Selective bladder preservation for muscle-invasive transitional cell carcinoma of the urinary bladder.

Invasive transitional cell carcinoma (TCC) of the urinary bladder is traditionally treated with radical cystectomy. This approach results in great morbidity and lifestyle changes, and approximately half of the patients treated in this way will experience recurrent TCC despite surgery. An alternative approach using selective bladder-preservation techniques incorporates transurethral resection of bladder tumours, radiation therapy, and chemotherapy. Over the past 20 years, international experience has demonstrated that this approach is feasible, safe, and well tolerated. Furthermore, the long-term outcomes of overall survival and disease-free survival compare favourably with the outcomes from radical cystectomy. The most important predictor of response is stage, with significantly higher long-term survival in patients with T2 disease. Another important positive predictor of complete response to therapy is the ability of the urologic oncologist to remove all visible tumour through a transurethral approach prior to initiation of radiation therapy. A negative predictive factor is the presence of hydronephrosis, and age and gender do not affect disease-free survival. The majority of patients who enjoy long-term survival do so with an intact native bladder. Quality of life studies have demonstrated that the retained bladder functions well in nearly all of these patients. Selective bladder preservation will not entirely take the place of radical cystectomy, but should be offered as an important alternative to patients newly diagnosed with muscle-invasive TCC.

Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer.

OBJECTIVES: To evaluate the outcomes of patients with muscle-invasive Stage T2-4a bladder carcinoma managed by transurethral surgery and concurrent chemoradiation. METHODS: A total of 190 patients were treated on institutional prospective protocols using concurrent cisplatin-containing chemotherapy and radiotherapy after rigorous transurethral resection of the bladder tumor. Patients were re-evaluated by repeated biopsy and urine cytologic analysis after 40 Gy, with the initial tumor response guiding subsequent therapy. One hundred twenty-one patients with a complete response by cytologic and histologic examination and those medically unfit for cystectomy received boost chemoradiation to 64 to 65 Gy. Those patients without a complete response were advised to undergo radical cystectomy. A total of 66 patients (35%) ultimately underwent radical cystectomy; 41 for less than a complete response and an additional 25 for recurrent invasive tumors. The median follow-up was 6.7 years for all surviving patients. RESULTS: The 5 and 10-year actuarial overall survival rate was 54% and 36%, respectively (Stage T2, 62% and 41%; Stage T3-T4a, 47% and 31%, respectively). The 5 and 10-year disease-specific survival rate was 63% and 59% (Stage T2, 74% and 66%; Stage T3-T4a, 53% and 52%), respectively. The 5 and 10-year disease-specific survival rate for patients with an intact bladder was 46% and 45% (Stage T2, 57% and 50%; Stage T3-T4a, 35% and 34%), respectively. The pelvic failure rate was 8.4%. No patient required cystectomy because of bladder morbidity. CONCLUSIONS: The 10-year overall survival and disease-specific survival rates are comparable with the results reported for contemporary radical cystectomy for patients of similar clinical and pathologic stage. One third of patients treated on protocol with the goal of bladder sparing ultimately required a cystectomy. A trimodality approach with bladder preservation based on the initial tumor response is, therefore, safe, with most long-term survivors retaining functional bladders.

Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder.

