Characterization of bladder papilloma by two-parameter DNA-RNA flow cytometry.

Two-parameter flow cytometry (FCM) studies of 0.9% NaCl solution bladder irrigation specimens were performed on 48 patients with histologically orderly or atypical papilloma of the urinary bladder in order to assess the value of RNA as a possible second parameter, along with DNA, in the detection of bladder tumors. DNA, RNA, and nuclear diameter measurements were obtained for each of 5000 cells/sample, and analyses were based on the distributions of those values. With the use of DNA content alone, 22 cases (46%) were classified positive by FCM. With RNA content as an additional parameter, 40 cases (83%) were positive. Two cases were suspicious, and 6 cases were normal by both parameters. Of 28 patients with papillomas showing histological atypia, 16 patients had positive DNA histograms, including 3 patients with aneuploid stemlines, but 24 of the 28 patients had positive RNA histograms. Of 20 patients with orderly papillomas, 6 patients had positive DNA histograms, including 3 patients with aneuploid DNA stem cell lines, but 16 of the 20 patients had positive RNA histograms. Thus, the probability of positive DNA histograms is higher in atypical papillomas (57%) than in orderly papillomas (30%), whereas elevated (positive) RNA is more characteristic of all papillomas without distinction between those that are histologically atypical (86% positive) or orderly (80% positive). For patients at risk of developing papillary bladder tumors, two-parameter DNA-RNA FCM appears to offer greater diagnostic sensitivity than does FCM based on DNA content alone.

Paternity in men with stage I testis tumors on surveillance.

PURPOSE: We report long-term paternity in men with stage I testis tumors who were managed initially by surveillance. PATIENTS AND METHODS: One hundred five patients with clinical stage I nonseminomatous germ cell tumors of the testis were entered on a surveillance protocol and followed up for more than 10 years. Actual fertility potential was assessed by pregnancy. RESULTS: Of the 105 patients, 41 (39%) have fathered children, which includes 36 of 78 (46%) patients while on active surveillance and five of 27 (19%) patients after treatment for relapse. Of 63 couples who attempted a pregnancy on surveillance or were presumed capable of impregnation (whether they tried or not), 41 (65%) were successful. CONCLUSION: These results show that the majority of men with stage I testis tumor who are on surveillance after orchiectomy, have a suitable partner, and attempt impregnation achieve a successful pregnancy. Pregnancy rates appear to be less than reported in men who have a nerve-sparing retroperitoneal lymph node dissection (RPLND) because more patients on surveillance require treatment for relapse, which reduces their chances for pregnancy.

Bacillus Calmette-Guérin therapy alters the progression of superficial bladder cancer.

The effectiveness of BCG in preventing disease progression in patients with superficial bladder cancer is evaluated. Long-term follow-up of high-risk patients treated in a previously reported randomized control trial of intravesical plus percutaneous BCG shows that progression occurred in 41/43 (95%) of control and 23/43 (53%) of BCG-treated patients. Muscle invasive and/or metastatic disease occurred with equal frequency in the two groups, but was significantly delayed by BCG treatment (P = .012). Cystectomies were required in 18/43 (42%) control and 11/43 (26%) BCG-treated patients. Median time to cystectomy was 8 months for control v 24 months for BCG-treated patients. Based on initial treatment, survival was improved by BCG therapy (P = .032) (median follow-up 6 years). These results suggest that in high-risk patients intravesical BCG can delay disease progression, prolong the period of bladder preservation, and increase overall survival.

Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.

Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial.

