Cisplatin, cyclophosphamide and doxorubicin chemotherapy for unresectable urothelial tumors: the M.D. Anderson experience

We reviewed retrospectively 97 patients treated with cisplatin, cyclophosphamide and doxorubicin chemotherapy at our hospital to evaluate predictive variables for response to chemotherapy and long-term survival free of disease. Histological subtype influenced response: 70 per cent of the patients with pure transitional cell carcinoma achieved an objective response (partial remission 31 per cent and complete remission 39 per cent), whereas 45 per cent of those with mixed tumors achieved response (partial remission 20 per cent and complete remission 25 per cent). Patients with nodal metastases only had an equal over-all response rate to those with visceral metastasis (64 versus 62 per cent) but patients with nodal metastases had a higher complete remission rate (45 versus 20 per cent). A total of 35 patients (36 per cent) achieved a complete response. In 17 of the 35 patients the duration of response was less than 100 weeks and 18 (51 per cent) have survived longer than 100 weeks. Of the 17 patients with a survival free of disease of less than 100 weeks 16 died of recurrent urothelial tumors and 1 died of a second primary tumor. Among the patients with a survival free of disease of longer than 100 weeks only 2 have had recurrent urothelial tumors; 72 per cent of the patients in this category remain free of disease. Patients with pure transitional cell carcinoma were represented in equal frequency among patients achieving a durable complete remission and those with a complete remission of less than 100 weeks. These data demonstrate the ability of cisplatin, cyclophosphamide and doxorubicin combination chemotherapy to achieve a complete remission and long-term survival free of disease among select patients with unresectable urothelial tumors.     

Validation of the tumor, nodes and metastasis classification of renal cell carcinoma

A retrospective analysis of 252 patients with renal cell carcinoma was performed with the tumor, nodes and metastasis system of cancer staging. Each patient received a clinical and a pathological classification. Patient survival was calculated for each pT stage. All patients with stage pT1 disease (100 per cent) were alive at 5 years, as were 91 per cent of those with stage pT2 tumors. Higher T stages showed poorer survival; 58 per cent of the patients with stage pT3 and only 25 per cent with stage pT4 tumors were alive at 5 years. Invasion into the inferior vena cava (pT3c) had an adverse effect on survival, which was statistically significant compared to patients in the pT3a and pT3b subgroups. The type of surgical procedure performed had no influence on ultimate survival, nor did the use of adjuvant radiation therapy. The tumor, nodes and metastasis system clearly documents that the survival of patients with renal cell carcinoma depends on the local extent of the primary tumor, determined at the time of surgical exploration.     

Stage T1, grade 3 transitional cell carcinoma of the bladder: an unfavorable tumor?

Transurethral resection only was performed in 172 patients with initial stage Ta, T1 transitional cell carcinoma of the bladder. Additional treatment during the course of disease was given to 9 patients with carcinoma in situ and to 8 patients with tumor progression. The mean followup was 106 months. The 10-year survival rates were 95 per cent for patients with stage Ta, grade 1 disease, 89 per cent for stage Ta, grade 2, 84 per cent for stage Ta, grade 3, 78 per cent for stage T1, grade 2 and 50 per cent for stage T1, grade 3. The percentage of first tumor recurrence at the same site increased with tumor grade (stage T1, grade 3 was 74 per cent). The recurrence rate in stage T1, grade 3 tumors (4.08) differed significantly from the other groups of superficial tumors. The tumor progression rate for stage T1, grade 3 tumors (32.5 per cent) was significantly higher as well. The characteristics of stage T1, grade 3 tumors with and without progression were different in regard to multiplicity, recurrence rate, mean interval to recurrence and type of tumor invasion. Of the 13 patients who died of progressive neoplastic disease 11 presented initially with stage T1, grade 3 tumors. When these results are considered it is obvious that a patient with a stage T1, grade 3 tumor deserves additional therapy, such as chemotherapy, immunotherapy or phototherapy.     

Well differentiated clear cell renal carcinoma: significance of nuclear deoxyribonucleic acid patterns studied by flow cytometry

Nuclear deoxyribonucleic acid ploidy was determined in 206 samples of well differentiated clear cell renal carcinoma via a previously described technique on paraffin-embedded archival material. Grade 2 tumors had a higher incidence of abnormal deoxyribonucleic acid patterns than grade 1 tumors. Of stage 1 well differentiated clear cell renal tumors 60 per cent had a normal deoxyribonucleic acid histogram pattern, whereas 67 per cent of higher stage tumors had an abnormal pattern. The existence of abnormal nuclear deoxyribonucleic acid histogram patterns in the primary tumor tissue had a significant correlation with subsequent development of metastatic disease, independent of tumor grade and stage. The 10-year actuarial survival rate was 62 per cent for patients with normal deoxyribonucleic acid histograms and 37 per cent for patients with abnormal patterns. These results demonstrate that nuclear deoxyribonucleic acid ploidy measured by flow cytometry is an important variable in the classification and determination of prognosis for patients with clear cell renal carcinoma.     

