seminal vesicle invasion, adjuvant prostate bed irradiation should be recommended.     

Long-term use of combined radiation therapy and hormonal therapy in the management of stage D1 prostate cancer

PURPOSE: To determine tumor response, patterns of relapse, and prognostic indicators in patients followed long-term after combined hormonal radiation therapy of adenocarcinoma of the prostate in men with tumor metastatic to pelvic lymph nodes. METHODS AND MATERIALS: Seventy-nine patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node metastases were treated with combined radiation therapy and hormonal therapy. Of these, 55 patients (70%) had T3 disease, with the remainder having earlier-stage disease; 45 (57%) patients had N2 disease (Whitmore-Jewett staging). No distant metastases were detected at initial staging, and no patient had radiographic or pathologic involvement of the para-aortic nodes. Pelvic lymph nodes were irradiated to a dose 45-54 Gy, and the prostate was irradiated to a dose 65-71.8 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose diethylstilbestrol (DES) (2 patients), orchiectomy (21 patients), luteinizing hormone-releasing hormone agonist (12 patients), or combined androgen blockade (44 patients). Prognostic factors examined included microscopic vs. measurable lymph node involvement, one-sided vs. two-sided disease, T stage, pretreatment PSA, method of androgen blockade, and Gleason score. Log-rank analysis was used to determine statistical significance with respect to overall survival, disease-free survival, clinical freedom from progression, and biochemical freedom from progression; Cox multivariate analysis was employed to determine potential confounders. RESULTS: Median follow-up was 6.7 years. There were 25 recurrences among the 79 patients, including 7 biochemical recurrences without clinical evidence of disease, three local recurrences in the prostate, and distant metastases in 14 patients; 2 patients were deceased, with cause of death listed as prostate cancer, though the location of recurrence was unknown. Patients with biochemical failure before 5 years were more likely to fail distantly, 16% vs. 4% (p < 0.001). Overall actuarial survival at 5, 8, and 12 years was 86%, 72%, and 53%, respectively, whereas actuarial disease-free survival was 90%, 87%, and 81%. Ten patients died of intercurrent disease; these included 4 patients who died of a separate (nonpelvic) malignancy of nonadenocarcinomatous histology with no elevation in PSA. When the potential prognostic variables were examined, a trend toward increased biochemical recurrence in patients with Gleason score >or=8 was observed; this became statistically significant when the 4 patients with known residual lymph node disease after biopsy were excluded (p < 0.03). Gleason score remained the only significant indicator on multivariate analysis. A single long-term toxic event, recto-ureteral fistula, was observed. CONCLUSION: Combined hormonal and radiation therapy continues to represent an effective treatment option for patients with adenocarcinoma of the prostate with metastasis confined to pelvic lymph nodes. All patient groups seem to have a better disease-free survival than that reported previously in single-modality hormone or radiation treatment series. There is a suggestion that patients with lower Gleason score have a lower risk for recurrence. Combined modality therapy may also extend disease-free survival and allow patients to maintain independent function.     

A prospective trial of postoperative vaginal radium/cesium for grade 1-2 less than 50% myometrial invasion and pelvic radiation therapy for grade 3 or deep myometrial invasion in surgical stage I endometrial adenocarcinoma

A prospective trial was performed to evaluate the recurrence rate and 5-year disease-free survival rate in patients with surgical Stage I endometrial adenocarcinoma. Patients with Stage I, Grade 1 or 2 disease, less than 50% myometrial invasion, and no evidence of disease outside the corpus of the uterus were treated by hysterectomy and bilateral salpingo-oophorectomy and postoperative vaginal radium/cesium (Group 1). Patients with surgical Stage I, Grade 3 disease or deep myometrial invasion, and histologically negative paraaortic lymph nodes were treated with postoperative pelvic radiation therapy (5000-5040 cGY) (Group 2). Patients with malignant peritoneal cytologic findings also received progesterone therapy. Of the 92 Group 1 patients, there have been no recurrences and the 5-year estimated disease-free survival rate was 99%. Of the 41 Group 2 patients, there have been four (9.7%) recurrences but only one (2.4%) within the treated field (pelvis), and the 5-year estimated disease-free survival rate was 88%. Of the 133 patients, the 5-year estimated disease-free survival rate was 96%, and only one patient (0.7%) had a local pelvic recurrence. Of the 16 patients with malignant peritoneal cytologic findings who were treated with progesterone therapy, none has had a recurrence.     