OBJECTIVES: Although radical cystectomy remains the standard of care for invasive bladder cancer in the United States, many groups are exploring the use of trimodality therapy using transurethral resection of the bladder tumor, radiation, and chemotherapy in an attempt to spare patients the need for cystectomy. As transitional cell carcinoma often arises from a urothelial field change, there is concern that the retained bladder is at risk of subsequent superficial (Ta, T1, Tis) tumors, some of which may have lethal potential. This study reports the outcomes of those patients with superficial relapse of transitional cell carcinoma after trimodality therapy. METHODS: One hundred ninety patients were treated using a series of trimodality therapy protocols between 1986 and 1998. All patients received induction chemotherapy and radiation and were selected for bladder preservation on the basis of a cytologic and histologic complete response. One hundred twenty-one patients had a complete response and formed the subjects of this study. RESULTS: With a median follow-up of 6.7 years for patients still alive, 32 experienced a superficial relapse (26%). The median time to this failure was 2.1 years. Sixty percent of the superficial failures were carcinoma in situ (Tis) and 67% arose at the site of the original invasive tumor. The risk of superficial failure was higher among those who had Tis associated with their original muscle-invasive tumor. Twenty-seven of these 32 cases were managed conservatively with transurethral resection and intravesical therapy. The irradiated bladder tolerated this therapy well and only 3 patients required treatment breaks. The 5 and 8-year survival was comparable for those who experienced superficial failure (68% and 54%, respectively) and those who had no failure at all (n = 74, 69% and 61%, respectively). However, a substantially lower chance of being alive with the native bladder owing to the need for late salvage cystectomies (61% versus 34%) was found. Cystectomy became necessary in 31% (10 of 32) either because of additional superficial recurrence (n = 7) or progression to invasive disease (n = 3). CONCLUSIONS: A trimodality approach to transitional cell bladder cancer mandates lifelong cystoscopic surveillance. Although most completely responding patients retain their bladders free from invasive relapse, one quarter will develop superficial disease. This may be managed in the standard fashion with transurethral resection of the bladder tumor and intravesical therapies but carries an additional risk that late cystectomy will be required.

The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response.

PURPOSE: To assess the safety, tolerance, and efficacy of transurethral surgery plus concomitant cisplatin, 5-fluorouracil (5-FU), and radiation therapy in conjunction with selective bladder preservation in patients with muscle-invading bladder cancer. Patients and Methods. Thirty-four eligible patients with clinical stage T2-T4a, Nx M0 bladder cancer without hydronephrosis were entered into a protocol aimed at selective bladder preservation. Treatment began with as complete a transurethral resection as possible followed by induction chemoradiation. This consisted of cisplatin 15 mg/m(2) i.v. and 5-fluorouracil (5-FU) 400 mg/m(2) i.v. in the mornings on d 1, 2, 3, 15, 16, and 17. On d 1, 3, 15, and 17, radiation was given immediately following the chemotherapy using twice-a-day 3 Gy per fraction cores to the pelvis for a total radiation dose of 24 Gy. Response was evaluated by cystoscopy, cytology, and rebiopsy four weeks later. Patients with a complete response received consolidation therapy with the same drugs and doses on d 1, 2, 3, 15, 16, and 17 combined with twice-daily radiation therapy to the bladder and bladder tumor volume of 2.5 Gy per fraction for a total consolidation dose of 20 Gy and a total induction plus consolidation dose to the bladder and bladder tumor of 44 Gy. Patients who did not achieve a complete response were advised to undergo prompt cystectomy, as were those with a subsequent invasive recurrence. The median follow up is 29 months. RESULTS: Of the 34 eligible patients, 26 had a visibly complete transurethral resection. One patient did not complete induction treatment due to acute hematologic toxicity. After induction treatment, 22 (67%) of the 33 patients had no tumor detectable on urine cytology or rebiopsy. Of the 11 patients who still had detectable tumor, six underwent radical cystectomy and five underwent consolidation chemoradiation (one because of refusal to have the recommended cystectomy and four because the treating institutions erroneously assigned them to receive consolidation chemoradiation rather than cystectomy). No patient has required a cystectomy for radiation toxicity. Six patients have died of bladder cancer. The actuarial overall survival at three years is 83%. The probability of surviving with an intact bladder is 66% at three years. A total of seven patients (21%) developed grade 3 or grade 4 hematologic toxicity in conjunction with this treatment. CONCLUSION: This aggressive protocol comprising local surgery plus concurrent 5-FU, cisplatin, and high-dose hypofractionated radiation has been associated with moderately severe hematologic toxicity. Longer follow-up will be necessary to assess efficacy. Both the 67% complete response rate to induction therapy and the 66% three-year survival with an intact bladder are encouraging.

An update of combined modality therapy for patients with muscle invading bladder cancer using selective bladder preservation or cystectomy.

