Prostate-specific antigen nadir: the optimum level after irradiation for prostate cancer.

PURPOSE: The prostate-specific antigen (PSA) nadir that reflects potential cure of prostate cancer by irradiation has not been established. This report attempts to demonstrate the PSA nadir goal for radiotherapy. MATERIALS AND METHODS: From January 1984 through April 1994, 536 stage T1T2NO prostate cancer patients were treated with radioactive iodine 125 (125I) prostate implants followed by external-beam radiation. All were staged node-negative: 68% by pelvic node dissection and the remainder by computed tomographic (CT) scan. The mean pretreatment PSA level was 12.4 ng/mL (median, 8.4 ng/mL; range, 0.3 to 188 ng/mL). The median follow-up duration is 40 months (range, 12 to 138). An increasing posttreatment PSA level defined recurrence. RESULTS: Patients who achieved a PSA nadir < or = 0.5 ng/mL had a 95% (+/- 4%) 5-year and an 84% (+/- 12%) 10-year disease-free survival rate, compared with a 5-year disease-free survival rate of 29% (+/- 30%) for those who reached a nadir of 0.6 to 1.0 ng/mL (P = .0001). All patients with a nadir greater than 1.0 ng/mL ultimately failed. Eighty percent of all 536 patients are projected to achieve a nadir < or = 0.5 ng/mL and 90% of patients who achieve this PSA level do so within 48 months of treatment (median, 18 months). Compared with pretreatment PSA level and histologic grade, the PSA nadir is the most significant factor associated with disease-free survival. CONCLUSION: For most patients to be successfully treated for prostate cancer with radiotherapy, at least with this combination technique, the PSA nadir should become undetectable (< or = 0.5 ng/mL), similar to that after radical prostatectomy. A PSA nadir of < or = 0.5 ng/mL after radiotherapy for prostate cancer may be used as a reasonable indicator of 10-year disease-free survival.

The PSA nadir that indicates potential cure after radiotherapy for prostate cancer.

OBJECTIVES: The prostate-specific antigen nadir that indicates potential cure by radiotherapy has never been established. We determined this nadir level and used it to define precisely disease freedom after radiotherapy. METHODS: Combination radioactive 125I prostate implant followed by external-beam radiation was administered to 660 men with clinical Stage T1T2N0 prostate cancer. The average pretreatment prostate-specific antigen level (Tandem R Assay) was 11.7 ng/mL (median 8.0 ng/mL, range 0.3 to 188 ng/mL). To analyze these data, recurrence was defined as a prostate-specific antigen level rising above whatever nadir was achieved. The median follow-up is 42 months (range 12 to 150 months). RESULTS: Eighty-one percent of all men are calculated to achieve a prostate-specific antigen nadir of 0.5 ng/mL or less and to have a 5- and 10-year disease-free survival rate of 93% and 83%, respectively, as compared with a 5-year disease-free survival rate of 26% for those achieving a nadir of 0.6 to 1.0 ng/mL--a significant difference (P = 0.0001). All men with a nadir greater than 1.0 ng/mL ultimately failed treatment. Of 201 men with a minimum 5-year follow-up, 143 are disease-free and 140 (98%) achieved and maintained a nadir of 0.5 ng/mL or less. CONCLUSIONS: For possible cure of prostate cancer with radiotherapy, a prostate-specific antigen nadir of 0.5 ng/mL or less should be achieved. With this nadir level, disease freedom after irradiation is defined as achievement and maintenance of a nadir of 0.5 ng/mL or less. A nadir greater than 0.5 ng/mL or subsequent increase above 0.5 ng/mL is defined as irradiation treatment failure. This definition may help resolve the controversy about the potential for cure of prostate cancer by irradiation.

Fibrin glue for partial nephrectomy.

Fibrin glue, a mixture of concentrated autologous fibrinogen and bovine-derived thrombin, was used to achieve hemostasis during 7 partial nephrectomies. After transected vessels were suture ligated, topically applied fibrin glue filled all renal defects with an adherent clot that resulted in immediate hemostasis. There was no case of delayed hematoma or abscess formation, and no complications were referrable to the use of fibrin glue. Although fibrin glue is no substitute for early vascular control and careful surgical technique, its ability to stop venous oozing from the cut surface of renal parenchymal tissue dramatically facilitates hemostatic control.

Stage B (P2/3A/N0) transitional cell carcinoma of bladder highly curable by radical cystectomy.

Seventy-one patients with pathologic Stage B (P2/3a/N0) transitional cell carcinoma (TCC) of the bladder underwent radical cystectomy alone without preoperative radiotherapy or perioperative chemotherapy between 1983 and 1987 and have been followed a median of fifty months. The five-year actuarial survival and disease-free survival rates were 82 percent and 77 percent, respectively, and only 13 patients (18%) have relapsed. Histologic parameters were evaluated as to prognostic impact; none correlated with disease-free survival rates although the presence of vessel involvement portended a worse disease-free survival rate (68% versus 80%). During this same period, an additional 15 patients underwent radical cystectomy for pathologic Stage B disease but received adjuvant chemotherapy on the basis of vessel invasion. Their disease-free survival rate at five years was 80 percent, comparable to the disease-free survival rate for patients with vessel invasion treated by surgery alone (68%). Although the role of systemic chemotherapy in the management of invasive bladder cancer remains under investigation, it would appear that patients with Stage B TCC are best treated with radical cystectomy alone. Continued analysis of modern surgical results grouped by current pathologic staging criteria is needed to identify patients who have a relatively low risk of relapse and thus little need for additional therapeutic intervention. These results demonstrate that Stage P2/3a/N0 TCC of the bladder is highly curable by surgery.