Radical prostatectomy for stage D1 prostate cancer. Prognostic variables and results of treatment

Surgical extirpation of the primary tumor together with the involved regional nodes has been considered ineffective treatment for locally disseminated prostatic carcinoma. We retrospectively reviewed our experience with 42 patients with Stage D1 disease who underwent radical prostatectomy and bilateral pelvic lymphadenectomy and who had a follow-up of one to thirteen years (mean 5 years). The following variables affecting survival and tumor progression were analyzed: (1) tumor grade and local extent; (2) number of positive lymph nodes, and (3) adjuvant therapy. The overall five- and ten-year survival was 79.5 per cent and 28 per cent compared with the expected survival of an age-matched control group of 88 per cent and 28 per cent, respectively. The degree of tumor differentiation had no effect on prognosis, but local tumor bulk and the number of involved lymph nodes significantly changed the disease progression and survival rate. Patients with low local tumor bulk and one positive node survived as long as the age-matched male population group. Our data suggest that radical prostatectomy may represent a valuable treatment in selected patients with Stage D1 prostate carcinoma.     

Renal pelvic carcinoma: morphological correlates of metastatic behavior

We report a clinicopathological analysis of morphological parameters in relation to subsequent biological behavior in 48 patients with renal pelvic carcinoma. The relationships of subsequent metastasis to tumor stage and grade, as well as the presence of vascular, renal parenchymal or renal hilar invasion were evaluated by parametric and nonparametric statistical tests. Corrected 5-year survival rates for grades 1 to 3 tumors were 100, 67 and 5 per cent, respectively. Grade 3 tumors demonstrated more invasion of the blood vessels, hilus and renal parenchyma compared to grades 1 and 2 tumors (p less than 0.005, 46 patients). Moreover, invasion of renal hilar tissues had greater predictive value for subsequent distant metastatic spread (95 per cent, nonparametric) than either vascular (83 per cent) or renal parenchymal (77 per cent) invasion. Metastases developed in 27 of 48 patients during followup periods of 2 to 39 years. The pattern of metastatic lesions revealed that local spread to hilar soft tissues occurred in 92 per cent of the patients who subsequently had distant metastases. Spread to retroperitoneal lymph nodes and ipsilateral ureteral mucosa occurred in 84 and 44 per cent of the patients, respectively. Our study illustrates the potential value of analysis of individual histological parameters to evaluate the likelihood of subsequent metastasis.     

Regional lymphadenectomy for renal pelvic and ureteral cancers

Thirty-four patients with renal pelvic and ureteral cancers received regional lymphadenectomy since 1980. The patients consisted of 21 with renal pelvic cancers, 10 with ureteral and 3 with renal pelvic and ipsilateral ureteral. Fifteen patients (44.1%) had metastatic nodes: 13 with renal hilar or para-aortic metastases and 2 with pelvic nodal involvements only. Thirteen of these 15 patients with nodal metastasis had high grade tumors and 14 had high stage tumors. The 5-year survival rate of these 15 patients was 26.3% which was considerably poor when compared with 19 patients without metastasis. Twenty patients with high grade and high stage tumors who received respective operations with regional lymphadenectomy had significantly better prognosis compared with the historical control group (15 patients, from 1961 to 1979). Additional regional lymphadenectomy for renal pelvic and ureteral cancers appears to be a valuable operation for improving prognosis.     

Pelvic lymphadenectomy for staging prostatic carcinoma: is it always necessary?

There were 100 patients with clinically localized prostatic carcinoma staged surgically for the evaluation of lymph node metastases. By correlating the incidence of lymph node metastasis with the level of serum acid phosphatase, and the stage and grade of the primary tumor, it was possible to identify 1 group of patients with less than 8 per cent incidence of lymph node metastases and another group with more than 92 per cent incidence of nodal involvement. It is in these 2 groups of patients that pelvic lymphadenectomy for the staging of prostatic carcinoma may not be necessary.     