PURPOSE: We update the results of tri-modality treatment for patients with muscle invading bladder tumors with selection for bladder preservation based on tumor response to induction therapy. MATERIAL AND METHODS: We reviewed the literature on modern tri-modality bladder preserving approaches using transurethral resection, radiation and concurrent chemotherapy followed by either bladder conservation with careful surveillance for complete responding patients or prompt cystectomy in those whose tumors persist after induction therapy. RESULTS: The published experiences from 3 centers and 2 prospective trials done by the Radiation Therapy Oncology Group were evaluated for 5-year overall survival of patients selected for bladder preservation or prompt cystectomy (49 to 63%) and for those with a conserved bladder (38 to 43%). The overall 5-year survival rates were comparable to other series of immediate cystectomy based approaches in patients of similar age and presenting with tumors of similar clinical stage. Of patients treated with the bladder preserving approach 20 to 30% cured of muscle invading cancer will subsequently have a new superficial tumor. The superficial tumors have responded well to intravesical drug therapy. Modern bladder preserving treatments usually result in a well functioning bladder without incontinence or significant hematuria. However, concurrent systemic chemotherapy and radiation have the potential for acute morbidity. Presently the ideal candidate for bladder preservation has primary clinical stage T2 tumor, no associated ureteral obstruction, visibly complete transurethral resection and complete response after induction chemoradiation based on endoscopic evaluation including re-biopsy and cytology. CONCLUSIONS: It is recommended that tri-modality treatment be administered by dedicated multimodality teams. In this country this approach to treatment is available at many of the institutions participating in the Radiation Therapy Oncology Group study. This treatment may be considered a reasonable alternative in patients who are deemed medically unfit for cystectomy and for those who are seeking an alternative to radical cystectomy.

Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03.

PURPOSE: To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS: One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS: Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION: Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.

A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer.

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.

Invasive bladder cancer: treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation.

PURPOSE: Combined modality therapy has become the standard oncologic approach to achieve organ preservation in many malignancies. METHODS AND MATERIALS: Although radical cystectomy has been considered as standard treatment for invasive bladder carcinoma in the United States, good results have been recently reported from several centers using multimodality treatment, particularly in patients with clinical T2 and T3a disease who do not have a ureter obstructed by tumor. RESULTS: The components of the combined treatment are usually transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation therapy. Following an induction course of therapy a histologic response is evaluated by cystoscopy and rebiopsy. Clinical "complete responders" (tumor site rebiopsy negative and urine cytology with no tumor cells present) continue with a consolidation course of concurrent chemotherapy and radiation. Those patients not achieving a clinical complete response are recommended to have an immediate cystectomy. Individually the local monotherapies of radiation, TURBT, or multidrug chemotherapy each achieve a local control rate of the primary tumor of from 20 to 40%. When these are combined, clinical complete response rates of from 65 to 80% can be achieved. Seventy-five to 85% of the clinical complete responders will remain with bladders free of recurrence of an invasive tumor. CONCLUSIONS: Bladder conservation trials using combined modality treatment approaches with selection for organ conservation by response of the tumor to initial treatment report overall 5-year survival rates of approximately 50%, and a 40-45% 5-year survival rate with the bladder intact. These modern multimodality bladder conservation approaches offer survival rates similar to radical cystectomy for patients of similar clinical stage and age. Bladder-conserving therapy should be offered to patients with invasive bladder carcinoma as a realistic alternative to radical cystectomy by experienced multimodality teams of urologic oncologists.

Treatment strategies using transurethral surgery, chemotherapy, and radiation therapy with selection that safely allows bladder conservation for invasive bladder cancer.