PURPOSE: Superficial bladder tumors (stage Ta, T1, and Tis) may progress to invade the bladder muscle and cause death from metastatic cancer. Transurethral tumor resection (TURB) is the standard therapy for such tumors, but surgery alone may not prevent tumor progression. Intravesical therapy is widely used as an adjunct to TURB. Bacillus Calmette-Guérin (BCG) is the most active intravesical agent, but whether BCG prevents tumor progression and death from bladder cancer is unknown. PATIENTS AND METHODS: Between 1978 and 1981, 86 high-risk patients with superficial bladder cancer were randomly assigned to receive either TURB (n = 43) or TURB plus BCG (n = 43). Adverse tumor features for progression were equally distributed between the two groups. BCG was administered weekly for 6 weeks. Patients were evaluated every 3 to 6 months thereafter for progression to muscle invasion or metastasis. Control (TURB) patients with recurrent superficial tumors were eligible for crossover to the BCG arm. All patients have been monitored until event or for a minimum of 10 years (range, 10 to 14). RESULTS: The 10-year progression-free rate was 61.9% (95% confidence interval [CI], 47.2% to 76.7%) for patients treated with BCG and 37% (95% CI, 22.9% to 53.1%) for control patients. The median progression-free interval was not reached for the BCG group and was 46 months for the control group (P = .0063). Of 18 control patients crossed over to BCG (median, 29 months), 15 did not show tumor progression. TURB plus BCG resulted in a 10-year disease-specific survival rate of 75%, compared with 55% with TURB alone (P = .03). CONCLUSION: This study shows that intravesical therapy with BCG delays tumor progression and death from tumor in patients who present with superficial bladder cancer.

Presumptive downstaging from preoperative irradiation for bladder cancer as determined by flow cytometry: preliminary report.

Presumptive tumor downstaging was evaluated in 28 patients with grade II or III, solid, muscle-infiltrating bladder cancer (clinical category T3) treated by integrated irradiation (2000 rad to the whole pelvis in 5 days) and cystectomy (1-14 days later) by comparing the results of flow cytometry (FCM) on barbotage specimens obtained before and after irradiation (at the time of cystectomy) and the results of pretreatment clinical stage (T category) and post cystectomy pathological stage (P category). The patients were divided into three groups: (1) P greater than T, (2) P = T, and (3) P less than T. All of the patients in this study had positive FCM specimens with an aneuploid stemline in the pre-irradiation specimen. A complete radiation response (CRR) was defined by FCM as disappearance of the aneuploid stem cell line. Of the 5 patients in the P less than T group, 4 showed a CRR; of 20 patients in the P = T group, 8 showed a CRR; of the 3 patients in the P greater than T group, none showed a CRR. The proportion of patients in the various T/P groups is consistent with that previously observed in patients receiving integrated irradiation (2000 rad in 5 days) and cystectomy (1-14 days later). The overall downstaging response of 43%, as determined by FCM, correlates well with the pathological downstaging rates of 40%-68% reported by others following high dose (4000-5000 rad) integrated irradiation cystectomy regimens; however, it is more than the 27% rate reported with the low dose short course (2000 rad in 5 days) regimen. The correlation of the FCM findings with clinico-pathological downstaging is consistent with the possibility that FCM may be useful in identifying a favorable radiation response.

Basal cell carcinoma of scrotum.

Two cases of basal cell carcinoma of the scrotum are reported. Wide local excision of the lesion is all that is necessary as primary treatment because regional lymph node metastases are seldom seen.

Advanced prostatic carcinoma: flutamide therapy after conventional endocrine treatment.

Twenty-six patients with advanced prostatic carcinoma refractory to conventional endocrine treatment were treated with a new oral nonsteriodal antiandrogen, flutamide. There were 6 responders and 20 failures. No serious toxicity attributable to flutamide was observed.

Lymphocele after pelvic lymphadenectomy for urologic cancer.

Pelvic lymphadenectomy is used widely for staging prostatic or bladder carcinoma. In 9 of 187 patients (4.7 per cent) who underwent bilateral pelvic lymphadenectomy for urologic cancer pelvic lymphocele diveloped. The management of these patients is presented along with review of causes, clinical features, diagnosis, and treatment. Pelvic CT scan is a noninvasive modality which aids in the diagnosis of this complication. Minidose heparin used for prophylaxis of thromboembolic complications may increase lymphocele formation.

Father-son testicular (teratocarcinoma) malignancy.

A case report of father-son testicular cancers, both teratocarcinomas, is presented and genetic considerations discussed.

Gleason grading of prostate cancer: a predictor of survival.

The Gleason grading system was employed in the pathologic assessment of 82 patients with carcinoma of the prostate diagnosed between 1962-1965 and subsequently followed to death. The data suggest that the Gleason grade gives long-term prognostic information independent of stage with a direct correlation between increasing Gleason grade and cancer death rate index. Furthermore, the sum of clinical stage plus Gleason grade is a more significant prognostic factor than either stage or grade alone.