Impact of clinical, pathologic, and treatment-related factors on outcome in patients with locally advanced breast cancer treated with multimodality therapy

The authors reviewed the experience at their institution treating patients with locally advanced breast cancer using multimodality therapy to identify clinical, pathologic, and treatment-related factors affecting outcome. One hundred patients with locally advanced breast cancer were treated with definitive therapy at William Beaumont Hospital. Three patients had stage IIB disease, 45 patients had stage IIIA disease, and 52 patients had IIIB disease. Thirteen patients had inflammatory breast carcinoma. Seventy-four patients (74%) received trimodality therapy consisting of systemic therapy, radiation therapy, and surgery. Systemic therapy was delivered to 90 patients. Eighty-three patients (83%) received adjuvant radiation therapy. Eighty-five patients underwent mastectomy (85%). Multiple clinical, pathologic, and treatment-related factors were analyzed for their impact on outcome. The median follow-up was 47 months. Overall, the 5-year actuarial rates of local control, disease-free survival, overall survival, and cause-specific survival were 81%, 43%, 53%, and 55%, respectively. The 5-year actuarial cause-specific survival rates for patients with inflammatory breast carcinoma, stage IIIA disease, and stage IIIB disease were 25%, 55%, and 53%, respectively. On multivariate analysis, local control was improved with radiation therapy (p = 0.008) and the absence of inflammatory breast carcinoma (p = 0.008). Disease-free survival was improved with the addition of radiation therapy (p = 0.001) and with less than four positive lymph nodes (p = 0.003). Distant metastasis-free survival was improved in patients without inflammatory breast carcinoma (p = 0.0249) and with less than four involved lymph nodes (p = 0.0135). Cause-specific survival and overall survival were adversely affected by the presence of inflammatory breast carcinoma (p = 0.0135 and p = 0.0325, respectively) or four or more involved lymph nodes (p = 0.0082 and p = 0.012, respectively). Radiation therapy appears to be a critical component in the overall treatment of patients with locally advanced breast cancer by improving the rates of local control and disease-free survival. Other adverse factors for survival include four or more positive lymph nodes and inflammatory breast carcinoma.     

The effect of transurethral resection on prognosis in carcinoma of the prostate: real or imaginary?

From January 1970 to June 1983, a total of 702 patients received radical external beam radiation therapy for carcinoma of the prostate. The estimated 5- to 10-year disease-free survival are 67% and 52%. A comparison was made between those patients whose diagnosis was established by needle biopsy as compared with those who had a positive transurethral resection of the prostate (TURP). Within Stages B & C combined, the 5-year disease-free survival was 65% for needle biopsy as compared with 59% for TURP. The corresponding figures at 10 years are 50% and 43%. This difference is significant with a p-value of less than 0.01. In addition to histological grade, identifiable prognostic factors in the literature are clinical stage, serum acid phosphatase, and extent of radiation (local only or prophylactic pelvic nodal radiation). Assessment of histological grade using the Gleason method has been carried out in all except 7 cases. The amount of tissue from a needle biopsy constitutes less than 3% of the material obtained from a TURP. As a result, there is a potential sampling error. The Gleason grading can be used in at least three ways: (a) the conventional Gleason score, (b) the most malignant grade identified, or, (c) the primary (most frequent) grade identified. Analyzing use of these three methods of histological stratification yields conflicting results. The difference between the needle and TURP groups is present in late stage disease when the primary grade is used for stratification but absent when the worst grade is used. The significance of these results remains more or less constant irrespective of end point (uncorrected, disease specific or disease-free survival). However, when stratified by Gleason score, it is significant for disease specific survival, approaches significance for uncorrected survival but not for disease free survival. Since the significance can be altered by changing one stratification factor, there must be some doubt about the validity of other studies which either confirm or refute the hypothesis that TURP has an adverse influence on the disease process.     

