Definitive therapy for prostate carcinoma: Mayo Clinic results at 15 years after treatment.

Data on long-term follow-up for definitive therapy of prostate cancer are limited, especially for radiation therapy. Either surgery or radiation was used in 322 patients for treatment with curative intent, and follow-up was for a minimum of 15 years. Overall survival was nearly identical to that in age-matched cohort. 5-, 10-, and 15-year recurrence-free survival rates were 77%, 63% and 53%, respectively. Grade and stage were significant prognostic factors for both recurrence and survival. More than 60% of the initial failures were local, and more than 25% of the failures occurred after 10 years. Radiation therapy was used in 137 patients with clinically staged disease. Radical retropubic prostatectomy and perineal prostatectomy were performed in 133 and 44 patients, respectively. In this group, pathological staging was used. Survival rates for surgically treated patients were better than those in the cohort population. In conclusion, overall long-term follow-up demonstrates that definitive treatment does not have an adverse effect on survival from prostate cancer. Local recurrence is a frequent cause of failure. Caution must be used in interpreting any prostate study with less than 10 years of follow-up, because 25% to 50% of the failures occur after that time.

Treatment options for patients with stage D1 (T0-3,N1-2,M0) adenocarcinoma of prostate.

Three hundred six patients with adenocarcinoma of the prostate underwent pelvic lymphadenectomy and had Stage D1 (T0-3,N1-2,M0) disease; 171 patients underwent radical retropubic prostatectomy with or without immediate adjuvant therapy (hormonal or radiation or both) or conservative (hormonal or radiation or both) treatment alone (n = 135). Follow-up was one-half to eighteen and one-half years (mean, 5 yrs). Immediate adjuvant orchiectomy significantly (P = 0.01) improved survival (87.4% at 10 years) and nonprogression rates for patients who underwent radical prostatectomy, but not for those who had lymphadenectomy. Overall patient survival was significantly better (P = 0.005) after prostatectomy than lymphadenectomy. Residual disease (n = 43) in patients who underwent prostatectomy and received adjuvant treatment (orchiectomy or radiation or both) did not affect disease outcome. Bilateral pelvic lymphadenectomy and radical prostatectomy with immediate adjuvant orchiectomy provided survival comparable to the expected survival; conservative treatment alone was associated with rapid disease progression and poor survival and significantly (P = 0.02) higher local morbidity.

Bilateral pelvic lymphadenectomy and radical prostatectomy for clinical stage C prostatic cancer: role of adjuvant treatment for residual cancer and in disease progression.

A total of 101 patients with limited but unequivocal clinical stage C adenocarcinoma of the prostate underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. At operation 49 patients had pathological stage C and 52 had stage D1 disease. Followup ranged from 0.5 to 17 years (mean 4.9 years). The 5 and 10-year observed survival rates for patients with stages C and D1 disease were similar to the expected survival. Sixteen patients had residual cancer postoperatively but only 2 had local progression: 1 had received no adjuvant therapy, and 1 had received diethylstilbestrol and radiation. None of the others, having received adjuvant radiation and/or orchiectomy, suffered local recurrence. Over-all, local progression occurred in 17 patients, only 4 of whom had received adjuvant treatment initially (diethylstilbestrol, 1 also received radiation). Local progression occurred in 13 of 47 patients (28 per cent) without adjuvant treatment. Thus, in all patients immediate adjuvant bilateral orchiectomy or radiation (except for 1 patient) prevented local progression. In patients with pathological stage D1 disease bilateral orchiectomy significantly reduced disease progression (p less than 0.0001). Therefore, limited clinical stage C adenocarcinoma of the prostate can be successfully treated surgically (with low morbidity) when supplemented with appropriate immediate adjuvant treatment.

Testicular seminoma metastatic to the prostate.

A 43-year-old man had clinically manifest prostatic involvement by a metastatic testicular seminoma. The signs, symptoms, diagnosis and treatment of this entity, as well as a hypothesis regarding its development, are discussed.

Evaluation of the prostate by magnetic resonance imaging.

