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.

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.

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.

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.

Laser induced autofluorescence diagnosis of bladder cancer.

PURPOSE: We assessed the ability of laser induced autofluorescence to differentiate malignant from nonmalignant bladder lesions. MATERIALS AND METHODS: We studied 53 patients with bladder cancer undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder. Tissue fluorescence was excited by 337 nm. light pulses (nitrogen laser). One fiber was used for transmission of the excitation and emission (fluorescence) light. An optical multichannel analyzer system was used to record fluorescence spectra of the sites of interest. RESULTS: We analyzed the fluorescence spectra of 114 bladder areas (1 carcinoma in situ as well as 28 malignant, 35 inflammatory, 7 dysplastic, 1 squamous metaplastic and 42 normal areas). These lesions included 44 difficult to diagnose suspicious tumors (11 malignant and 33 nonmalignant). We developed an algorithm that used the I385:I455 nm. fluorescence ratio to distinguish malignant from nonmalignant lesions, including inflammatory areas. By analyzing the data on all 114 lesions, we noted the sensitivity, specificity, and positive and negative predictive values of this method for differentiating malignant from nonmalignant bladder lesions to be 97, 98, 93 and 99%, respectively. CONCLUSIONS: Under excitation with 337 nm. light a clear differentiation between malignant and nonmalignant bladder tissues can be made using the I385:I455 nm. autofluorescence ratio.

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.

Use of PSA nadir to predict subsequent biochemical outcome following external beam radiation therapy for T1-2 adenocarcinoma of the prostate.

PURPOSE: This study assessed the ability of nadir prostate-specific antigen (PSA) to act as an early surrogate for subsequent freedom from biochemical failure following radiation therapy for T1-2 prostatic adenocarcinoma. METHODS AND MATERIALS: A retrospective analysis was performed on the biochemical outcome of 314 consecutive men with T1-2 disease treated by conventional external beam radiation at the Massachusetts General Hospital. Minimum follow up was 2 years, and failure was defined as three successive rises in serum PSA of greater than 10%. Kaplan-Meier actuarial analysis of outcome was employed. RESULTS: The overall 5-year freedom from biochemical progression was 63%. For those who achieved a PSA nadir of < or = 0.5 ng/ml (n = 123) it was 90%, for 0.6-1.0 ng/ml (n = 103) it was 55%, and for > 1.0 ng/ml (n = 88) it was 34%. Multivariate analysis showed an undetectable PSA nadir to be independent of Gleason grade and initial PSA in predicting subsequent outcome (P < 0.05). The likelihood of achieving an undetectable PSA nadir correlated strongly with the pretreatment value: 74% if this was below 4 ng/ml; 42% for those between 4.1 and 10 ng/ml; and 32% for those above 10 ng/ml. CONCLUSION: A PSA nadir of < or = 0.5 ng/ml represents an early endpoint strongly predictive of a favorable outcome following radiation therapy which may be used for the rapid assessment of new radiation strategies.

The management of spermatic cord sarcoma.

BACKGROUND: Between April 1963 and July 1991, 18 patients were treated for spermatic cord sarcoma. The histologic subtype distribution was: 7 leiomyosarcoma, 7 liposarcoma, 2 malignant fibrous histiocytoma, and 1 mesothelioma. METHODS: All patients underwent surgical resection: 16 radical orchiectomy and local excision. Nine were treated with orchiectomy alone, and 9 received adjuvant radiation. The radiation fields encompassed the ipsilateral iliac and inguinal lymph nodes, vas deferens, and hemiscrotum in 7 patients, and iliac and inguinal lymph nodes in 2 patients. RESULTS: The actuarial 5 and 8-year disease free survivals for the 18 patients were 77% and 58%, with an overall survival of 78% and 70%, respectively. The 5 and 8-year locoregional control rates were 82% and 61%. Five of 9 patients treated with surgery alone developed locoregional recurrence while none of the nine who had adjuvant radiation relapsed. The median follow-up for the irradiated group, however, was shorter (123 vs 63 months) and staging studies more complete. These potential biases are discussed. CONCLUSION: In this series, relapse was common after orchiectomy alone. Adjuvant radiation therapy may reduce the incidence of locoregional failure.

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.

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.

Adjuvant irradiation after radical prostatectomy for adenocarcinoma of prostate: analysis of freedom from PSA failure.

A total of 84 consecutive men with extracapsular disease after radical prostatectomy who received postoperative irradiation and no adjuvant endocrine therapy were analyzed. Failure was defined as the development of clinical disease recurrence either locally or at a distant site, the development of detectable prostate-specific antigen (PSA) when postoperatively it had been undetectable, or any rise in PSA when postoperatively it still had been detectable. Sixteen of the 84 men had nodal disease. Overall, five-year actuarial freedom from relapse was 60 percent. For node-negative men, it was 64 percent and for node-positive men 43 percent. For the 68 men with pathologic Stage T3N0 disease, five-year freedom from relapse was 73 percent when seminal vesicles were negative and 43 percent when involved. Tumor grade also predicted the likelihood of recurrence. In a multivariate analysis the time interval from surgery to radiation and the level of postoperative PSA (detectable versus undetectable) did not influence the likelihood of relapse nor the median time to relapse. Fourteen separate patients treated with radiation alone for palpable tumor recurrence were also analyzed. Fewer than 40 percent were disease-free only two years after irradiation. We conclude that when treatment failure is defined in biochemical as well as clinical terms postoperative irradiation reduces the rate of relapse at five years relative to recently reported series in which adjuvant irradiation was not given. The additional morbidity is low. Whether or not this will translate into an overall cause-specific survival gain is currently unclear.

Deoxyribonucleic acid flow cytometry in invasive bladder carcinoma: a possible predictor for successful bladder preservation following transurethral surgery and chemotherapy-radiotherapy.

Tumor deoxyribonucleic acid (DNA) ploidy was evaluated as an objective parameter that may correlate better with the responsiveness of bladder cancer to chemotherapy plus radiotherapy than do clinical features or histopathological subtypes. A total of 40 patients with localized muscle-invading bladder cancer (clinical stages T2 to T4) underwent prospective treatment on a potential bladder preserving protocol. Tumors of 37 of the 40 patients were analyzed by DNA flow cytometry of multiple paraffin embedded specimens. Transurethral resection, neoadjuvant chemotherapy and 40 Gy. radiotherapy plus cisplatin were followed by urological reevaluation of the tumor (a complete response required a negative biopsy and a negative urine cytology study). A total of 7 noncomplete response patients underwent immediate radical cystectomy whereas the full bladder sparing treatment (radiotherapy to 64.80 Gy. plus cisplatin) was given to 23 complete response patients and 7 noncomplete response patients who were unsuited for surgery. Of the tumors 22 (59%) were purely aneuploid and 10 (27%) were purely diploid. Five tumors contained aneuploid and diploid patterns in different tumor specimens (partly diploid). Current status with a 30-month median followup in surviving patients includes an 82% overall survival rate in the aneuploid group versus 47% in the diploid/partly diploid group. Of all the patients 68% are free of invasive tumor: 82% in the aneuploid group versus 47% in the diploid/partly diploid group. By multivariate analysis pure aneuploidy was significantly (p = 0.05) correlated with freedom from invasive tumor in the bladder (either as persistence or as recurrence) and approached significance (p = 0.08) in correlation with overall patient survival. A longer observation time will be required to confirm this unexpectedly good outcome for patients with pure aneuploid tumors. We hypothesize that pretreatment DNA ploidy status may become a clinically useful prognostic factor in selecting patients for successful treatment with transurethral surgery and neoadjuvant chemotherapy plus radiotherapy.