Combined modality therapy with the goal of effecting cure and achieving organ preservation has become the standard oncological approach in many malignancies. Although radical cystectomy has been considered the standard treatment for invasive carcinoma of the bladder, equivalent results have been achieved using combined modality treatment in selected patients, particularly those with T2 and T3a disease without obstructed ureters. Effective combined modality treatment consists of three treatment modalities: (1) transurethral resection of the bladder tumor (TURBT), followed by concurrent (2) chemotherapy, and (3) radiation. Following induction therapy, histologic response is evaluated by cystoscopy and biopsy. Clinical complete responders continue with concurrent chemotherapy and irradiation. Those patients not achieving a clinical complete response are advised to undergo cystectomy. Individually the local monotherapies of radiation, TURBT, or systemic chemotherapy each achieve a local control rate of 20% to 40%. When they are combined, complete response rates of 70-80% are achieved and 85% of these will remain free of invasive recurrence in the bladder. Bladder preservation trials using combined modality treatment approaches with selection for organ conservation by response to initial treatment report an overall 5-year survival rate of approximately 50%, and they have achieved a 40% to 45% 5-year survival rate with the bladder intact. Modern multi-modality bladder preservation approaches offer survival rates similar to radical cystectomy, for patients of similar clinical stage and age, and an improved quality of life by allowing a majority of patients to retain their own fully functional bladder. Bladder conservation therapy may be offered to selected patients with bladder cancer as one alternative to radical cystectomy, and its use should be by experienced multi-modality teams of urologic oncologists.

The case for radiotherapy with or without chemotherapy in high-risk superficial and muscle-invading bladder cancer.

The standard treatment for superficial high-grade bladder cancer is transurethral resection with or without subsequent intravesical therapy. Although a few series have reported good local control rates for T1 tumors, using either external beam irradiation or brachytherapy, this does not represent the standard of care in the United States. External beam radiation may be attempted in patients whose tumors cannot be resected transurethrally and who refuse cystectomy. The case for radiotherapy with or without chemotherapy is far stronger in muscle-invading cancers. Overall survival rates around 50% have been reported in larger series from a number of major centers. Most of these 5-year survivors retain their native bladders. The bladder morbidity of such an approach is very low. There are several studies currently active to determine the most appropriate sequence and combination of drugs and radiation.

Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer.

PURPOSE: We performed a retrospective analysis to assess the durability of benefit derived from irradiation after prostatectomy for pT3N0 disease, and the possibility of cure. METHODS AND MATERIALS: We studied 88 patients who were irradiated after prostatectomy and had available prostate specific antigen (PSA) data, no known nodal or metastatic disease, no hormonal treatment, and follow-up of at least 12 months from surgery. Forty patients received adjuvant therapy for a high risk of local failure with undetectable PSA. Forty-eight patients received salvage therapy for elevated PSA levels. Mean follow up was 44 months from date of surgery and 31 months from irradiation. Biochemical failure was strictly defined as a confirmed rise in PSA of >10%, or as the ability to detect a previously undetectable PSA value. RESULTS: After salvage irradiation, 69% of patients attained an undetectable PSA. Eighty-eight percent of adjuvant patients were biochemically and clinically free of disease (bNED) at 3 years from prostatectomy. Sixty-eight percent of those receiving salvage irradiation were bNED 3 years after surgery. On univariate analysis, treatment group (adjuvant or salvage), pre-operative PSA, and the status of seminal vesicles were significant prognostic factors. The extent of PSA elevation in the salvage group was also significant. We did not demonstrate a significant difference between those salvage patients referred for persistently elevated PSA as compared to those with a late rise in PSA. On multivariate analysis, the only significant predictor of outcome was treatment group, with adjuvant irradiation having better outcome than salvage. CONCLUSION: More than two-thirds of this group of patients remain biochemically disease free at 3 years following irradiation, attesting to a number of potential cures. For patients with stage pT3N0 prostate cancer following radical prostatectomy, our data support the use of either routine postoperative adjuvant irradiation or close PSA follow-up with early salvage treatment.

Bladder preservation by combined modality therapy for invasive bladder cancer.