Five-year biochemical outcome after prostate brachytherapy for hormone-naive men ≤ 62 years of age

To evaluate 5-year biochemical disease-free outcome for hormone naïve men 62 years of age or less who underwent transperineal ultrasound-guided permanent prostate brachytherapy.

76 patients underwent transperineal ultrasound guided prostate brachytherapy using either ¹⁰³Pd or ¹²⁵I for clinical T1b–T2b N×M0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up, and no patient underwent pathologic lymph-node staging. 47 patients were implanted with either ¹⁰³Pd or ¹²⁵I monotherapy, and 29 patients received moderate-dose external-beam radiation therapy followed by a prostate brachytherapy boost. No patient received hormonal manipulation. The median patient age was 58 years (range, 48–62 years). The median follow-up was 37 months (range, 14–70 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition.

The actuarial 5-year biochemical disease-free survival rate was 98.7%. For patients with low-, intermediate-, and high-risk disease, 97.7%, 100%, and 100%, respectively, were free of biochemical failure. The median posttreatment prostate-specific antigen (PSA) for the entire group was 0.2 ng/mL. When stratified by risk group, the median posttreatment PSA was 0.2, 0.15, and 0.1 for patients with low-, intermediate-, and high-risk disease, respectively.

With a median follow-up of 37 months, hormone naïve patients ≤ 62 years of age have a high probability of 5-year biochemical disease-free survival following permanent prostate brachytherapy with an apparent plateau on the PSA curve.     

Testicular seminoma. Results of the Yale University experience, 1964-1984

Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma.     

Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas.

From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.     

The incidence of metastases after multimodal therapy for cancer of the head and neck

Combined therapeutic regimens integrating chemotherapy, radiation therapy, and surgery are reported to be effective in treating advanced squamous cell carcinomas of the head and neck. The current study evaluates 58 consecutive patients with advanced (T4, N3) head and neck cancers. Forty patients (multimodal group) were treated with 2 courses of chemotherapy (cisplatin 2 mg/kg; methotrexate 280-560 mg/m2 with leucovorin rescue; bleomycin 30 mu X 3) followed by radiation therapy and surgery. Eighteen patients (combined group) were treated with preoperative radiation therapy followed by surgery. In the multimodal group there were 27 (67.5%) partial responses and nine (22.5%) complete responses, for an overall response rate of 90%. Response rates by site of primary lesion were: oral cavity, 11 of 11; oropharynx, 13 of 17; hypopharynx, 5 of 5; and larynx 7 of 7. Distant metastases (skin, lung, bone, central nervous system [CNS]) appeared in 16 patients (40%) (P less than 0.05 versus combined) at a median time of 8.5 months after diagnosis, 15 in patients having a partial (11) or complete (4) response. Thirteen patients (33%) developed distant metastases within 1 year of diagnosis (P less than 0.05 versus combined). In 11 of these patients, the primary lesion and neck disease were resectable. Two thoracotomies were performed for solitary pulmonary metastases; one was resected for cure. Fifteen patients (38%) underwent curative resection; 11 (73%) were alive at 1 year, and ten (67%) were free of disease. Overall survival was 20 of 40 (50%) at 1 year. In the combined group, there were 14 partial responses (78%) and no complete responses. Early distant metastases appeared in two patients (12.5%), at 2 and 6 months after diagnosis. Seven patients (38%) underwent curative resection; six of seven (86%) were alive at 1 year, four of seven (57%) were disease-free. Six of 16 patients at risk (37.5%) survived 1 year. After combined therapy, six of ten patients (60%) with responses to therapy survived 1 year versus 12 of 20 responders (57%) without distant metastases in the multimodal group. It is concluded that multimodal therapy for advanced head and neck cancer results in a higher response rate than with conventional combined therapy. The incidence of early and postoperative distant metastases was increased after the multimodal regimen. At 1 year there were no differences in survival between the combined and multimodal groups for responders without early metastases. Further observation is needed to determine the net long-term effects of this regimen. A prospective randomized comparison of combined and multimodal therapy for advanced lesions is indicated.     

