Nuclear DNA analysis: DNA heterogeneity in the monitoring of patients with locally advanced prostatic carcinoma.

Single-cell DNA cytophotometry was employed to analyze the tumors of 271 patients with locally advanced prostatic carcinoma as to DNA ploidy and heterogeneity and the distribution of the phases of the cell cycle before and during therapy, with the intention of establishing prognostic factors apart from those already known (stage, grade). Follow-up periods ranged from 1 to 9 years. 198 (73%) of the 271 patients had carcinoma stage T3 N0 M0, and 73 (27%) of them had carcinoma stage T3/T4 N+M1. The tumors were evaluated cytologically to establish the grades of malignancy. 11.8% were grade I carcinoma, 64.3% were grade II and 23.9% were grade III carcinoma. Single-cell DNA cytophotometry demonstrated aneuploidy rates of up to 73% and diploidy rates of up to 23.8% for the higher grades of malignancy, whereas the diploidy rate established for grade I carcinoma was 71% and the respective aneuploidy rate was 15.2%. These differences are significant (p < 0.001). There was a significant correlation between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei developed no metastases and no local tumor progression during the follow-up period of 9 years, whereas patients with aneuploid tumor cell nuclei showed metastases and local tumor progression within 8-22 months, despite changes in therapy. These patients died of carcinoma after an average 18 months following primary diagnosis.     

Prognostic relevance of DNA ploidy and proliferative activity in urothelial carcinoma of the renal pelvis and ureter. A study on a follow-up period of 6 years

In 55 patients with urothelial carcinoma of the renal pelvis or ureter, the ploidy, the DNA heterogeneity and the counts of cell cycle phases in the tumor were examined by means of single-cell DNA cytophotometry in order to find more prognostic factors than those already known (stage and grade). Follow-up periods ranged from 1 to 6 years. At the time of first diagnosis, 42 (76%) of the patients had tumors of the renal pelvis, 13 (24%) of them had ureteral tumors. 23 (42%) patients were in stage pT 1 N 0, 15 (27%) in stage pT 2 N 0, 12 (22%) in stage pT 3 N 0, and 5 (9%) were in stage pT 3 N+. The histological malignancy grade most frequently seen in the patients examined--i.e. in 51% of cases--was malignancy grade II. 25% of the patients had grade III tumors whereas only 24% had grade I tumors. With malignancy grade I, DNA cytophotometry showed DNA frequency peaks to be in the diploid range while tumors with malignancy grade II showed heterogenous DNA patterns. 71% of the patients with malignancy grade III showed aneuploid DNA values; 29% of them had polyploid DNA values. For malignancy grades II and III, the proliferation rate of the tumor cells was statistically significantly higher than for malignancy grade I. The determination of tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry gives valuable clues regarding prognosis.     

Nuclear DNA analysis: the relevance of ploidy, DNA heterogeneity and phases of the cell cycle in 329 patients with prostatic carcinoma. A study on a follow-up of eight years

The ploidy, DNA heterogeneity and the phases of the cell cycle of the tumor were analyzed, by means of single-cell DNA cytophotometry, in 329 patients with locally advanced prostatic carcinoma to find out and establish prognostic factors apart from those already known (stage, grade). Follow-up periods ranged from 1 to 9 years. 253 (76.8%) of the 329 patients had carcinoma stage T3 Nx M0, and 76 of them (23.1%) had carcinoma stage T3/T4 N2-4 M1. 11.8% of the patients showed a cytological grade of malignancy I, while 64.3% had grade II carcinoma and 23.8% had grade III carcinoma. Single-cell DNA cytophotometry demonstrated aneuploidy rates of up to 71% and diploidy rates of up to 23.8% for the higher grades of malignancy, i.e. grades II and III, whereas the diploidy rate established for grade I was 68% and the respective aneuploidy rate was 21%. These differences are significant (p less than 0.001). There was a significant correlation between the results of DNA cytophotometry and the clinical course of the disease. Only 3 (3.7%) of the patients with diploid tumor cell nuclei developed metastases and local tumor progression within 8 years, whereas patients with aneuploid tumor cell nuclei showed metastases and local tumor progression within 8-22 months. These patients died of carcinoma after an average 18 months following primary diagnosis.     

Value of nuclear DNA ploidy patterns in patients with prostate cancer after radical prostatectomy.