PURPOSE: To update the efficacy of a selective multimodality bladder-preserving approach by transurethral resection (TURBT), systemic chemotherapy, and radiation therapy. PATIENTS AND METHODS: From 1986 through 1993, 106 patients with muscle-invading clinical stage T2 to T4a,Nx,M0 bladder cancer were treated with induction by maximal TURBT and two cycles of chemotherapy (methotrexate, cisplatin, vinblastine [MCV]) followed by 39.6-Gy pelvic irradiation with concomitant cisplatin. Patients with a negative postinduction therapy tumor site biopsy and cytology (a T0 response, 70 patients) plus those with less than a T0 response but medically unfit for cystectomy (six patients), received consolidative chemoradiation to a total of 64.8 Gy. Surgical candidates with less than a T0 response (13 patients) and patients who could not tolerate the chemoradiation (six patients) went to immediate cystectomy. The median follow-up duration is 4.4 years. RESULTS: The 5-year actuarial overall survival and disease-specific survival rates of all patients are 52% and 60%, respectively. For clinical stage T2 patients, the actuarial overall survival rate is 63%, and for T3-4, 45%. Thirty-six patients (34%) underwent cystectomy, all with evidence of tumor activity, including 17 with an invasive recurrence. The 5-year overall survival rate with an intact functioning bladder is 43%. Among 76 patients who completed bladder-preserving therapy, the 5-year rate of freedom from an invasive bladder relapse is 79%. No patient required cystectomy for treatment-related bladder morbidity. CONCLUSION: Combined modality therapy with TURBT, chemotherapy, radiation, and selection for organ-conservation by response has a 52% overall survival rate. This result is similar to cystectomy-based studies for patients of similar age and clinical stages. The majority of the long-term survivors retain fully functional bladders.

Opportunities with combined modality therapy for selective organ preservation in muscle-invasive bladder cancer.

Combined-modality therapy for organ preservation represents an appropriate alternative to radical surgery in the management of several malignant diseases. The standard therapy for muscle-invasive bladder cancer in the United States has been radical cystectomy. Although the sequelae of radical surgery have been ameliorated somewhat by techniques for the construction of orthotopic bladders, the ideal therapy should both cure the patient of cancer and maintain a functioning natural bladder. Years of experience in Europe and Canada with bladder preservation using radiation therapy are documented. Advances in transurethral surgery technique and in the combination of radiation and chemotherapy have led to safe and effective regimens for patients with bladder cancer. Several recent trials with combined-modality therapy have established this treatment as a viable alternative to radical cystectomy in selected patients.

Conservative surgery, patient selection, and chemoradiation as organ-preserving treatment for muscle-invading bladder cancer.

Multimodality organ-sparing treatment has, during the last decade, become the standard of care for many common malignancies. In appropriately selected patients with muscle-invading bladder cancer, bladder-preserving treatment combining surgical transurethral resection (TUR) with chemoradiation therapy offers a chance for long-term cure and survival equal to cystectomy, while also affording a 60% to 70% chance of maintaining a normally functioning bladder. Selection criteria helpful in determining appropriate patients for bladder preservation include such variables as small tumor size, that a visibly complete TUR is possible, the absence of hydronephrosis and that a complete response (CR) to induction chemoradiotherapy was achieved. Selecting patients based on response to induction therapy allows for prompt cystectomy if residual disease is found or for prompt consolidation chemoradiotherapy if a CR with induction therapy is achieved. Bladder-preserving treatment usually results in a normally functioning bladder without incontinence or hematuria for stage T2 and T3a patients. Stage T3b-T4 patients are locally controlled less frequently using these techniques. However, no data exist to suggest that patients with more advanced disease are in any way disadvantaged by preoperative chemoradiotherapy as an attempt at bladder conservation. Patients require close urological surveillance as do any patients with superficial bladder cancer who are being treated conservatively. As studies addressing the possibility of organ preservation continue to show positive results, more patients will become informed about and will be offered selective bladder-sparing approaches as one-treatment option.

Combined modality treatment with selective bladder conservation for invasive bladder cancer: long-term tolerance in the female patient.