Metaplastic breast cancer: clinical features and outcomes

Metaplastic carcinoma of the breast, a neoplasm with both epithelial and mesenchymal elements, represents less than 1 per cent of all breast cancer. We reviewed the records of all patients diagnosed with localized metaplastic breast cancer from 1991 to 2003 at our institution. We identified 21 patients. Mean primary tumor size was 4.62 cm. Eight patients (38%) had axillary node involvement at presentation. All the tumors were high grade. Only two (10%) of the tumors were hormone receptor positive. Seventeen (81%) of the patients received adjuvant chemotherapy, and 12 (57%) of the patients received radiation. Ten (29%) patients suffered a local recurrence. With a mean follow-up of 46 months, the 5-year disease-free and overall survival was 42 per cent (95% CI: 20% to 65%) and 71 per cent (95% CI: 46% to 96%), respectively. Stage-specific overall survival was 100 per cent, 83 per cent, and 53 per cent for stages I, II, and III, respectively. By multivariate analysis, there was no impact on recurrence or survival with regard to size, age, menopausal status, nodal status, histologic subtype, adjuvant therapy, or extent of surgery. Metaplastic breast cancer is a unique neoplasm that tends to present at an advanced stage and has a propensity for local recurrence. When stratified by stage, however, survival appears similar to that of adenocarcinoma of the breast, and these tumors should be treated as such.     

Treatment of stage I and II oral tongue cancer

We reviewed 156 previously untreated patients with squamous cell carcinoma of the oral tongue staged T1 and T2 to determine the incidence of nodal metastasis, and if elective neck dissection affected local/regional control or survival. Patients were divided into two nonrandomized groups: group 1, intraoral glossectomy only (102 patients); and group 2, intraoral glossectomy plus neck dissection (54 patients). Analysis revealed no significant differences for tumor location, histologic differentiation, status of margins, or clinical appearance; however, perineural invasion significantly adversely affected survival and local/regional control. In group 1 patients, 16.5% subsequently developed cervical metastasis, and 20.4% of patients in group 2 had occult nodal disease. The survival and local/regional control for group 1 patients subsequently developing nodes was 33% and 50%, respectively. The survival and local/regional control for group 2 patients with occult metastasis was 55% and 91%, respectively. We believe elective neck dissection is indicated for early staged oral tongue cancer.     

Results of radical cystectomy for primary bladder cancer. Retrospective study of more than 200 cases

During a seven-year period 202 patients with primary bladder cancer had radical cystectomy with bilateral pelvic lymphadenectomy and urinary diversion. Lymph node metastases were found in 28.7 per cent. No significant differences in overall survival owing to age were apparent. Only extension and grade of histopathologic differentiation of the tumor proved to be an important prognostic factor. The five-year survival rates for pT1, pT2, pT3, and pT4 tumors were 76, 56, 19, and 0 per cent, respectively. In patients with deep invasive (T3 and T4) tumors no significant differences of survival rate depending on N and M categories were found. Nevertheless in pT3 tumors the probability of remaining alive was significantly decreased in those patients with histologic grade 3 compared with grade 2 tumors (P less than 0.01). The prognosis for patients submitted to radical cystectomy for bladder cancer has been classified as good: tumors confined to superficial muscle (pT1 and pT2); intermediate: tumors mildly differentiated infiltrating the deep muscle (pT3/G2); fairly poor: tumors undifferentiated infiltrating deep muscle (pT3/G3); and poor: adjacent invasive bladder tumors (pT4).     

Invasive bladder cancer: tumor configuration, lymphatic invasion and survival

The pathologic slides of 86 patients who underwent radical cystectomy for invasive (stage T2 plus) bladder carcinoma were reviewed. The tumors were classified according to the demonstration or absence of small vessel invasion and the papillary or solid configuration. Of the 86 patients regional nodal metastases were noted in 24. Eighteen of 48 patients (38 per cent) with small vessel invasion also had nodal metastases compared to 6 of 38 (16 per cent) without small vessel invasion. Of the 62 patients without nodal metastases the crude 5-year survival was 52 per cent for 32 without small vessel involvement compared to 30 per cent for 30 with small vessel involvement.     

Penile cancer: relation of extent of nodal metastasis to survival

A retrospective review of 199 patients with penile cancer revealed that the extent of inguinal nodal metastasis was related to survival after radical ilioinguinal dissection. Patients with unilateral inguinal nodal involvement had a 56 per cent median 5-year survival rate, whereas those with bilateral inguinal nodal metastasis, extranodal tumor extension or iliac nodal involvement had a 9 per cent median 5-year survival rate.     