Evolution of the management of stage I nonseminomatous germ-cell tumors of the testis.

The sequence of treatment modalities for stage I nonseminomatous germ-cell cancer presented herein represents the evolution of treatment over the past three decades: from retroperitoneal lymphadenectomy or radiation therapy to surveillance to modified retroperitoneal lymphadenectomy or nerve-sparing retroperitoneal lymphadenectomy. Each new concept has prompted investigators to critically assess patient eligibility criteria and predictors of response and relapse. Primary predictors of treatment success have been local tumor stage (T status), the presence of vascular or lymphatic invasion, and primary tumor histology. These studies have also allowed critical review of the accuracy of radiologic staging, which, although markedly improved over the past decade, remains imperfect. With the advent of effective chemotherapy and improved patient salvage at relapse, these studies have allowed quality of life issues to become incorporated into management decisions. If there can be one conclusion concerning the management of stage I nonseminomatous germ-cell cancer, it must be that there is no one best treatment for all patients. Each treatment is associated with advantages and disadvantages. The treatment therefore should be individualized for each patient. As patients are evaluated, emphasis must be placed on the identification of relapse risk factors through meticulous pathologic review and accurate radiologic staging. Thus, the patients with clinical stage I disease and unfavorable prognostic factors (such as the presence of vascular invasion in the primary tumor, embryonal carcinoma, T2-T4 tumor) should be advised to undergo retroperitoneal lymphadenectomy; if the nodes are negative on frozen section, then modified retroperitoneal lymphadenectomy or nerve-sparing retroperitoneal lymphadenectomy should be performed; otherwise, bilateral retroperitoneal lymphadenectomy would provide the best chance of cure. Patients with stage I disease and favorable prognostic factors (such as T1 tumor, teratocarcinoma, absence of vascular invasion in the primary tumor) are suitable for either surveillance or modified or nerve-sparing retroperitoneal lymphadenectomy; these options should be thoroughly explained to the patient before any decision is made. Future efforts in this field may take a number of directions. As fertility remains a paramount issue to most patients, long-term studies will be necessary to investigate changes in semen characteristics and eventual paternity in patients followed on surveillance protocols or after either nerve-sparing or modified retroperitoneal lymphadenectomy. With continuing improvements in chemotherapy--improved efficacy with reduced toxicity--pathologic, radiographic, or serologic predictors of the site of eventual relapse will become of increasing importance. Indeed, if patients can be identified who are at a significant risk of distant relapse, an initial chemotherapy protocol may be warranted.(ABSTRACT TRUNCATED AT 400 WORDS)

Treatment of advanced prostatic cancer.

Many treatment modalities are available to patients with disseminated adenocarcinoma of the prostate. Although no single therapeutic approach can be advocated for all patients at the present time, delay of endocrine manipulation until the onset of symptoms is the recommended approach because it maintains the most normal lifestyle in these patients. With the onset of symptoms such as bone pain or urinary retention, or perhaps as disease progression becomes apparent, orchiectomy is recommended to patients with increased cardiovascular risks as well as to those patients who are judged irresponsible in taking oral estrogens. A dose of 1 mg of diethylstilbestrol three times daily achieves a castrate level of serum testosterone and may not increase cardiovascular mortality. Because of the relative safety and lack of side effects, GnRH analogues represent an alternative treatment in selected patients, particularly in those who refuse orchiectomy or have an increased risk of developing cardiovascular complications. Hormonal manipulation with androgen deprivation remains the cornerstone of treatment and provides clinical remission in the majority of patients with advanced prostate cancer. The prognosis is poor once tumor has recurred. Several secondary forms of endocrine therapy are available, but it would help to be able to select those patients with hormonally sensitive tumors that would respond favorably to these modalities. Transurethral surgery and radiotherapy are effective in palliating patients with bladder outlet obstruction and bony metastases unresponsive to hormonal therapy. Nonhormonal cytotoxic agents are available, but well-controlled studies are required to determine the value of specific agents, whether used alone or in combination.

