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In 2 cases epididymo-orchitis, indistinguishable from a testicular tumor, developed as a late (15 and 34 months, respectively) complication following use of Tice strain bacillus Calmette-Guerin for treatment of superficial bladder carcinoma. In each instance the lesion was asymptomatic and ultrasonography demonstrated a complex scrotal mass. Inguinal orchiectomy was performed for diagnosis and therapy. The importance of obtaining a mycobacterial culture for further therapy planning is stressed.

We reviewed the treatment morbidity associated with definitive high energy external beam radiotherapy in 289 consecutive patients with clinically localized prostate cancer (stages A2 to C) treated from 1984 to 1988 inclusively. All patients were treated with 18 mv. photon beams via a 4-field box technique. Radiation doses ranged from 5,858 to 6,900 cGy., with a mean dose of 6,456 cGy. and a median dose of 6,400 cGy. A total of 65 patients underwent extraperitoneal pelvic staging lymphadenectomy before radiotherapy. Complications noted in 42 patients were mild (generally trivial) in 23 and moderate in 19 (6.6%). There were no severe complications. The actuarial incidence of moderate complications was 9% at 5 years. Only 6 patients experienced symptoms for longer than 6 months. The risk of complications was not increased in patients who had undergone prior lymph node dissection, and only 2 of 65 had mild lymphedema, which resolved in both cases. We conclude that high energy external beam radiation for prostate cancer can be delivered with a low risk of serious complications, even in patients who have undergone extraperitoneal staging pelvic lymphadenectomy, provided the patients are treated to limited fields with high energy photons and at doses limited to 6,800 cGy. or less.

The preoperatively drawn sera from 84 previously untreated patients who had clinical stage C prostate cancer and underwent staging pelvic lymph node dissections were sent for monoclonal Hybritech analysis to assess the usefulness of prostate specific antigen (PSA) in predicting lymph node status. Of the 84 patients 47 (56%) had positive lymph nodes at surgery. The median PSA value for all patients with nodal metastases was 11.4 ng/.ml., and for those without it was 11.2 ng./ml. Relative to Gleason score, median PSA values were 11.35 for 2-4, 12.2 for 5-7 and 10.9 ng./ml. for 8-10. Within each M.D. Anderson grade median PSA values were 10.15 for grade I, 13.2 for grade II, 12.7 for grade III and 10.5 ng./ml. for grade IV. Simultaneously drawn preoperative frozen serum samples for 28 of these patients were independently analyzed by the Yang radioimmunoassay. Comparing Hybritech and Yang methods revealed strong statistical co-association (correlation coefficient R2 = 97.36, p less than 0.00001) but neither assay was statistically associated with nodal metastasis. Although no PSA level excluded the presence of nodal disease, we suggest that a Hybritech PSA of greater than 30 ng./ml. and a Yang PSA of greater than 50 ng./ml. may serve as a weak adjunctive marker predicting nodal metastasis.

The familial clustering of some cancers may be related to genetic factors, shared carcinogenic exposure among relatives or chance association. In cases of familial renal cell carcinoma identifying those persons at risk for renal tumors is difficult. There have been 28 family aggregates of renal carcinoma reported since 1961 but an abnormality in the constitutional karyotype has been demonstrated in the members of only 1 of these families. Since 1980 we have identified 5 more families in which a total of 12 relatives had renal cell carcinoma. However, peripheral blood karyotypes obtained from the 7 patients and 5 unaffected relatives whom we studied showed no significant abnormalities. With current laboratory techniques it is not possible to differentiate reliably familial renal tumors occurring by chance from those hereditary tumors posing a threat to remaining relatives. Therefore, in families with multiple cases of renal cell carcinoma we recommend that screening be conducted as has been suggested for families with von Hippel-Lindau's disease, with an initial renal ultrasound for family members at age 30 years and repeat examinations every 2 to 3 years.

Four cases of hypernephroma occurring in the first 2 decades of life are presented. Of these patients 3 were adolescents and 1 was a child. Angiography was used in 8 cases, including 6 that were reported previously and 2 from the present series. Sparse neovascularity, faint tumor stain and no arteriovenous shunting were the manifestations in 4 cases. Differentiation from Wilms tumor could be difficult in this circumstance.