Radiotherapy or surgery for prostate cancer? Ten and fifteen-year results of external beam therapy

Ten and 15-year outcome results are reviewed that demonstrate the role of radiation therapy in the management of prostate cancer. Patients with favorable T2a (B1) cancers of unknown nodal status are shown to have equal 15-year survival whether treated with external beam radiation therapy or radical prostatectomy. Patients of unknown nodal status treated for T2b (stage B2) cancer with external beam radiation therapy show superior survival and disease-free survival when compared to results with radical prostatectomy. The role of radical prostatectomy in these patients is unproven. Patients with lymph node dissection negative clinical stages T1b (A2) and T2 (B) treated with external beam radiation therapy exceed their expected survival at 10 years (65% vs 60%), and 70% are free of any failure at 10 years with the majority of failures due to metastasis, not local disease. Similar results are obtained in selected surgical centers with radical prostatectomy in highly selected patients. Patients with stage T3, 4 (stage C) prostate cancer show 10 and 15-year survivals that offer curative therapy and hope to patients with these locally advanced cancers. No long-term data support a role for radical prostatectomy in these patients.     

Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer: long-term results from Dana-Farber Cancer Institute study 94-153

BACKGROUND:

The authors present long‐term results from a phase 2 study that assessed the efficacy of transrectal ultrasound hyperthermia plus radiation with or without androgen suppression for the treatment of locally advanced prostate cancer.

METHODS:

Patients with clinical T2b‐T3bN0M0 disease (according to 1992 American Joint Committee on Cancer [AJCC] criteria) received radiation plus 2 transrectal ultrasound hyperthermia treatments. After the first 4 patients, 6 months of androgen suppression were allowed. The study was designed to assess absolute improvement in the 2‐year disease‐free survival rate compared with the short‐term androgen suppression arm in Radiation Therapy Oncology Group (RTOG) study 92‐02.

RESULTS:

Thirty‐seven patients received a total of 72 hyperthermia treatments. The mean cumulative equivalent minutes (CEM) T₉₀43°C was 8.4 minutes. According to the 1992 AJCC classification, there were 19 patients with T2b tumors, 8 patients with T2c tumors, 5 patients with T3a tumors, and 5 patients with T3b tumors. The median Gleason score was 7 (range, 6‐9), and the median prostate‐specific antigen (PSA) level was 13.3 ng/mL (range, 2‐65 ng/mL). Thirty‐three patients received androgen suppression. At a median follow‐up of 70 months (range, 18‐110 months), the 7‐year overall survival rate was 94%, and 61% of patients remained failure free (according to the American Society for Therapeutic Radiology and Oncology definition for failure free survival). The absolute rate of disease‐free survival at 2 years, which was the primary study endpoint, improved significantly (84%) compared with a rate of 64% for similar patients on the 4‐month androgen suppression arm of RTOG 92‐02. When Phoenix criteria (PSA nadir + 2 ng/mL) were used to define biochemical failure, 89% of patients were failure free at 2 years.

CONCLUSIONS:

Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer appeared to be promising. The current results indicated that further study of hyperthermia for the treatment of prostate cancer with optimal radiation and systemic therapy is warranted. Cancer 2010. © 2010 American Cancer Society.     