Flow cytometric analysis of DNA ploidy was performed on prostatic adenocarcinoma specimens from 80 patients. In all these patients a radical retropubic prostatectomy had been performed. The nuclei for DNA ploidy determination were extracted from paraffin-embedded material of whole sections of the prostate from patients treated by radical prostatectomy between 1980 and 1985. DNA ploidy was a strong prognostic indicator independent of tumor grade and tumor stage. DNA ploidy offered additional information on both tumor stage and tumor grade. In stage C disease the likelihood of progression-free survival was 89.5% in diploid tumors and 27.8% in aneuploid tumors after 9 years. In tetraploid tumors all patients progressed after 9 years. The computed survival rates in stage C disease showed that patients with diploid tumors did significantly better than those with aneuploid or tetraploid tumor patterns. These data indicate therefore that DNA ploidy patterns determined by flow cytometric analysis provide important additional prognostic information on prostatic adenocarcinoma treated by radical prostatectomy.     

Flow cytometric deoxyribonucleic acid analysis in stage I renal cell carcinoma

Tumor deoxyribonucleic acid (DNA) content was analyzed by flow cytometry in 60 consecutive patients with stage I renal cell carcinoma. Of 59 evaluable tumors 27 (46%) were homogeneously diploid, 1 (2%) was tetraploid and 31 (52%) were aneuploid. Of the 32 nondiploid tumors 25 were heterogeneous concerning ploidy. One of the 27 patients with diploid tumors had metastases compared to 5 of the 32 patients with nondiploid tumors (not significant). There was a significant difference in survival between patients with diploid and nondiploid tumors (p = 0.043). Neither nuclear grade, tumor cell type nor tumor size correlated with survival. Analysis of DNA content seems to predict survival significantly for patients with stage I renal cell carcinoma.     

Renal cell carcinoma: DNA cytometry and its clinical significance. An 8 year survival study]

In 157 patients with renal cell carcinoma, the ploidy, DNA heterogeneity and the phases of the cell cycle occurring in the tumors were determined by means of single-cell DNA cytophotometry, in order to establish further prognostic factors in addition to the ones known so far (stage/grade). Patients with aneuploid tumors or tumors with more than one DNA frequency peak were found to have lymph node metastases intraoperatively and died earlier than patients with diploid tumors. Patients who had tumors with low proliferative activity survived longer than patients with highly proliferative tumor activity (p = 0.001).     

DNA ploidy as a prognostic factor in muscle invasive transitional cell carcinoma of the bladder

Radical cystectomy represents the treatment of choice for muscle-infiltrative bladder carcinoma; however, about 50% of patients relapse and die from the disease. In the present study, the prognostic significance of the DNA ploidy in transitional cell carcinoma of the urinary bladder (TCCB) is analyzed. The study was carried out on 66 patients with TCCB who underwent radical cystectomy. DNA ploidy was determined by flow cytometry (FCM) on paraffin-embedded specimens, and the results were analyzed and correlated with the tumor malignancy grade and stage and the clinical course. Forty of the 66 tumors studied (63%) were aneuploid. Aneuploid status was correlated with higher tumor T stage (P<0.001) and grade (P<0.001). Median follow up was 68 months (range: 12–105). Median survival was significantly longer in patients with diploid tumors (>60 vs 45 months, P<0.001). All patients with diploid tumors were alive and free of bladder cancer during follow-up, in contrast to only 30% of patients with aneuploid tumors. DNA ploidy was an independent prognostic factor, as shown by multivariate analysis (P=0.006). All patients with pT3b and diploid tumors were alive at the time of analysis as opposed to none with aneuploid tumors. The results of this study suggest that DNA ploidy can provide prognostic information on patients with muscle invasive carcinoma of the bladder and might represent a means of selection for postoperative management.     

Flow cytometric assessment of deoxyribonucleic acid content in renal adenocarcinoma: does ploidy status enhance prognostic stratification over stage alone?

Flow cytometry was used to analyze deparaffinized primary renal cell carcinoma specimens from 106 patients to evaluate deoxyribonucleic acid ploidy as a predictor of disease progression and survival. Of these specimens 62 (58%) demonstrated aneuploid stem lines: 30 (48%) of these were tetraploid aneuploid while 32 were nontetraploid aneuploid. Two or more specimens were analyzed from a single primary tumor in 17 patients and heterogeneity of ploidy status was observed in 5 (30%). Specimens of the primary tumor, and regional and/or distant metastases from 11 patients were analyzed; 5 (45%) demonstrated discordance between the ploidy of the primary and the metastatic site. A significant correlation was noted between the presence of aneuploid stem lines and high stage disease (p equals 0.004) but there was no significant correlation between ploidy status and tumor grade. Although there was a significant difference (p equals 0.037) in the incidence of disease progression in patients with diploid tumors (13%) versus those with aneuploid tumors (35%) in the total population, and Kaplan-Meier disease-specific survival curves demonstrated a survival advantage for patients with diploid tumors in the total population, no clear survival advantage was demonstrated for evaluable patients with diploid tumors when controlled for tumor, nodes and metastases stage. In conclusion, the heterogeneity of ploidy status in primary renal cell carcinoma, the high incidence of disease progression in patients with diploid primary tumors and the lack of a clearly demonstrable stage-independent impact of ploidy on prognosis currently would not support widespread clinical application of ploidy status of the primary tumor in the management of individual patients with renal cell carcinoma.     