The National Prostatic Cancer Project has randomized this study for endocrine-resistant prostatic cancer patients for treatment with standard hormonal or other therapies compared to 5-fluorouracil and cyclophosphamide. Both agents were found at the probability level of 0.05 to have a significant advantage over standard treatment in terms of objective response, subjective improvement and minimal toxicity. Additional chemotherapy protocols are currently under way. This randomized trial is the first report of such a national study completed to date. We are much encouraged by this program and believe that additional agents now under consideration will provide additionally encouraging results.

Adjuvant combination chemotherapy with cyclophosphamide, doxorubicin and cisplatin was administered to 36 patients after cystectomy for bladder cancer. Therapy was tolerated well except for 1 patient who suffered a fatal chemotherapy complication. Indications for adjuvant chemotherapy included vascular invasion of the primary tumor, perivesicular tumor involvement, invasion of adjacent pelvic viscera (vagina and prostate) and nodal metastases. There were 53 concurrently treated patients who did not receive adjuvant chemotherapy despite similar unfavorable pathological indications (high risk control group). Survival rates (61 and 73 per cent, respectively) were not significantly different for those patients treated with adjuvant chemotherapy and an additional group of 158 patients who underwent cystectomy during the study period but who had no adverse pathological findings (low risk control group). Survival rates differed significantly between the low risk (73 per cent) and high risk (38 per cent) control groups (p less than 0.001). Patients with unfavorable histological findings who received adjuvant chemotherapy had a significant survival advantage over the high risk control groups (61 versus 38 per cent, p equals 0.03). These data confirm the predictive value of post-cystectomy pathological findings and suggest that adjuvant chemotherapy with cyclophosphamide, doxorubicin and cisplatin not only prolongs the survival free of disease for patients at high risk for recurrence but it also may ultimately increase the cure fraction of such patients.

After curative chemotherapy 58 patients with metastatic germinal tumors and 2 with extragonadal germinal tumors underwent an operation either to confirm a clinical complete response or to remove a residual mass. Biomarker status was converted to negative in all patients. Retroperitoneal lymphadenectomy was done in 22 patients after a complete clinical response was achieved and in 23 after an apparent complete response was achieved except for a residual retroperitoneal mass. Thoracotomy was done for a residual mass in 13 patients, while 2 underwent bilateral thoracotomy. Scarring was found in 25 patients (42 per cent), teratoma in 14 (23 per cent) and active tumor in 17 (28 per cent). One patient with scarring and primary seminoma died of disseminated seminoma, while 1 with primary teratocarcinoma died of disseminated disease, for a false negative rate of 3 per cent. Four patients with a residual mass showed unexpected findings: 2 had granulomas in the lung, 1 had carcinoid of the lung and 1 had retroperitoneal neurofibroma. Thus, there was a 7 per cent incidence of a mass being other than scar, teratoma or residual tumor. There was 1 operative death and 10 deaths of tumor, for an 18 per cent death rate. Of the 17 patients with active tumor 9 responded to salvage chemotherapy with stable complete remission and a minimum followup of 18 months. In addition to the 60 patients the advanced disease in 10 was surgically debulked after failure of chemotherapy and this procedure was followed by salvage chemotherapy. All 10 patients died, with a median survival of 7 months. The lack of responsiveness to chemotherapy was not improved by incomplete removal of tumor.

A total of 31 men with clinical stage I nonseminomatous germ cell tumors of the testis was followed for 2 to 18 months (median 10 months) after inguinal orchiectomy. Of the patients 26 (84 per cent) have been continuously free of disease. Relapse occurred in 5 patients (16 per cent) at 2, 2, 4, 4 and 6 months, respectively, but they were rendered free of disease with combination chemotherapy. The results suggest that careful surveillance following orchiectomy is all that is required for patients who have nonseminomatous germ cell testicular tumors but no obvious regional or visceral metastases.

Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate of only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial.

