Long-term Outcomes and Patterns of Failure Following Trimodality Treatment With Bladder Preservation for Invasive Bladder Cancer.

OBJECTIVE: To report long-term results on survival, toxicity, and patterns of failure of 3 different organ-sparing strategies for patients with muscle invasive bladder cancer. MATERIALS AND METHODS: This is a monoinstitutional prospective analysis of 3 consecutive bladder-sparing protocols combining maximal transurethral resection of bladder tumor (mTURBT), radiotherapy (RT), and cisplatin-based chemotherapy. Protocol 1 consisted of neoadjuvant methotrexate-cisplatin-vinblastine followed by endoscopic re-evaluation and consolidative RT 60 Gy in complete responders. Protocol 2 involved altered-fractionation RT 64.8 Gy and concurrent weekly cisplatin with re-evaluation after 40.8 Gy. Protocol 3 consisted of RT 64.8 Gy with concomitant weekly cisplatin. Nonresponders underwent radical cystectomy. Probabilities for overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier product limited estimates. A Cox regression multivariate analysis was performed to detect potential risk factors for OS, CSS, and MFS. RESULTS: The 10-year bladder preservation rate was 79%. The 10-year OS, CSS, and MFS rates were 43.2%, 76.3% and 79.2%, respectively. There was no statistically significant difference in OS between the different treatment protocols. On multivariate analysis, mTURBT of the bladder and the complete response after induction therapy were independent correlates of improved OS and of MFS. The development of invasive bladder recurrence was independently associated with worse CSS and MFS. CONCLUSION: Ten-year results indicate that bladder-sparing treatment is a successful approach for muscle invasive bladder cancer in selected patients. The mTURBT of the bladder tumor and complete response after induction therapy remain the most relevant predictive factors.

Marcadores moleculares como factores predictivos de fracaso bioquímico en el cáncer de próstata después de tratamiento radical / Molecular markers as predictive factors biochemical failure after radical treatment of prostate cancer

En la actualidad, los nomogramas basados en los factores pronósticos "convencionales", como el grado de Gleason, el estadio tumoral y el PSA al diagnóstico, siguen siendo las mejores herramientas para predecir el pronóstico del cáncer de próstata (CP). Sin embargo, en la última década, se ha producido un notable avance biotecnológico que ha supuesto una fuente esencial para la investigación de nuevos marcadores moleculares de valor pronóstico y predictivo, tanto en tejido como en suero. En esta revisión, se repasarán los principales biomarcadores, tanto convencionales como más noveles, con principal atención a aquellos implicados en la respuesta a los tratamientos (radioterapia, cirugía u hormonoterapia). Aunque todavía no están preparados para su empleo rutinario en la practica clínica, la combinación de estos biomarcadores, con los marcadores tradicionales y las variables terapéuticas, nos permitirá seleccionar a los pacientes para ensayos con nuevas terapias dirigidas que en un futuro no muy lejano sean la base del tratamiento individualizado(AU)

Clinical nomograms based on Gleason grade, tumor stage, and serum PSA are still the best predictors of prostate cancer (PC) outcome. The biotechnological advancements achieved in the last decade represent a remarkable source for new prognostic and predictive tissue and serum molecular biomarkers. In this review, we will summarize conventional PC prognostic biomarkers and focus on novel identified biomarkers for PC early diagnosis and progression that might be used in the future. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pre-treatment and treatment-related variables and will improve our ability to predict outcome and select the optimal treatment(AU)

Long-term results after high-dose radiotherapy and adjuvant hormones in prostate cancer: how curable is high-risk disease?

PURPOSE: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. METHODS AND MATERIALS: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). RESULTS: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score>7 (p=0.001), pretreatment prostate-specific antigen (PSA) level>20 ng/mL (p=0.037), higher radiation dose (p=0.005), and the use of adjuvant LTAD vs. STAD (p=0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose>78 Gy was 97%. CONCLUSIONS: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum>7 and pretreatment PSA level>20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with addition of novel agents.

Statistical analysis of dose-volume and dose-wall histograms for rectal toxicity following 3D-CRT in prostate cancer.

The purpose of this paper is to determine the correlation between dose-volume histogram (DVH) and dose wall-histogram (DWH) in the evaluation of rectal complications for prostate cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). A retrospective analysis of DVHs and DWHs of a subset of 25 prostate cancer patients treated with 3D-CRT was performed. For every patient the rectum and the rectal wall (inner and outer surface) were contoured. Median ICRU radiation dose of 79.4 Gy was administered. Correlation between DVHs and DWHs parameters was investigated by the nonparametric Spearman test and by linear regression analysis. The results showed a statistically significant linear correlation between pairs of DVH and DWH dosimetric parameters with Spearman correlation values (S) bigger than 0.8, with p values better than 0.0005 (two-sided) when the emptied rectum is considered. The variation of S and linear fit slope values [b(1)] showed a very similar functional shape with a minimum at 91% ICRU dose [S =0.83, b(1)=0.65]. The present study confirms a high correlation (>80%) between DVH and DWH of the rectum following 3D-CRT for prostate cancer. The derived advantage is that the contouring of inner surface of rectum could be obviated in almost 90% of patients when performing predictive models for rectal complications based on dosimetric variables under the standard treatment conditions specified in this study.

Impact of mean rectal dose on late rectal bleeding after conformal radiotherapy for prostate cancer: dose-volume effect.

PURPOSE: To identify the clinical and dosimetric factors predictive of a greater risk of Grade 2 or worse late rectal bleeding in patients with localized prostate cancer treated with three-dimensional conformal radiotherapy in a prospective dose-escalation study. METHODS AND MATERIALS: We performed a retrospective analysis of the clinical records and dose-volume histograms of 107 patients with Stage T1c-T3 prostate cancer treated at our institution with three-dimensional conformal radiotherapy who had a minimal follow-up of 1 year. Of the 107 patients, 21 were treated at dose level 1 (70.0 Gy), 57 at dose level 2 (72.0 Gy), and 29 at dose level 3 (75.6 Gy). The mean International Commission on Radiation Units and Measurements reference dose was 76.5 Gy (range, 69.8-82.6 Gy). RESULTS: The 4-year actuarial incidence of Grade 2 or worse late rectal bleeding was 7.7% +/- 2.5%. The results of the multivariate analysis indicated that the mean rectal dose (rectal D(mean); p = 0.003) and the percentage of rectum receiving >60 Gy (Vr(60); p = 0.002) correlated with Grade 2 or worse rectal bleeding. The receiver operating characteristic curve analysis showed that this logistic regression model using both Vr(60) and rectal D(mean) had good reliability to predict the risk of late rectal bleeding. The area under the curve for Vr(60) and rectal D(mean) was 0.889 and 0.892, respectively. CONCLUSION: The results of the present study provide clear evidence of a dose-volume effect and the importance of intermediate doses (60.0 Gy) on the risk of rectal bleeding at this prescription dose level. On the basis of these results, new constraints have been implemented in our institution to keep the risk of developing Grade 2 rectal bleeding reasonably low (rectal D(mean) 50.0 Gy and Vr(60) 42%).