Histopathological Determinants of Survival in Resected Cases of Pancreas Cancer

We have examined the histopathological factors affecting the degree of local spread, regional lymph node (RLN) metastases, and overall survival (O.S.) in a group of 39 cases of resected carcinoma of the exocrine pancreas. Although the mean O.S. for the group was 14.3 months, resected patients without RLN involvement had a mean survival of 24 months. In contrast the mean O.S. rate was 8 months for patients with RLNs involved. Size, tumor location, and histological grade were compared to RLN involvement and O.S. The mean size of primary tumor did not differ significantly between patients with or without RLN''s (r.1 versus 4.6cms). However, 7 or 8 T₁ tumors were <4cm and 35% of tumors <4cm were T₁ lesions. In contrast, only of 17 tumors (6%) >4cm was T₁. Histological grade was correlated with nodal status and O.S. There was a significant difference between histological grade and the presence of metastatic lymph nodes (G1, 37% positive, G2-4.50% positive). Patients with well differentiated tumors had a mean survival of 21 months compared to a mean survival of 10 months for less differentiated tumors (p<0.05). This difference was even more significant when stratified for nodal status. The patients with well differentiated tumors and no RLN involvement had a mean survival of 32.5 months compared to 8.6 months for well differentiated tumors with RLN involvement. In summary, we have shown that size, histological grade, and local spread predict for nodal status. However, specific patient subsets (G1, node negative) may exhibit an excellent survival when curative pancreas resection is successful.     

Full-dose irradiation for patients with invasive bladder carcinoma: clinical and histological factors prognostic of improved survival

We reviewed the outcome of 55 patients treated from 1974 to 1982 by full-dose radiation therapy (6,400 to 6,800 rad) to identify factors associated with tumor radioresponsiveness and patient cure. All patients had histological proof of muscle invasion by tumor. Of the patients 8 (14 per cent) had clinical stage T2, 29 (53 per cent) stage T3 and 18 (33 per cent) stage T4 disease. Thirteen patients are alive, all but 2 without evidence of cancer. Survivors include 1 of 9 patients who underwent salvage cystectomy for a local recurrence. The actuarial 5-year survival rate for the entire group was 28 per cent, with a corrected survival of 33 per cent. Median survival was 2.3 years. Corrected survival for patients with stages T2 and T3 disease was 45 per cent versus 9 per cent for those with stage T4 cancer (p equals 0.009). Within the group with stages T2 and T3 cancer (all with proof of muscle invasion) the most striking prognostic factor was papillary surface histological findings, with local control by radiation therapy alone of 63 per cent versus 20 per cent in the group with solid or flat tumors (p equals 0.01), and corrected 5-year survival of 62 per cent (papillary) versus 0 per cent (flat or solid) (p equals 0.002). Other significant prognostic factors for 5-year survival in this group were extent of transurethral resection (54 per cent complete versus 17 per cent incomplete, p equals 0.009) and ureteral obstruction on excretory urography (47 per cent without versus 14 per cent with, p equals 0.01). Our results suggest that full-dose radiation therapy can be offered to patients with muscle-invading bladder cancer, with a relatively higher probability of success in those with less advanced tumors by clinical stage, papillary surface histological findings and no ureteral obstruction, and in whom a complete transurethral resection is possible.     

Prognostic factors in localized prostatic carcinoma

Serial histological sections were performed in 54 radical prostatectomy specimens in an attempt to identify prognostic factors responsible for dissemination of prostatic cancer. Factors considered in the study included clinical versus pathological staging, histological grading of the biopsy specimen compared to the final pathological result, intraprostatic tumor distribution and deoxyribonucleic acid analysis of the tumor by flow cytometry in the last 33 cases. In patients with clinical stages A2 and B1 disease pathological findings were in accord in 78 per cent (11 of 14). However, only 3 of 40 patients with clinical stage B2 tumor had pathological stage B2 disease. Histologically, 72 per cent of the tumors were bilateral. Microscopic involvement of the capsule per se did not appear to influence lymph node invasion, since only 1 of 27 patients with microscopic capsular involvement had pelvic lymph node metastasis. However, 9 of 13 patients with seminal vesicle involvement had pelvic lymph node metastasis. The addition of flow cytometry to the Gleason score improves the predictive value of histological grade in higher stage lesions.     