Single stage radical cystectomy and ileal conduit diversion were performed on 214 patients for treatment of bladder carcinoma. The over-all operative mortality rate was only 3.3 per cent. Early complications occurred in 27.6 per cent of the patients and late complications were noted in 41.1 per cent of the patients followed 6 months or longer. We refute recent arguments for staged procedures as a necessity for reducing operative mortality and morbidity

In 28 patients with primary clinical stage II testicular carcinoma (retroperitoneal mass of less than 10 cm. in diameter) or persistently elevated levels of serum biomarkers after orchiectomy primary chemotherapy was administered followed by selective lymphadenectomy for patients with a persistent retroperitoneal mass. Of the patients 21 were treated with cyclophosphamide, doxorubicin, cisplatin/vinblastine and bleomycin, and 7 who were not candidates for this regimen received less aggressive chemotherapy. All 28 patients were free of disease after a mean followup of 93.6 weeks and a median of 89 weeks (range 28 to 199.5 weeks). No patient who achieved complete remission has had relapse. Of the 28 patients 1 had a seminoma and an elevated alpha-fetoprotein level, 15 had embryonal carcinoma (Dixon-Moore category II) and 12 had teratocarcinomas (Dixon-Moore category IV). Only 1 of the 15 patients with embryonal carcinoma required surgical exploration for a persistent radiographic abnormality, whereas 6 of the 12 patients with Dixon-Moore category IV tumors required surgical exploration (p less than 0.0147). This delayed approach did not increase surgical complications. Our experience with primary chemotherapy followed by selective lymphadenectomy for stage II testicular carcinoma resulted in universal survival. Only 8 of the 28 patients (29 per cent) required lymphadenectomy.

Lymphangiography was performed on 23 patients with malignancy in non-descended testicles, 14 of whom had seminomatous and 9 non-seminomatous tumors.Lymph node metastases were shown by lymphangiography in 8 patients: 3 in lumbar nodes, 1 in iliac nodes alone and 4 in lumbar and iliac lymph nodes. Microscopic metastases were shown in lumbar nodes at retroperitoneal lymph node dissection in 2 patients when the lymphangiograms were negative.Iliac lymph node metastases are rare in testicular tumors but may be seen in tumors of non-descended testicles, alone or in combination with lumbar metastatic disease. This information is extremely important for the radiologist as well as the clinician in the management of patients.

The survival data of 93 patients with metastatic renal carcinoma are discussed with respect to the site of metastasis and whether nephrectomy was performed as part of the initial treatment. Analysis of the cumulative survival rates revealed that nephrectomy significantly increased survival only for those patients presenting exclusively with osseous metastases. Nephrectomy did not alter survival for patients with pulmonary and/or soft tissue metastases.

The findings in 10 patients with advanced non-seminomatous testicular malignant disease in whom either complete remission or reduction in clinical stage was achieved with chemotherapy and later retroperitoneal lymphadenectomy are presented. The procedure in these selected instances allowed for a more accurate assessment of the disease status. The operative findings served as an accurate guide to determine the need for further drug therapy.

Of 7 patients with bladder carcinoma whose medical condition or disease status prevented an operation 5 had intractable vesical hemorrhage and 2 had progressive azotemia caused by ureteral obstruction. These patients were treated with pelvic irradiation of 1,000 rad single doses. Four patients received 3 doses 3 to 4 weeks apart and 1 patient received 2 doses at a 4-week interval. Prompt cessation of bleeding occurred in all patients and renal function improved in the 2 patients with ureteral obstruction.

The clinical and morphological features of 7 cases of anaplastic seminoma are reviewed. Although this tumor appears to behave more aggressively than classical seminoma, presenting with earlier metastases, it has the same prognosis when staging is taken into consideration. Radiotherapy remains the treatment of choice.

The third case of mucous-forming adenocarcinoma of the prostate with metastases to the bone is reported. The primary tumor was unresponsive to definitive radiotherapy and subsequent metastases to the lung, liver and bone failed to respond to hormonal manipulation and chemotherapy.

Lymphatic dynamics in the retroperitoneal space are altered after retroperitoneal lymph node dissection. Obstruction with or without visible collaterals is seen frequently. Lymphaticovenous communications and lymphocysts are also common findings. The immediate sequelae are of minor importance, although the mass effect of lymphocysts may be serious. The collateral pathways and lymphaticovenous anastomoses may result in the appearance of metastases in unusual sites.