Five-year biochemical outcome following permanent interstitial brachytherapy for clinical T1-T3 prostate cancer

PURPOSE: To evaluate 5-year biochemical disease-free outcome for men with clinical T1b-T3a NxM0 1977 American Joint Committee on Cancer (1997 AJCC) adenocarcinoma of the prostate gland who underwent transperineal ultrasound-guided permanent prostate brachytherapy. METHODS AND MATERIALS: Four hundred twenty-five patients underwent transperineal ultrasound-guided prostate brachytherapy using either 103Pd or 125I, for clinical T1b-T3a NxM0 (1997 AJCC) adenocarcinoma of the prostate gland, from April 1995 to October 1999. No patient underwent pathologic lymph-node staging. One hundred ninety patients were implanted with either 103Pd or 125I monotherapy; 235 patients received moderate-dose external beam radiation therapy (EBRT), followed by a prostate brachytherapy boost; 163 patients received neoadjuvant hormonal manipulation, in conjunction with either 103Pd or 125I monotherapy (77 patients) or in conjunction with moderate-dose EBRT and a prostate brachytherapy boost (86 patients). The median patient age was 68.0 years (range, 48.2-81.3 years). The median follow-up was 31 months (range, 11-69 months). Follow-up was calculated from the day of implantation. No patient was lost to follow-up. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. RESULTS: For the entire cohort, the 5-year actuarial biochemical no evidence of disease (bNED) survival rate was 94%. For patients with low-, intermediate-, and high-risk disease, the 5-year biochemical disease-free rates were 97.1%, 97.5%, and 84.4%, respectively. For hormone-naive patients, 95.7%, 96.4%, and 79.9% of patients with low-, intermediate-, and high-risk disease were free of biochemical failure. Clinical and treatment parameters predictive of biochemical outcome included: clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, risk group, age > 65 years, and neoadjuvant hormonal therapy. Isotope choice was not a statistically significant predictor of disease-free survival for any risk group. The median postimplant PSA was < or = 0.2 for all risk groups, regardless of hormonal status. The mean posttreatment PSA, however, was significantly lower for men implanted with 103Pd (0.14 ng/mL) than for those implanted with 125I (0.25 ng/mL), p < or = 0.001. CONCLUSION: With a median follow-up of 31 months, permanent prostate brachytherapy results in a high probability of actuarial 5-year biochemical disease-free survival (DFS) for patients with clinical T1b-T3a (1997 AJCC) adenocarcinoma of the prostate gland, with an apparent plateau on the PSA survival curve.     

High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.     

Three-dimensional conformal therapy versus standard radiation therapy in localized carcinoma of prostate: an update

This study updates technical principles and results of 3-dimensional conformal radiation therapy (3D-CRT) in localized carcinoma of the prostate. Between January 1992 and December 1999, 312 patients were treated with 3D-CRT and 135 patients were treated with bilateral arcs standard radiation therapy (SRT) alone for clinical stage T1b-c or T2 histologically confirmed prostate cancer. None of these patients received hormonal therapy. Mean follow-up for patients in the 3D-CRT group was 3.2 years (range, 2-5.9 years) and for SRT patients, 4.7 years (range, 4-7 years). For 3D-CRT, 7 intersecting fields were used (cerrobend blocking or multileaf collimation) to deliver 68-74 Gy to the prostate. Standard radiation therapy consisted of bilateral 120 degree rotational arcs, with portals using 2-cm margins around the prostate to deliver 68-70 Gy to the prostate. The criterion for chemical disease-free survival was a postirradiation prostate-specific antigen (PSA) value following the American Society for Therapeutic Radiology and Oncology guidelines. Symptoms during treatment were quantitated weekly, and late effects were assessed every 4-6 months. Dose-volume histograms showed a two-thirds reduction with 3D-CRT in normal bladder or rectum receiving > or = 70 Gy with 3D-CRT. Higher 5-year chemical disease-free survival was observed with 3D-CRT (75%; for T1b-c and 79%; for T2 tumors) compared with SRT (61% and 65%, P = 0.01 and P = 0.12, respectively). There was no statistically significant difference in chemical disease-free survival in patients with Gleason score of < or = 4 (P = 0.85), but, with Gleason score of 5-7, the 5-year survival rates were 83% with 3D-CRT and 59% with SRT (P < or = 0.01). In 245 patients with pretreatment PSA of < or = 10 ng/mL treated with 3D-CRT, the chemical disease-free rate was 80% versus 72% in 98 patients treated with SRT (P = 0.21). In patients with PSA of 10.1-20 ng/mL, the chemical disease-free survival rate for 50 patients treated with 3D-CRT was 71% compared with 43% for 20 patients treated with SRT (P = 0.02). The corresponding values were 59% and 16%, respectively, for patients with PSA levels > 20 ng/mL (P = 0.09). On multivariate analysis, the most important prognostic factors for chemical failure were pretreatment PSA (P = 0.004), nadir PSA (P = 0.001), and 3D-CRT technique (P = 0.012). Moderate dysuria was reported by 2%-5% of patients treated with 3D-CRT in contrast to 6%-9% of patients treated with SRT. The incidence of moderate loose stools or diarrhea, usually after the fourth week of treatment, was 3%-5% in the 3D-CRT patients and 8%-19% in the SRT group. Late intestinal grade 2 morbidity (proctitis or rectal bleeding) was 1% in the 3D-CRT group in contrast to 7% in SRT patients. The 3D-CRT spares more normal tissues, yields higher chemical disease-free survival, and results in less treatment morbidity than SRT in treatment of stage T1-T2 prostate cancer. Follow-up at > or = 10 years is needed to confirm these observations.     