Forty-seven male patients with suspected prostatic disease underwent magnetic resonance imaging (MRI) of the pelvis on a Picker resistive magnet operating at 0.15 T; 33 had histologically proved adenocarcinoma, 12 benign prostatic hypertrophy, 1 a transitional cell carcinoma, and 1 a seminoma. Eleven normal subjects also were included in the study. The study attempted to (1) define the MRI characteristics of the normal prostate, benign prostatic hypertrophy, and prostatic adenocarcinoma, (2) evaluate various pulse sequences in imaging the prostate, and (3) compare MRI findings with clinical, pathologic, and computed tomography results. Various pulse sequences, including inversion recovery and spin-echo with short and long TE and TR, were used. MRI was sensitive in detecting intracapsular and extracapsular prostatic disease. The finding of inhomogeneous signal texture throughout the gland was a sensitive but nonspecific finding for adenocarcinoma. A focal nodule with prolonged T1 and T2 relaxation times was the most specific MRI finding for adenocarcinoma. Extracapsular spread of neoplasm was often demonstrated, and because of its superior soft-tissue contrast ability, MRI was more accurate than computed tomography in delineating extracapsular extension.

Review of Mayo Clinic experience with carcinoma in situ.

Experience with carcinoma in situ (CIS) of the urinary bladder during a twenty-year period at the Mayo Clinic is reviewed. The most important clinical clues for diagnosis of this disease continue to be irritative bladder symptoms in the absence of infection in elderly men and a history of transurethral resection of the prostate. The most reliable method of diagnosis is urinary cytology. When not modified by treatment, CIS is the precursor of most invasive cancers, originating probably from an area of atypical hyperplasia into CIS and, finally, into invasion. Among patients considered to have CIS who undergo cystectomy, 34 per cent may already have microinvasion. CIS has the potential to involve the entire urothelium. Prudence should guide the use of intravesical chemotherapy (mitomycin or thiotepa or doxorubicin), which may control the disease for extended periods in many patients. If primary treatment fails, immediate second-line treatment should include BCG or hematoporphyrin derivative (HpD) phototherapy or both. If such therapy fails, delay of radical cystectomy seems inadvisable. Monitoring of the prostatic urethra during intravesical treatment is mandatory; a radical surgical procedure should be performed once the prostatic urethra is involved. Results of treatment for secondary prostatic and upper urinary tract cancer are dismal. Conversely, secondary urethral disease, although it occurs frequently beyond five years, may be associated with a good prognosis.

Pelvic lymphadenectomy and radical cystectomy for transitional cell carcinoma of the bladder with pelvic nodal disease.

Past and present methods of treatment for patients with stage D1 (T1-4 N+ MO) transitional cell cancer of the urinary bladder have proved to be largely ineffective. This report on 57 patients with stage D1 disease confirms this impression and demonstrates that radical operation alone is associated with a 5-year survival rate of only 10%. Survival is related to tumour grade and to the number of pelvic lymph nodes involved; furthermore, complete lymphadenectomy may contribute to improved patient survival. Effective treatment programmes for stage D1 bladder cancer are lacking and efforts should be directed toward developing treatment protocols that combine radical cystectomy and meticulous pelvic node dissection with an effective adjuvant systemic treatment programme.

Acute toxicity and preliminary therapeutic results of pelvic lymphadenectomy combined with transperineal interstitial implantation of 192IR and external beam radiotherapy for locally advanced prostate cancer.

We have developed a combined modality approach for treatment of locally advanced prostate cancer consisting of: surgical staging with lymphadenectomy; transperineal placement of afterloading needles for a course of 192Ir brachytherapy; and a course of moderate-dose external beam irradiation to tight prostatic fields. The flexibility of the treatment permits adaptation of the dose to any tumor configuration. A total of 23 patients have been treated to date; 18 are available for treatment review and 14 for acute toxicity analysis. Significant morbidity has occurred in only 2 patients, 1 with a pelvic hematoma and 1 with hematoma in the wound. Local tumor response has been excellent in all but 1 patient. A good degree of symptomatic improvement was observed at the three-month follow-up. This approach appears to be safe and effective at this time. A brief review of the technique and the rationale for its use are also presented.

Androgen receptor binding activity in human prostate cancer.

Androgen binding (cytosol and nucleus) was measured in tissue obtained from 223 untreated patients with proven prostate cancer (199 primary tumor, 24 malignant lymph nodes), 19 patients with hormone refractory cancer, and 46 patients with benign prostatic hyperplasia (BPH). The mean binding in both the cytosol and nucleus was significantly higher for patients with cancer than for those with BPH. Binding appeared to correlate with tumor stage. Androgen binding in malignant nodes can differ from that in the primary tissue and can vary from node to node in the same patient. Results obtained from an assay using a single saturating concentration of R1881 correlated well with those calculated from a full six-point Scatchard analysis when an adequate amount (500 mg) of tissue was available. However, binding results obtained from a single-point analysis performed on needle biopsy specimens (about 50 mg) obtained before complete surgical removal of the prostate correlated poorly with those derived from a full six-point analysis performed on tissue (500-1000 mg) removed from the center of the malignancy. Androgen binding in nuclear extracts of histologically benign tissue adjacent to the malignancy was significantly higher than in nuclear extracts of BPH tissue. Cytosolic androgen binding in tissue removed from patients who were refractory to hormonal therapy was higher than in tissue from untreated cancer patients. The binding of estradiol by extracts of benign and malignant prostate tissue was low or absent and, thus, did not appear to be a significant phenomenon.

Bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for Stage C adenocarcinoma of prostate.

A series of 105 patients with surgical Stage C adenocarcinoma of the prostate underwent pelvic lymphadenectomy and radical retropubic prostatectomy and were followed up from one and one-half to fifteen years; 33 (31%) of the 105 had clinical Stage C disease. Of the 105 patients, 92 were at risk for greater than or equal to two years, 42 for greater than or equal to five years, and 12 for greater than or equal to ten years. Survival and disease progression were related to tumor grade (Mayo grades 1 through 4) and tumor bulk (less than 3, 3 to 10, greater than 10 cm3) but not to seminal vesicle involvement. Twenty-seven patients received adjuvant treatment (orchiectomy, DES, radiation, or combinations of these); it was administered to patients with higher tumor grades, larger tumor bulk, and/or residual cancer. Overall actuarial survival at five and ten years was 85 per cent and 72 per cent, respectively; five-year nonprogression rate was 64 per cent. Local recurrence was noted in only 8 patients (7.6%). Radical surgical treatment for nonbulky Stage C disease of the prostate is associated with favorable survival results and good local control. Adjuvant treatment may favorably affect disease outcome. Clinical seminal vesicle involvement with negative urethrocystoscopy should not necessarily deter the surgeon from planning radical prostatectomy. Prospective adjuvant treatment protocols need to be developed to identify the value of adjuvant hormone and/or radiation therapy.

Carcinoma in situ of the urinary tract.

The identification and description of carcinoma in situ by pathologists and the recognition of its clinical features and diagnostic clues by clinicians represent a significant advancement in the struggle to conquer invasive epithelial cancer in recent times. The authors discuss symptoms, diagnosis, pathologic features, and treatment.

Radical excision of adenocarcinoma of prostate with pelvic lymph node involvement: surgical gesture or curative procedure.

From 1967 to 1981, 100 patients with carcinoma of the prostate and positive lymph node involvement underwent pelvic lymphadenectomy and radical retropubic prostatectomy. At surgery, adjuvant treatment consisted of none in 52, orchiectomy in 37, and other (radiation and/or diethylstilbestrol) in 11 subjects. Of all the variables assessed (tumor bulk, grade, seminal vesicle involvement, number of positive nodes, and adjuvant treatment), only the number of positive nodes was found to affect survival and progression when no adjuvant treatment was given. Progression was significantly limited by orchiectomy, which had an equalizing effect on all patients with positive nodes, possibly independent of the number of positive nodes.

Epidemic of pulmonary blastomycosis (Namekagon fever) in Wisconsin canoeists.

Epidemics of pulmonary blastomycosis have rarely been reported. The following epidemic occurred in a Minnesota family and several of their acquaintances after a canoeing trip in northwestern Wisconsin. The common exposure area was most likely a campsite, located along the upper reaches of the Namekagon River. The Namekagon River Valley is a known endemic area of Namekagon fever (blastomycosis) in dogs. Approximately one month after returning home, five of the eight members of the group had positive direct microscopic examinations and cultures of Blastomyces dermatitidis from their sputa, as well as abnormalities on their chest roentgenograms. Among these five patients, four were symptomatic, with fever, cough, and pleuritic chest pain. Of the three others, one had pleuritic chest pain with a transient lung infiltrate, the second was asymptomatic with a transient lung infiltrate, and the third was asymptomatic with a normal chest roentgenogram. Results of acute serologic tests (complement fixation and immunodiffusion) were negative in all five patients evaluated. None of the patients received antifungal therapy. Follow-up five years after the epidemic revealed that all eight were in excellent health, and none had evidence of continuing pulmonary or extrapulmonary disease.

Observations on surgical management of carcinoma of prostate with limited nodal metastases.