This is the fifth completed randomized clinical trial of the National Prostatic Cancer Project. There were 125 patients with histologically confirmed relapsing clinical stage D prostatic cancer randomized to receive hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on the initial therapy were crossed over or randomized to receive an alternate drug. There were 98 patients available for comparison of treatments. Objective responses included patients with complete or partial regression as well as stable disease. The response rates were 35 per cent for cyclophosphamide, 30 per cent for methyl-chloroethyl-cyclohexy-nitrosourea and 15 per cent for hydroxyurea. Subjective response parameters included improvement in performance status and relief of pain. Pain was improved in a fifth of the patients on each treatment area. Methyl-chloroethyl-cyclohexy-nitrosourea and hydroxyurea showed activity in advanced prostatic cancer patients but at the expense of excessive toxicity. Cyclophosphamide continues to be the most active single agent in this type of patient, particularly with regard to duration of response and survival. There was a statistically demonstrable advantage for cyclophosphamide over hydroxyurea and a marginal advantage over methyl-chloroethyl-cyclohexy-nitrosourea in survival experience.

The over-all 3, 5 and 10-year survival rate for 87 patients with non-seminomatous germ cell tumors of the testis undergoing retroperitoneal lymphadenectomy was 90.5 per cent. Of the 72 patients receiving no form of therapy other than retroperitoneal lymphadenectomy after operative removal of the testicular tumor the 5-year survival rate was 90.8 per cent. The 5-year survival rates for these 72 patients, calculated according to the histologic characteristics of the primary tumor, were 74.4 per cent for 18 patients with embryonal carcinoma, 93.0 per cent for 36 patients with teratocarcinoma and 100 per cent for 18 patients with teratoma. Although no advantage could be demonstrated for bilateral lymphadenectomy as opposed to unilateral dissection, it is concluded that a modified bilateral dissection should be reserved only for tumors on the left side.

An unusual case of synchronous development of renal adenocarcinoma and transitional cell carcinoma of the renal pelvis in the same kidney is presented.

The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma.

We treated 100 patients with metastatic renal cell carcinoma by angioinfarction of the primary tumor followed by radical nephrectomy. Of the patients 88 also received postoperative parenteral progesterones. We achieved an over-all response rate of 28 per cent (complete regression of all metastatic lesions in 7 patients, regression greater than 50 per cent in 8 and stabilization for at least 1 year in 13). Patients with parenchymal pulmonary metastases only have the best survival rate (64 per cent at 1 year) and are most likely to benefit from angioinfarction and nephrectomy. The presence of hilar or mediastinal adenopathy, pleural effusion or nonpulmonary metastases confers a worse prognosis. These patients do not appear to survive longer with preoperative angioinfarction than if treated by nephrectomy alone. Our data demonstrate that it is critically important to stratify patients by site and volume of disease when results are reported and compared for any patient undergoing treatment for metastatic renal cell carcinoma.

The clinical and morphologic features of 18 patients with paratesticular rhabdomyosarcoma are reviewed. Although medical attention was sought frequently within 2 months the lesion was mistaken initially for other more common scrotal conditions in more than a third of the patients, delaying a correct diagnosis for 3 weeks to 4 months. Half of the patients had retroperitoneal lymph node metastases. However, with multimodal therapy 61 per cent remain free of disease at a median of 6 years from diagnosis.

To study the site of origin of epithelial regeneration in the urinary bladder after surgical denudation, we completely obliterated the bladder mucosa in 17 dogs, using the neodymium:YAG laser. Bladder-mapping studies showed that the regenerating cells arose from the epithelium of the terminal ureters and urethra. Experimental construction of isolated bladder pouches confirmed these findings and demonstrated that urine flow was not essential for reepithelialization. These results are relevant to the treatment of patients with multifocal carcinoma in situ of the bladder. Although the entire bladder can be denuded successfully, the studies demonstrate that the procedure might fail if the sources of epithelial regrowth, the distal ureters and urethra, contain untreated carcinoma in situ.