Prognostic relevance of ploidy and proliferative activity of renal cell carcinoma

In 112 patients with renal cell carcinoma, the ploidy, DNA heterogeneity and the phases of the cell cycle occurring in the tumors were determined by means of single-cell DNA cytophotometry, in order to establish further prognostic factors in addition to the ones known so far (stage/grade). Patients with aneuploid tumors or tumors with more than one DNA frequency peak were found to have lymph node metastases intraoperatively and died earlier than patients with diploid tumors. Patients who had tumors with low proliferative activity survived longer than patients with highly proliferative tumor activity (p = 0.001).     

Squamous cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry

From 1944 to 1987, 28 patients with squamous cell carcinoma of the upper urinary tract were treated and also had tumor specimens that were fully evaluable by flow cytometric nuclear deoxyribonucleic acid ploidy analysis: 22 had squamous cell carcinoma of the intrarenal collecting system, 4 had tumors of the ureter, and 2 had tumors of the renal pelvis and ureter. Eight patients (29%) had deoxyribonucleic acid diploid, 11 (39%) tetraploid and 9 (32%) aneuploid ploidy patterns. Ploidy pattern significantly correlated with histological grade and tumor stage. Almost all tumors were histologically of high grade; among the patients with high grade tumors ploidy analysis separated fair and poor prognosis groups. Pathological stage was the dominant clinical variable. A total of 14 patients (50%) had advanced stage disease and all died within 12 months of diagnosis. Nearly all of these patients showed abnormal ploidy patterns and ploidy analysis was not useful prognostically for this group. In contrast, all 3 patients with squamous cell carcinoma of the renal pelvis who were long-term survivors had deoxyribonucleic acid diploid tumors. However, there is no clear statistical evidence from this study that ploidy analysis provides important prognostic information independent of stage and grade for patients with squamous cell carcinoma of the renal pelvis.     

Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis

Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10 (4%). The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer.     

Primary adenocarcinoma of the bladder: favorable prognostic significance of deoxyribonucleic acid diploidy measured by flow cytometry

Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy.     

Dna heterogeneity determined by flow cytometry in prostatic adenocarcinoma—necessitating multiple site analysis

Although DNA ploidy analysis of prostate cancer is generally associated with grade, stage, clinical outcome, and responsiveness to androgen therapy, one possible reason cited for contrary reports may be tumor heterogeneity. A preliminary report using flow cytometric analysis of punch biopsies demonstrated DNA heterogeneity in five of nine patients. We evaluated 75 patients by cutting whole mounts of formalin fixed prostatectomy tissue every 0.6 cm. All malignant areas and a selected normal area were circumscribed, excised, remounted, and 1–3 50 μ thick sections removed. The nuclei were extracted by a Hedley technique and the DNA stained with propidium iodide. Each whole mount had an average of 1 distinct malignant area (range of 1–6 areas per whole mount block). Nuclei were analyzed on a Becton Dickinson (San Jose, CA) FACScan flow cytometer equipped with RFIT DNA software program. After excluding histograms with CVs > 8.0% and/or “suspicious” diploid histograms having a right “shoulder,” 75 or 87 patients still had ≥2 malignant sites available for analysis (average 4, range 2–9 malignant sites/patient). The 322 histograms had an average CV of 4.4%. Thirty of 75 patients (40%) showed DNA heterogeneity in multiple samples taken from the same prostate. There were 37 prostates with only diploid (D), 1 with only tetraploid (T), 7 with only aneuploid (A), 20 with D plus A, 7 with D plus T, 2 with D plus T plus A, and 1 with a D plus suspected hypodiploid DNA content. Exclusion of the tetraploid and “near diploid aneuploid” cases still resulted in 16% (12/75) of the patients having a diploid versus aneuploid DNA content heterogeneity. Because 40% of the prostates contained a different ploidy depending on which area was sampled, this report suggests multiple sites of malignancy must be analyzed to more accurately assess the ploidy status of prostatic adenocarcinoma. © 1995 Wiley-Liss, Inc.     