Limb salvage in soft tissue sarcomas involving neurovascular structures using combined surgical resection and brachytherapy

While there is debate in the literature concerning the tolerance of neurovascular structures to external beam radiation, the tolerance of these tissues to interstitial radiation has never been established. To evaluate the dose of radiation and its effect on early and late toxicity of neurovascular structures, a retrospective review of our experience was undertaken. Between 1975 and 1987, 299 patients with extremity sarcomas underwent limb-sparing surgery and tumor bed Iridium-192 interstitial implantation at Memorial Sloan-Kettering Cancer Center. Forty-five patients (15%) of this group were found to have locally advanced tumors involving major neurovascular structures. Of these patients, 64% had high grade lesions. Eleven percent had evidence of gross residual disease on these structures, and an additional 58% had microscopic residual disease at or close to the margins of resection. After loading catheters were placed directly upon the neurovascular structures in the exposed tumor bed and a median dose of 4400 cGy was delivered to the target volume. Eight patients had previous radiation to the treated field and 13 patients received postoperative radiation. With a median follow-up of 4 years, the 5-year actuarial disease-free survival was 69% and the 5-year actuarial freedom from in-field failure was 79%. The 5-year actuarial incidence of distant metastases was 30%. Eighty-four percent of the patients maintained long-term preservation of limb function without the need for amputation. Four patients (9%) ultimately developed evidence of radiation neuritis 6-20 months post therapy. All four patients had received additional radiation with cumulative doses exceeding 9000 cGy to the neurovascular bundle. We conclude that combined surgical resection and interstitial radiation for locally advanced sarcomas with neurovascular involvement can provide excellent local control with preservation of limb and neurovascular function without significant toxicity.     

Prognostic significance of pelvic recurrence and distant metastasis in prostate carcinoma following definitive radiotherapy.