Flutamide and other antiandrogens in the treatment of advanced prostatic carcinoma.

The various clinical trials suggest that the qualitative and quantitative responses of patients with Stage D prostatic carcinoma to antiandrogens are similar to those achieved with conventional endocrine therapy. These antiandrogens appear generally safe and many avoid the increased risks of cardiovascular or thromboembolic complications seen with estrogen therapy. Further, flutamide appears to have a lesser adverse effect on libido and sexual potency than do alternative therapies. Antiandrogens offer an alternative mode of therapy for previously untreated patients with advanced prostatic cancer but have produced no convincing benefits in hormonally refractory patients.

Experience with interstitial implantation of iodine 125 in the treatment of prostatic carcinoma.

Between February 1970 and April 1977 300 patients with localized prostatic carcinoma were treated with I-125 implantation and bilateral pelvic lymphadenectomy at Memorial Sloan-Kettering Cancer Center (MSKCC). 68% had clinical Stage B (T-1 and T-2) and 32% had Stage C (T-3) neoplasms. Pelvic lymph nodes were histologically positive in 38% of the patients. Five-year survival for all patients was 73%. Five-year survival for Stage B disease was 100% and Stage C 65%. Lymph node metastases implied a poor prognosis. While 92% of patients with negative nodes survived five years, only 46% of the patients with positive nodes did so. Supplemental external radiation to pelvic and periaortic region in 28 patients with positive nodes did not improve survival or disease free interval or reduce distal or local recurrence but rather increased the incidence of radiation morbidity. The complications and morbidity as a consequence of I-125 implantation are minimal. The ultimate role of I-125 implantation in the management of localized prostatic cancer is yet to be determined. The early experience with this technique, however, suggests that it may be as effective as alternative modalities for comparable stages in terms of patient survival and may prove superior in terms of the quality of survival.

Does early cystectomy improve the survival of patients with high risk superficial bladder tumors?

PURPOSE: We compared survival after early versus delayed cystectomy in patients with high risk superficial bladder tumors. MATERIALS AND METHODS: Of 307 patients with high risk superficial bladder tumors who were treated initially with transurethral resection and bacillus Calmette-Guerin (BCG) therapy 90 (29%) underwent cystectomy for recurrent tumor during a followup of 15 to 20 years. Disease specific survival distribution of these 90 patients was determined relative to the indications for and time of cystectomy. RESULTS: Of the 90 patients who underwent cystectomy 44 (49%) survived a median of 96 months. Of 35 patients with recurrent superficial bladder tumors 92% and 56% survived who underwent cystectomy less than 2 years after initial BCG therapy and after 2 years of followup, respectively. Of 55 patients with recurrent muscle invasive bladder disease 41% and 18% survived when cystectomy was performed within and after 2 years, respectively. Multivariate analysis showed that survival was improved in patients who underwent earlier rather than delayed cystectomy for nonmuscle invasive tumor relapse. CONCLUSIONS: Earlier cystectomy improves the long-term survival of patients with high risk superficial bladder tumors in whom BCG therapy fails.

Solitary vaginal metastasis from unsuspected renal cell carcinoma.

Four cases of solitary vaginal metastasis from previously unsuspected renal cell carcinoma are presented. Vaginal bleeding, the presenting symptom in each patient, led to the finding of the metastatic vaginal lesion and to the urological evaluation, which revealed the occult primary renal cell carcinoma. With surgical treatment 2 of the 4 patients have remained well for more than 5 years.

Experience with flutamide in previously untreated patients with advanced prostatic cancer.

Twenty-one patients with advanced prostatic adenocarcinoma previously untreated with conventional endocrine therapy were treated with an oral non-steroidal antiandrogen, flutamide. There were 19 favorable responders, 1 failure and 1 equivocal response. Flutamide seems to be a safe antiandrogen, which is effective in the management of previously untreated patients with advanced prostatic carcinoma.

Association of primary germ cell tumor of the testis and renal cell carcinoma.

The combined presentation of 2 separate neoplasms is rare. We report 3 cases of primary testicular cancer that were associated with renal cell carcinoma and discuss their management.