Indications for urethrectomy in an era of continent urinary diversion.

Interest in performing a continent urinary diversion and in preserving sexual potency after radical cystectomy for transitional cell carcinoma of the bladder has emphasized the need to identify accurately those men who are at high risk for urethral recurrences. We reviewed the records of 200 men who underwent radical cystectomy between 1969 and 1976. In 76 men urethrectomy and cystectomy were combined. Of these patients 6 had known urethral tumors and the incidence of unsuspected urethral malignancy was 2.9%. A total of 124 men had initial cystectomy only and were monitored up to 16 years (mean 67 months). Of these patients 6 (4.8%) underwent subsequent urethrectomy for malignant disease 6 to 40 months (median 23.5 months) after cystoprostatectomy. This group included 1 of 69 patients (1.5%) who presented with a solitary tumor not encroaching on the bladder neck, 1 of 22 (4.5%) with either carcinoma in situ or multifocal tumors not involving the prostate and none of the 9 with tumor at the bladder neck alone, which suggests that these patients may be satisfactory candidates for continent urinary diversion and may avoid the added risk to potency associated with urethrectomy. However, urethral recurrences were found in 4 of 24 patients (17%) who presented with disease extending into the prostate, including 3 of 10 (30%) with stromal invasion. These results emphasize the importance of assessing the prostatic urethra and ducts carefully before deciding to eliminate urethrectomy.

Simultaneous irradiation for prostate cancer: intermediate results with modern techniques.

PURPOSE: In this study of men with early stage prostate cancer we evaluated treatment outcome after modern simultaneous irradiation, comprising transperineal implantation followed by external beam radiation. Disease-free survival rates were calculated according to an undetectable prostate specific antigen (PSA) nadir. MATERIALS AND METHODS: From 1992 to 1996, 689 men with clinical stage T1-T2, N0, Nx prostate cancer were treated with ultrasound guided transperineal 125iodine seed implantation followed 3 weeks later by external beam radiation. Disease-free status was defined as the achievement and maintenance of a PSA nadir of 0.2 ng./ml. or less. Median followup was 4 years (range 3 to 7). None of these men received neoadjuvant or adjuvant hormonal therapy. RESULTS: Overall 5-year disease-free survival was 88%. The 5-year rate according to PSA 4.0 ng./ml. or less, 4.1 to 10.0, 10.1 to 20.0 and greater than 20.0 was 94%, 93%, 75% and 69%, respectively. Multivariate analysis revealed that pretreatment PSA was the strongest indicator of subsequent disease-free status in regard to Gleason score or clinical stage. CONCLUSIONS: Intermediate treatment outcome analysis of modern simultaneous radiation supports the principles of radiation dose intensification for intracapsular disease plus the treatment of potential microscopic capsular penetration.

Familial renal cell carcinoma: hereditary or coincidental?

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.

Simultaneous radiotherapy for prostate cancer: 125I prostate implant followed by external-beam radiation.

PURPOSE: Using a rigorous prostate-specific antigen definition of disease-freedom, the 10-year disease-free survival rates after simultaneous radiation of prostate cancer are presented. PATIENTS AND MATERIALS: From January 1984 through December 1996, 1020 men with clinical stage T1T2N0 prostate cancer were treated by simultaneous radiation: radioactive 125I prostate implantation followed by external-beam radiation. The median pretreatment prostate-specific antigen was 7.5 ng/mL (range, 0.2-188 ng/mL). Implantation was performed by both the retropubic and the transperineal technique, always followed by external-beam radiation. None received hormone treatment. Disease freedom is defined as achieving and maintaining a posttreatment prostate-specific antigen of < or = 0.5 ng/mL. The median follow-up is 3 years (range, 1-14 years). RESULTS: The overall 5- and 10-year disease-free survival rates are 79% and 72%, respectively, after which a plateau is reached. At 5 years posttreatment, significantly better disease-free survival results are documented with simultaneous radiation by the ultrasound technique (92%) compared with the retropubic implant technique (73%). On multivariate analysis, pretreatment prostate-specific antigen is the most significant factor associated with disease-free survival, followed by implant technique. DISCUSSION: The 10-year disease-free survival rate after simultaneous radiation is comparable to the 10-year results after radical prostatectomy. Disease freedom is defined by the same prostate-specific antigen criteria used for surgery. A plateau in the disease-free curve suggests cure. Of equal importance, the information described in this report should form only a baseline relative to future results as men treated with simultaneous radiation using the transperineal implant technique reach longer follow-up.

Prostate specific antigen bounce after radioactive seed implantation followed by external beam radiation for prostate cancer.