Effect of local tumor control on distant metastasis and survival in prostatic adenocarcinoma

Of 495 patients definitively irradiated for prostatic carcinoma, 286 with a minimum follow-up of thirty-six months were studied. While tumor histology appeared to predict prognosis, the poorly differentiated tumors showing the highest incidence of distant metastasis and the lowest survival, local tumor control was an important factor within the poorly differentiated group. Of those with local recurrence, distant metastases developed in 68 per cent compared with 37 per cent of those with no local disease (p = 0.025). Survival was similarly affected with 86 per cent of those with locally controlled tumor who were alive at five years (not significantly different from the more well-differentiated tumors) versus a 56 per cent actuarial survival in those with locally recurrent disease (p less than 0.05).     

Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage,thickness, shape,growth pattern,invasive front malignancy grading,Martinez-Gimeno score,and pathologic features

PURPOSE: This study aims at evaluation of the different prognostic models, including stage, tumor thickness, shape, malignancy grading of tumor invasive front, Martinez-Gimeno score, and pathologic features in the prediction of subclinical nodal metastasis, local recurrence, and survival of early T1 and T2 oral tongue squamous cell carcinoma. The results will have important implication for the management of patients. PATIENTS AND METHODS: Seventy-two clinically T1 and T2 glossectomy specimens of oral tongue carcinoma were serially sectioned in 3-mm thickness for the evaluation of various pathologic features. The prognostic value in the prediction of subclinical nodal metastasis, local recurrence, and survival of different models were compared. RESULTS: Among all the tumor parameters and predictive models being evaluated, tumor thickness was the only significant factor that had significant predictive value for subclinical nodal metastasis, local recurrence, and survival. With the use of 3-mm and 9-mm division, tumor of up to 3-mm thickness has 8% subclinical nodal metastasis, 0% local recurrence, and 100% 5-year actuarial disease-free survival; tumor thickness of more than 3 mm and up to 9 mm had 44% subclinical nodal metastasis, 7% local recurrence, and 76% 5-year actuarial disease-free survival; tumor of more than 9 mm had 53% subclinical nodal metastasis, 24% local recurrence, and 66% 5-year actuarial disease-free survival. CONCLUSIONS: Tumor thickness should be considered in the management planning of patients with early oral tongue carcinoma.     

Superficial bladder tumors (stage pTa, grades 1 and 2): the importance of recurrence pattern following initial resection

We treated 414 new patients with stage pTa, grades 1 and 2 bladder tumors by transurethral resection between 1970 and 1982. All of the patients with grade 3 or previous upper tract tumors, or who had been treated at some stage with intravesical chemotherapy were excluded. Followup for 5 or more years was available in 188 of the patients. There was a low increase in T stage (6 per cent). Of the patients followed for 5 or more years 46 per cent remained free of tumor. Only 16 per cent of the patients had multiple tumors at presentation and 20 per cent had tumors of 10 gm. or more. These factors were associated with a worse prognosis. Patients free of tumor at 3 months had an 80 per cent chance of having no further recurrences and this rate remained the same up to 2 years from the start of the disease. Patients with a recurrence at 3 months were much less likely to remain free of tumor, and had a higher chance of recurrence at every future visit.     

Postoperative Radiation Therapy in 26 Patients with Invasive Transitional Cell Carcinoma of the Upper Urinary Tract: No Impact on Survival?

Purpose

To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus postoperative prophylactic irradiation for such a tumor.

Materials and Methods

Between February 1980 and October 1993, 18 men and 8 women (mean age 65 plus/minus 9 years, standard deviation) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58 percent). The tumor was pathological stage B in 11 patients (42 percent) and stage C in 15 (58 percent). Tumor grade was 2 in 10 patients, 3 in 15 and unknown in 1. One patient had epidermoid metaplasia of urothelial cancer and 9 had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy. to the tumor bed²³ and/or regional nodes¹⁸.

Results

After a mean followup of 45 months 13 patients (50 percent) were alive and 11 were disease-free at analysis. Local tumor relapse, nodal recurrence and metastasis were noted in 1, 4 (15 percent) and 14 (54 percent) patients, respectively. All patients with nodal recurrence had metastasis. A secondary location was noted frequently (6 bladder, 1 contralateral renal pelvis and 1 urethral tumors). Overall 5-year survival rate and 5-year survival rate with no evidence of disease were 49 percent and 30 percent, respectively. Overall 5-year survival rates were 60 percent for stage B and 19 percent for stage C disease (p = 0.07), 49 percent for node-negative versus 15 percent for node-positive cancer (p = 0.04), and 90 percent for grade 2 and 0 percent for grade 3 tumors (p less than 0.01).

Conclusions

In our trial using a radio-surgical approach, local control of disease and survival rates were similar to those reported previously in surgical series. Prophylactic postoperative radiation therapy is not recommended except in prospective randomized studies.