This report is a retrospective analysis of 317 patients with recurrent prostate carcinoma, following definitive radiation therapy to 738 patients with histologically confirmed, clinical Stage T1b-T4(A2-D1) adenocarcinoma of the prostate. Seventy-four patients (10%) experienced pelvic recurrence only; 100 (13%) both pelvic recurrence and distant metastasis, while 143 (20%) developed distant metastasis only. The diagnosis of prostate recurrence was histologically confirmed in 92/174 (53%), while in the others diagnosis was based on clinical and radiographic evidence. Ninety percent of all recurrences occurred within 7 years of initial treatment. The median survival from time of recurrence for all patients was 27 months, with 5-, 8-, and 10-year survival rates of 24%, 12%, and 7%, respectively. In patients who experienced pelvic recurrence only, the 5-, 8-, and 10-year survival rates were 50%, 30%, and 22%, respectively (p < 0.0001). The 5-year survival rate from time of recurrence for patients who experienced pelvic recurrence with initial Stage T1b(A2) and T2(B) disease was 71% as opposed to 39% for patients with initial Stage T3(C) disease. The time of recurrence (i.e., the disease-free interval from initial treatment) significantly affected subsequent survival: the 5-year survival rates from time of recurrence for patients with pelvic recurrence were 20%, 49%, and 94% for those who recurred within 2 years, 2 to 5 years, and more than 5 years, respectively. Two-thirds of the patients with recurrence received hormonal therapy, including bilateral orchiectomy. Salvage therapy with hormones, including bilateral orchiectomy, has a favorable impact on patient survival: The 5-year survival rate from time of pelvic recurrence salvaged with hormones was 70% compared with 21% for patients not receiving hormonal therapy. In conclusion, the prognostic factors that affect subsequent patient survival after pelvic recurrence include initial stage, disease-free interval from initial treatment, and salvage therapy with hormones. Patients with distant metastasis with or without pelvic recurrence showed statistically worse survival and were apparently not influenced by initial tumor stage, or disease-free interval from initial treatment.     

中晚期前列腺癌同期调强放疗联合内分泌治疗的临床观察

目的 观察中晚期前列腺癌同步三维适形调强放疗联合内分泌治疗的疗效及不良反应。方法 67例中晚期前列腺癌患者接受同步三维适形调强放疗联合内分泌治疗：2.2～2.4Gy/f,每天1次,每周5次,共31次,DT 70～75Gy;放疗第1天起口服氟他胺0.25g/次,每天3次。评价疗效及不良反应,并分析影响放射性直肠损伤的因素。结果 67例患者均完成治疗,获CR 21例、PR 37例、SD 9例,总有效率（RR）为86.5%。随访时间为12.5～99.6个月,6例失访。随访满5年者（包括随访5年内死亡患者）共39例,其3、5年生存率分别为89.0%、80.5%,3、5年无进展生存率为72.0%、63.0%。肿瘤GTV≥141cm³者的中位生存时间为36.7个月,较GTV＜141cm³者的56.9个月短,差异具有统计学意义（P=0.037）。全组患者白细胞减少和血红蛋白减少的发生率分别为91.0%、89.6%,急性肝损伤为3.0%,急性放射性肠炎和放射性膀胱炎分别为100.0%和95.5%。肿瘤GTV体积是影响放射性直肠损伤的因素（P＜0.05）。结论 同步适形调强放疗联合内分泌治疗治疗中晚期前列腺癌患者的有效率高,不良反应可耐受,预后良好。     

Recent advances in the treatment of prostate cancer

As new evidence for prostate cancer treatment has emerged in the last few years, longstanding controversies in the treatment of prostate cancer have resurfaced. A number of long-held tenets of prostate cancer therapy have been revisited, sometimes with surprising and challenging results. Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer. Palliative benefit of chemotherapy for hormone refractory prostate cancer remains an important endpoint; survival advantage has not been seen in any randomized trials. Suramin may delay disease progression in hormone refractory prostate cancer. Many aspects of prostate cancer treatment will remain controversial until results of large, randomized trials with longer follow-up are available.     

A comparison of preoperative radiotherapy regimens for bladder carcinoma. The University of Pennsylvania experience