Relationship of nuclear DNA content to clinical and pathologic findings in patients with primary hepatic malignancy.

BACKGROUND. Nuclear DNA content of a variety of tumors has proven valuable as a prognostic indicator. The purpose of this study was to analyze patterns of DNA content in primary hepatocellular carcinoma and to correlate ploidy status with patient survival. METHODS. The relationship of nuclear DNA content to host and tumor characteristics was analyzed in 46 patients with primary hepatic malignancy who had undergone resection with curative intent between 1975 and 1985. RESULTS. Flow cytometric measurement of tumor DNA content revealed a diploid pattern in 33%, tetraploid or polyploid in 30%, and aneuploid in 37% of cases. There was no significant correlation between tumor DNA content and demographic or pathologic findings in the patients studied. Moreover, there was no difference in survival between patients with diploid versus nondiploid tumors. CONCLUSIONS. These findings suggest that tumor DNA content has no prognostic value in patients with primary hepatic malignancy.     

Clinical significance of flow cytometric deoxyribonucleic acid measurements of deparaffinized specimens in bladder tumors.

A retrospective study of flow cytometric measurements on paraffin-embedded tumor specimens from 188 patients with bladder tumor was conducted. Results were analyzed in combination with the morphological variation in bladder tumors. It was found that the deoxyribonucleic acid (DNA) ploidy pattern, the degree of infiltration and the multiplicity of bladder tumor were closely related with tumor recurrence, among which the DNA ploidy pattern was most significant. In aneuploid bladder tumors, the recurrence rate and the mean annual recurrence frequency were 76.7% and 1.46, respectively, and in the diploid bladder tumors, they were 18.7% and 0.33, respectively. Aneuploidy was the most indicative parameter of recurrence in bladder tumors. In addition, according to the DNA content and the ploidy level of the aneuploid cell lines, the aneuploid tumors in our group were divided into four types, namely tetraploid tumors, noneuploid tumors with an DNA index (DI) less than or equal to 1.5, hypotetraploid tumors and aneuploid tumors with several cell lines. The results showed that the recurrence rate of tetraploid tumors was relatively lower, and it became higher and higher in the following order: noneuploid tumors with DI less than or equal to 1.5, noneuploid tumors with DI greater than 1.5, and two-aneuploid tumors. This indicates that there are different biological behaviors in tumors with different ploidy patterns. Finally, the correlation between the DNA ploidy pattern and tumor metastases was also discussed.     

Transitional cell carcinoma of the upper urinary tract: evaluation of prognostic factors by histopathology and flow cytometric analysis

Prognostic factors in transitional cell carcinoma of the upper urinary tract were assessed with histopathological examination and flow cytometric analysis in a series of 127 patients operated upon between 1976 and 1988. In particular, we evaluated the usefulness of flow cytometry to identify patients who require adjuvant treatment among those with low grade and low stage disease (51% in this series). A multivariate analysis was done on 92 cases, considering patient age and sex, stage, grade and number of lesions (unifocal versus multifocal), site (renal pelvis versus ureter), presence of vesical tumors, recurrences along the urinary tract or in the bladder, type of operation and nuclear deoxyribonucleic acid (DNA) ploidy (diploid versus tetraploid/aneuploid tumors). Only the stage (p = 0.001), grade (p = 0.001) and, to a lesser extent, the DNA pattern (p = 0.031), as well as the number of lesions (p = 0.061) were determinant for prognosis. In regard to the subgroup of 41 patients with grade 2 or less, stage P1 or less tumors, no significant difference in survival was demonstrated between diploid and nondiploid tumor patients. However, 7 of 10 patients from the latter group are still under observation. Therefore, our conclusions may have to be modified in the future.     