PURPOSE: Prostate specific antigen (PSA) may temporarily increase following radiotherapy for prostate cancer without signaling cancer recurrence. We describe this phenomenon which is called PSA bounce. MATERIALS AND METHODS: From 1984 to 1995, 779 stage T1T2N0 cancer cases were treated with simultaneous radiotherapy with a 125iodine prostate implant followed by external beam radiation. Median pretreatment PSA was 7.7 ng./ml. (range 0.3 to 188). PSA bounce was defined as an increase of 0.1 ng./ml. or greater above the preceding PSA level after simultaneous radiation followed by a subsequent decrease below that level. Disease-free status was defined as the ability to achieve and maintain posttreatment PSA 0.2 ng./ml. or less. RESULTS: PSA bounce was observed in 35% of men (273 of 779). Median time to PSA bounce was 18 months from the time of implant and 92% of bounces were observed within 36 months. Median pre-bounce PSA was 0.7 ng/ml. (range 0.1 to 8.9) and median bounce height (increase above the pre-bounce level) was 0.4 ng./ml. (range 0.1 to 15.8). No distinguishing characteristics were observed between men with PSA bounce and those with cancer recurrence, and bounce had no prognostic significance relative to recurrence. CONCLUSIONS: PSA bounce is common following seed implantation for prostate cancer. It produces anxiety in men previously treated for prostate cancer and confounds the diagnosis of recurrence.

Prostate specific antigen nadir achieved by men apparently cured of prostate cancer by radiotherapy.

PURPOSE: The role of prostate specific antigen (PSA) nadir in the definition of disease freedom after radiotherapy of prostate cancer is controversial. We evaluate post-irradiation PSA nadir in men apparently cured of this disease. MATERIALS AND METHODS: From 1984 to 1993, 354 men with clinical stage T1T2N0 prostate cancer were treated with radioactive 125iodine prostate implant followed by external beam radiation. Median pretreatment PSA was 8.4 ng/ml (range 0.3 to 188). Of these men 250 are disease-free and median pretreatment PSA was 6.5 ng/ml (range 0.3 to 123). Treatment failure is defined as 3 consecutive PSA increases above nadir. Median followup is 7 years (range 5 to 14 years) for the 250 disease-free men and 6 years (range 0.5 to 14) for all 354 men. RESULTS: PSA nadir 0.5 ng/ml or less was achieved by 98% of all disease-free men (244 of 250) with minimum 5-year followup, including 87% (217) who achieved nadir 0.2 ng/ml or less. All 27 disease-free men with minimum 10-year followup had a PSA nadir of 0.5 ng/ml or less. PSA nadir significantly correlated with disease-free survival by receiver operator characteristics curve analysis (0.93 area under the curve) in all 354 men. CONCLUSIONS: PSA nadir is the fundamental measurement that determines possible cure after radiotherapy. Except for perhaps rare occasions, men must at least achieve a nadir of 0.5 ng/ml. or less to be cured of prostate cancer by irradiation. However, the prognostic value of this nadir level depends on most men achieving a nadir of 0.2 ng/ml or less. Disease freedom for radiotherapy, defined as achievement and maintenance of PSA nadir 0.5 ng/ml or less, is reasonable.

Post-treatment PSA < or = 0.2 ng/mL defines disease freedom after radiotherapy for prostate cancer using modern techniques.

OBJECTIVES: The prostate-specific antigen (PSA) definition of disease freedom after radiotherapy for prostate cancer is still in dispute. This report focuses on the PSA nadir achieved in men treated by modern radiotherapy techniques. METHODS: From 1984 to 1994, 489 consecutive men with clinical Stage T1 -T2 prostate cancer were treated by simultaneous radiation: prostate iodine-125 implant followed by external beam radiation. A transperineal implant was performed on 143 men with Stage T1-T2NX, the focus of this study; 346 men with Stage T1-T2N0 had a retropubic implant. The median pretreatment PSA was 8.3 ng/mL (range 0.3 to 188). A rising PSA was defined as one that rose on three consecutive occasions above whatever nadir was achieved. A minimum 5-year follow-up (range 5 to 15) was reached by 453 men. RESULTS: After a minimum 5-year follow-up, 336 men had a nonrising PSA, and of this group, 107 had undergone simultaneous radiation by the transperineal implant technique. A PSA nadir of 0.2 ng/mL or less was achieved by 97% of the transperineally implanted men, and 3% had a nadir of 0.3 to 1.0 ng/mL. Of the 489 men, those who had a nadir of 0.2 ng/mL or less had a 92% nonrising PSA rate (P = 0.001) 10 years after treatment compared with a 41% rate for men who had a nadir of 0.3 to 1.0 ng/mL. All men whose nadir was greater than 1.0 ng/mL had recurrence. The median time to achieve the PSA nadir of 0.2 ng/mL was 27 months (range 3 to 102). CONCLUSIONS: Primarily on the basis of the results from men treated with simultaneous radiation using the transperineal technique, the definition of disease freedom for radiotherapy should be men who achieve and maintain a PSA nadir of 0.2 ng/mL or less.