PURPOSE: To assess the physical, psychological, social, and organ-specific long-term treatment sequelae occurring in women with muscle-invading bladder carcinoma treated with combined modality therapy that allowed for bladder conservation in 67% of patients. PATIENTS AND METHODS: Patients with muscle-invading (T2-4a,Nx,M0) bladder cancer were treated with maximal transurethral resection followed by induction chemoradiotherapy (cisplatin x 2 plus 40 Gy pelvic irradiation or the same preceded by 2 cycles of methotrexate, cisplatin, and vinblastine) between the years 1986 and 1994. Women who had a complete response and all those who were not candidates for cystectomy received consolidation therapy of additional cisplatin and tumor boost to 64.8 Gy. Women who were incomplete responders and those who developed recurrent invasive tumor underwent immediate radical cystectomy. Forty-two women were treated with this approach, 21 of whom (median age, 69 years; median follow-up time, 56 months) were available for and underwent a structured interview of treatment and health-related issues using a quantitative symptom score. RESULTS: All 21 patients have full urinary continence and no dysuria. Nineteen report unchanged or improved bladder capacity and function. No patient reported loss of bowel continence. Of the five women who were sexually active, two report an increase in intercourse frequency and one noted a decrease. There is no decrease in intercourse satisfaction or orgasm, and no dyspareunia or vaginal bleeding was noted. Eleven patients reported high levels of anxiety related to their bladder cancer before treatment. This was significantly reduced or absent in 9 of 11 after treatment. Actuarial overall survival for all 42 women was 58% at 5 years. Actuarial overall survival with an intact bladder was 47% at 5 years. DISCUSSION: This study shows that overall survival is high when chemoradiation and transurethral resection are used in potential bladder-sparing protocols for muscle-invading transitional cell carcinoma of the bladder in women. Furthermore, 67% of the women, including most long-term survivors, retain their bladders. The functional quality of the conserved organ, the rectum, and the vagina, as reported by the patients, was excellent.

Time to second prostate-specific antigen failure is a surrogate endpoint for prostate cancer death in a prospective trial of therapy for localized disease.

OBJECTIVES: The most relevant endpoint in comparing the efficacy of curative therapies for prostate cancer is cancer-specific death. Prospective trials need to mature for a least a decade to yield meaningful cancer death data due to the long natural history of the disease amd the use of salvage androgen suppression. This delay may be long enough that the tested treatments are outdated by the time of reporting; thus, there is a need for reliable early surrogate endpoints for cancer survival. METHODS: This report evaluates 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer. Patients were accrued between 1982 and 1992 and received radical irradiation to either a standard dose of 67.2 Gy or a higher dose of 75.6 Gy. Median follow-up was 5.4 years. A total 76 men have received androgen suppression or orchiectomy for salvage following relapse. Of this group, 35 experienced a second relapse heralded by a rise in the serum prostate-specific antigen (PSA). RESULTS: The median survival from the time of second biochemical relapse (defined as a progression with a rise in serum PSA more than 10% above the nadir after androgen suppression) was 27 months. Kaplan-Meier analysis projected a 0% survival for this group at 4 years. All those dying after second biochemical failure died of the prostate cancer. CONCLUSIONS: Second PSA failure (or PSA progression on hormonal therapy) has potential as a surrogate for impending cancer death and its use as an endpoint in prospective studies could allow earlier reporting by 2 to 4 years.

Selective bladder preservation by combination treatment of invasive bladder cancer.

BACKGROUND: For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. We sought to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured. METHODS: We enrolled 53 consecutive patients with muscle-invading bladder cancer (stages T2 through T4, NXM0) in a trial of transurethral surgery, combination chemotherapy, and irradiation (4000 cGy) with concurrent cisplatin administration. Urologic evaluation of the tumor response directed further therapy: radical cystectomy in the 8 patients who had incomplete responses, additional chemotherapy and radiotherapy (6480 cGy) in the 34 patients who had complete responses or who were unsuited for cystectomy, and alternative care in the 11 patients who could not tolerate either irradiation or chemotherapy. RESULTS: After a median follow-up of 48 months, 24 of the 53 patients (45 percent) were alive and free of detectable tumor. In 31 patients (58 percent) the bladder was free of invasive tumor and functioning well, even though in 9 (17 percent) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 28 patients who had complete responses after initial treatment, 89 percent had functioning tumor-free bladders. CONCLUSIONS: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial that included a group for simultaneous comparison would be required to produce definitive results.

Natural history of superficial bladder cancer. Prognostic features and long-term disease course.

Superficial bladder cancer or, more accurately, stages Ta, T1, and Tis encompass a spectrum that ranges from innocuous to life-threatening lesions. There is growing evidence that Ta grade 1 tumors rarely become invasive; although when there is associated carcinoma in situ or severe dysplasia, the risk of invasiveness increases. Carcinoma in situ is treacherous, with unpredictable behavior. Predictors of recurrence and progression are beginning to be identified for the various superficial tumors.