Adrenocortical carcinoma: nuclear deoxyribonucleic acid ploidy studied by flow cytometry

Nuclear deoxyribonucleic acid (DNA) ploidy studies with use of paraffin-embedded specimens were performed by flow cytometry on 52 adrenocortical carcinomas. Specimens were prepared by the combined techniques of Hedley and Vindel?v. Clinical course was obtained by chart review and follow-up examination. Nine (17%) tumors had a normal (diploid) DNA pattern, 13 (25%) were DNA tetraploid, and 30 (58%) were DNA aneuploid. The DNA aneuploid group was subdivided: 18 tumors with one stemline and 12 tumors with two stemlines of abnormal DNA cells. For tumors that were resected for cure, the 5-year Kaplan-Meier disease-free survival rates of the five patients with DNA diploid tumors and of the six patients with DNA tetraploid tumors were 80% and 33%, respectively. For 21 patients of whom 12 had one-stemline and nine had two-stemline DNA aneuploid tumors, the survival was 67% and 0%, respectively. Following palliative resection, the 4-year survival rates of the four patients with DNA diploid, seven with DNA tetraploid, five (omitting one with short follow-up) with one-stemline DNA aneuploid, and three with two-stemline DNA aneuploid tumors were 0%, 0%, 0%, and 33%, respectively. Although adrenocortical carcinoma is in general markedly aggressive, the addition of nuclear DNA ploidy studies may help to identify certain groups of patients who have a relatively favorable prognosis.     

The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma

This study was designed to compare the prognostic potential of tumor grade and ploidy status in patients with stage D2 prostate cancer. Two outcome groups were selected on the basis of survival after orchiectomy: a bad outcome group consisting of 66 patients who died of the disease within 12 months and a good outcome group comprising 37 patients who survived beyond 5 years. Tumors were classified histologically as well (17%), moderately (17%) or poorly (66%) differentiated. Tumor grade was a significant predictor of outcome, with 76% of poorly differentiated tumors in the bad outcome group and 65% of well differentiated tumors in the good outcome group (p less than 0.005). Deoxyribonucleic acid (DNA) ploidy analysis was performed on formalin fixed, paraffin embedded samples of the primary tumor to yield 97 final tracings that were classified using set criteria for DNA ploidy status. Over-all, 54% of the tumors were nondiploid (33% aneuploid and 21% tetraploid) and the remaining 46% were diploid. DNA ploidy status was a significant indicator of outcome (p less than 0.001), with 64% of diploid tumors in the good outcome group and 88% of the nondiploid tumors in the poor outcome group. Tetraploid tumors behaved no differently from other nondiploid tumors. We conclude that DNA ploidy status and tumor grading are significant independent predictors of outcome after orchiectomy and when combined yield important additional prognostic information.     

The clinical usefulness of flow cytometric DNA analysis in prostatic cancer]

Flow cytometry was used to measure the DNA content in archival paraffin-embedded prostatic cancer specimens from 54 patients with known outcomes. The specimens were obtained by transurethral resection of the prostate. DNA ploidy as a predictor of prognosis was compared with histological grade and clinical stage. Although no significant correlation between histological grade or clinical stage and ploidy pattern was demonstrated, an increased percentage of DNA aneuploid tumors was seen in higher histological grade and in advanced clinical stage. The survival rate calculated by Kaplan-Meier analysis showed that DNA ploidy pattern was a more reliable indicator to predict survival probability than histological grade or clinical stage. All patients with a near diploid pattern (11 patients) survived more than 5 years, whereas all those with an aneuploid pattern (21 patients) died within 3.5 years. Of 22 patients with a tetraploid pattern, 15 died of tumor progression within 5 years. The remaining 7 patients with favorable outcome had a relatively lower proliferation index (less than 65) in DNA histogram and none of them suffered from stage D disease. In conclusion, the results from this retrospective study suggest that flow cytometric DNA analysis in prostatic cancer would be useful as a means of providing prognostic information.     

The prognostic significance of deoxyribonucleic acid flow cytometry in muscle invasive bladder carcinoma treated with preoperative irradiation and cystectomy.

Deoxyribonucleic acid (DNA) flow cytometry measurements were performed in nuclear suspensions obtained from paraffin-embedded biopsies from 83 patients with stages T2, T3 and T4a bladder carcinoma. All patients were treated with preoperative radiotherapy and cystectomy from 1976 through 1985. Of the tumors 13 (16%) were diploid, 18 (22%) tetraploid and 52 (63%) aneuploid. A total of 19 tumors (23%) had 2 or 3 stemlines in addition to the diploid cells. Post-radiotherapy stage reduction (absence of muscle infiltration in the cystectomy specimen) occurred more often in tumors with only 1 nondiploid stemline than in diploid tumors or nondiploid tumors with multiple stemlines. The 5-year survival rate was significantly poorer for patients with a diploid (33%) than for those with a nondiploid (66%) tumor (p = 0.05), although this was only marginally retained in a multivariate analysis (p = 0.11). The clinical significance of DNA ploidy in muscle infiltrating bladder cancer seems not to be as evident as has been shown for superficial bladder tumors but it may be of value in selecting patients for preoperative radiotherapy.