Between 1976 and 1985, 155 patients from the Hospital of the University of Pennsylvania, the Philadelphia Veterans Administration Hospital, and the Fox Chase Cancer Center were divided into groups, each of which was treated with one of three preoperative radiotherapy regimens to be followed by cystectomy. Patients initially were treated with 4000 cGy during 4 weeks followed by cystectomy (16 patients). Beginning in 1978, patients received 2000 cGy in 1 week prior to surgery (70 patients). Since 1982, 40 patients were treated with 500 cGy on the day prior to surgery with postoperative radiation therapy reserved for patients with either involved margins of resection, advanced stage or high grade. A fourth group of 20 patients was either not offered or refused preoperative radiation. Nine patients received only postoperative radiation therapy. The 5-year actuarial disease-free survival for pathologic Stages B2, C, and D lesions (T3-4, N0-2), was 63% for those who had received high-dose radiation versus 21% for those that had low-dose or no radiation. Patients with advanced pathologic stage disease who had received greater than 2000 cGy had a reduced rate of local failure (11% versus 27% for those who had received less treatment). Patients with abnormal upper tracts as shown on the intravenous pyelograms (IVP) had a reduced 5-year determinate survival of 23% versus 65% for patients with normal upper tracts. This condition did not independently affect survival, but rather reflected advanced stage. Patients with abnormal creatinine levels had a decreased survival that was independent of stage. Computed tomography was found to have low sensitivity for determining extravesical extension (39%) and metastatic lymphadenopathy (12%). Patients with clinical Stage B2 and C disease (T3) that were downstaged had a 63% 5-year survival versus 18% of those that were not downstaged. The incidence of both ureteroenteral strictures and stomal complications was found to be higher in the 2000 cGy group than in those patients treated with the other regimens. The overall incidence of complications in that group was also significantly greater. We conclude that there is a continuing role for adjuvant radiotherapy in invasive bladder carcinoma to improve both pelvic control and survival. The 500 cGy radiotherapy "sandwich" regimen was equal in terms of pelvic control and survival to the other regimens and showed less overall morbidity. The 2000 cGy regimen was associated with the greatest incidence of morbidity and did not substantially improve pelvic control.     

Radiotherapy following radical prostatectomy in patients with adenocarcinoma of the prostate

From 1973 to 1986, 160 patients with adenocarcinoma localized to the prostate were treated with radical prostatectomy and pelvic lymphadenectomy. In 78 (49%) patients more advanced stage of disease was found at surgery and they received local pelvic irradiation (RT). This consisted of 45 Gy for microscopic and 55 Gy for macroscopic residual disease. RT was given at 1.8 Gy a day, using the four-field "box" technique with the 23 MV X ray beam. Pelvic lymph node metastases were found in 28 (36%) patients who, in addition to RT, received systemic therapy: 20 with cyclophosphamide alone, 4 combined with 5-Fluorouracil, and 4 patients received DES. The 5- and 10-year overall actuarial survival was 95 and 77%, respectively, and the 5- and 10-year disease-free survival was 58 and 43%, respectively. Recurrent tumor was found in 34 (44%) patients. Of these 34 patients, 32 (94%) had distant metastatic tumor and 2 (6%) had local recurrence in the pelvis. The presence of metastatic disease in pelvic lymph nodes had clinical significance since it influenced disease-free survival and the incidence of tumor recurrence. The 10-year disease-free survival for the 50 patients with no lymph node metastases was 51%, as compared to 28% for the 28 patients with such metastases, p = 0.001. Similarly, recurrent tumor was found in 28% of the former and 68% of the latter patients, p = 0.002. Other important parameters predicting recurrence were: clinical stage, p = 0.018, histological grade, p = 0.013, and Gleason's grade, p = 0.002. This treatment program was very well tolerated and of low toxicity. There was no surgical mortality. Surgical complications were seen in 10 (13%) patients including: minor in 5 and major in 5. At 1 year, 77% of the patients remained continent, while 10% had mild stress incontinence. Of the remaining 13% only 3 (4%) patients had severe incontinence (greater than 5 pads daily). RT toxicity was mild with 38% experiencing diarrhea. Severe toxicity was seen in 2 (3%) patients who, early in the study, developed scrotal and lower extremity edema. Severe chemotherapy complications were seen in 1 (4%) patient who had severe neutropenic sepsis. Postoperative radiotherapy is a well tolerated, safe and effective treatment in patients who have microscopic or macroscopic residual tumor following radical prostatectomy.