One hundred patients with surgical Stage D1 (TXN + M0) adenocarcinoma of the prostate underwent pelvic lymphadenectomy and radical retropubic prostatectomy and were followed up for one-half to fifteen and one-half years. Forty-eight patients received "adjuvant" hormonal or radiation (or both) treatment; all patients were treated ("delayed") hormonally on disease progression, when this treatment had not been administered initially. Tumor grade (Mayo 1 through 4), tumor bulk (measured in cm3), or seminal vesicle involvement alone and when considered with number of positive nodes was not related to survival or disease progression. Only number of positive nodes and bilateral orchiectomy as "adjuvant" treatment affected survival and progression. For the 52 patients without "adjuvant" orchiectomy, the overall five-year rate for nonprogression was only 18.5 per cent, and the five-year rates for nonprogression were, respectively, 26, 0, and 0 per cent when 1, 2, and greater than or equal to 3 positive nodes were considered. However, for the 37 patients who received "adjuvant" orchiectomy, the overall five-year rate for nonprogression was 95 per cent, and the five-year rates for nonprogression were, respectively, 100, 100, and 80 per cent when 1, 2, and greater than or equal to 3 positive nodes were considered. Prostatic cancer with positive pelvic lymph nodes treated by pelvic lymphadenectomy and radical retropubic prostatectomy alone leads to rapid disease progression. "Adjuvant" bilateral orchiectomy is associated with projected five- and ten-year survival rates of 94 per cent and 80 per cent, respectively. Recommendation of other treatment modalities for patients with Stage D1 cancer of the prostate should be considered with reference to the results presented herein.

Bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for adenocarcinoma confined to the prostate.

A total of 519 patients with clinical stage B disease underwent radical prostatectomy from 1966 to 1981: 65 (12.5 per cent) had pathologic stage D1, 72 (14.0 per cent) pathologic stage C and 382 (73.5 per cent) pathologic stage B disease. Of the 519 patients 320 with pathologic stage B1 (239) or B2 (81) adenocarcinoma of the prostate and no prior hormonal or radiation therapy underwent complete pelvic lymphadenectomy and radical retropubic prostatectomy. Stage, grade and size of tumor were associated significantly with interval to disease progression but not with survival. The probable explanation for this observation is that only 2 per cent of 186 patients who were followed for 5 years and 2 per cent of 46 who were followed for 10 years died of prostatic carcinoma within these intervals. The over-all survival of patients who had intracapsular prostatic carcinoma was not different from that of an age-matched surgical control group (men undergoing total hip arthroplasty during the same interval). These observations suggest that although morbidity from alternative therapies may vary no other treatment modality offers survival superior to that observed for pelvic lymphadenectomy and radical retropubic prostatectomy in patients with pathologic intracapsular prostatic cancer.

Treatment of transitional cell carcinoma of the bladder with hematoporphyrin derivative phototherapy.

The demonstration that intravenously administered hematoporphyrin derivative concentrates preferentially in dysplastic and neoplastic transitional cells in the human bladder prompted a trial of hematoporphyrin derivative phototherapy in patients with transitional cell cancer of the bladder. A dose of 2.5 mg. per kg. was given intravenously 3 to 48 hours before treatment with light of a wavelength of 630 nm. from an argon ion pumped dye laser. Total light dose approximated 150 joules per cm.2. Four patients with resistant carcinoma in situ have been treated and all have had disappearance of the tumors proved by biopsy. Although there are many technical problems we believe that hematoporphyrin derivative phototherapy holds promise as an effective treatment modality, primarily for patients with resistant, recurrent in situ transitional cell carcinoma of the bladder.

Hormonal treatment at time of radical retropubic prostatectomy for stage D1 prostate cancer.

We classified 70 prostatic cancers as stage D1 at the time of pelvic lymphadenectomy and radical prostatectomy. For retrospective analysis after 1 to 14 years of followup, the patients were divided into 32 in whom endocrine therapy had been given immediately postoperatively and 38 in whom it had not. These 2 groups did not differ substantially in patient age, Gleason grade, pathologic stage, tumor volume or seminal vesicle involvement. The mean number of involved nodes per patient was higher in the hormone-treated group (2.9 versus 1.8). According to Kaplan-Meier projections 88 per cent of such patients without hormonal treatment will have progression within 5 years, compared to only 14 per cent of those given hormonal treatment immediately. However, projected survival differed little between the groups, most likely since 17 of the 18 patients with progression in the nontreated group were given hormonal treatment as soon as progression was substantiated. Definitive assessment of the impact of the timing of endocrine therapy on patient survival and time to disease progression awaits a randomized trial with long-term followup.