RACE AS AN INDEPENDENT PREDICTOR OF OUTCOME AFTER TREATMENT FOR LOCALIZED PROSTATE CANCER

PURPOSE: We analyze the outcome after prostatectomy or radiotherapy for localized prostate cancer with respect to race. MATERIALS AND METHODS: A total of 2,219 consecutive patients with prostate cancer were treated with radiotherapy (1,183) or radical prostatectomy (1,036) between June 1986 and June 1998. Initial prostate specific antigen (PSA) and biopsy Gleason scores were available in all cases. Androgen deprivation was used in 22% of men (492). Of the patients 86% (1,901) were white, including Hispanic and Asian, and 14% (318) were black. The outcomes of interest were biochemical relapse-free survival, clinical relapse-free survival and overall survival. Median followup was 24 months (range 2 to 140). RESULTS: There was no difference in the incidence of familial prostate cancer, patient age at presentation, clinical stage or biopsy Gleason scores between black and white men. However, black men had higher initial PSA levels (median 13.3 versus 8.6 for white men, p<0.001). The 5-year biochemical relapse-free survival rate was 59% for the entire group, 54% (95% confidence interval 44 to 63) for black men and 61% (95% confidence interval 57 to 65) for white men (p = 0.11). Multivariate analysis was performed for the variables of age, race, family history of prostate cancer (brother or father), initial PSA, biopsy Gleason sum, clinical T stage, treatment modality and androgen deprivation. Familial prostate cancer (p = 0.001), higher T stage (p<0.001), higher initial PSA (p<0.001), higher biopsy Gleason score (p<0.001) and use of androgen deprivation (p = 0.001) were independent predictors of biochemical failure and all other factors, including race, were not (p = 0.46). The projected 10-year clinical relapse-free survival rate was 74% for the entire group, and was identical for black and white men (p = 0.77). The projected 10-year overall survival rate for black and white men was 92 and 79%, respectively (p = 0.62). CONCLUSIONS: We have demonstrated a statistically nonsignificant trend for higher biochemical failure rates in black men presenting with localized prostate cancer. This trend could be due to the higher pretreatment PSA levels in black patients. Treatment recommendations should not differ with respect to race.     

Salvage radiotherapy for isolated prostate specific antigen increase after radical prostatectomy: evaluation of prognostic factors and creation of a prognostic scoring system

PURPOSE: This study was performed to evaluate the results and prognostic factors associated with radiotherapy for a detectable serum prostate specific antigen level after radical prostatectomy. MATERIALS AND METHODS: From July 1987 through July 2003, 368 patients received radiotherapy for a detectable prostate specific antigen level (biochemical relapse) as the sole evidence of recurrence after radical prostatectomy for node negative prostate cancer. Estimated survival and relapse-free probabilities were obtained via Kaplan-Meier estimation. Associations of patient factors with survival and biochemical relapse were investigated using Cox proportional hazards models. RESULTS: With a median followup of 5 years the 5 and 8-year freedom from biochemical relapse were an estimated 46% (95% CI 41%-53%) and 35% (95% CI 29%-43%) while survival was 92% (95% CI 89%-95%) and 80% (95% CI 74%-87%), respectively. Patient and treatment variables showing evidence of association with biochemical relapse on multivariate analysis included pathological stage T3a or less vs T3b (seminal vesicle involvement, p = 0.029), pathological Gleason score 7 or less vs 8 or greater (p <0.001) and pre-radiotherapy prostate specific antigen (p <0.001). Four biochemical failure risk groups were created by assigning seminal vesicle involvement, Gleason score and pre-radiotherapy prostate specific antigen each a score of 0 to 2. These individual scores were summed. The freedom from biochemical failure at 5 years for each risk group was 0 to 1-69%, 2-53%, 3-26% and 4 to 5-6%. CONCLUSIONS: The presence of seminal vesicle involvement and high Gleason score in the radical prostatectomy specimen are inherent predictors of adverse outcome. Early referral for salvage radiotherapy can decrease subsequent biochemical relapse.     

Comparison of surgery alone with surgery and adjuvant radiotherapy for pT3N0 prostate cancer

OBJECTIVE: To compare the outcome between patients with pT3N0 adenocarcinoma of the prostate treated with radical prostatectomy (RP) and those receiving RP followed by a planned course of postoperative radiation therapy (RT). PATIENTS AND METHODS: During a period of 22 years 622 patients with pT3N0 prostate cancer were treated in one medical centre by RP. Of these, 199 (32%) were treated with surgery alone while 423 (68%) received planned postoperative pelvic RT (median 48 Gy). Patients were selected for RT by having a higher incidence of adverse prognostic factors than those undergoing RP alone. These prognostic factors included pathological stage (P = 0.001) preoperative prostate specific antigen (PSA) level (P < 0.001) and Gleason score (P = 0.18). The patients' median age was 66 years; the median follow-up was 6.1 years for all patients, 7 years for RP + RT and 5 years for the RP-alone. RESULTS: The 5- and 10-year actuarial survival was 92% and 73%, respectively, for RP + RT patients, and nearly identical for those in the RP-alone group (P = 0.73). The 5- and 10-year disease-free survival (DFS; PSA < 0.05 ng/mL) was 69% and 51%, respectively, for the former, and 71% and 60%, respectively, for the latter group. There was no significant difference in DFS between the treatment groups by pathological stage and Gleason score (P = 0.77). Likewise, there was no significant difference in mean and median time to relapse. A preoperative PSA level of < 10 vs 10-25 vs > 25 ng/mL did not influence overall survival but a PSA of > 25 ng/mL was predictive of DFS (P = 0.02). In a multivariate analysis the Gleason score was the most important predictor for overall survival and DFS (P < 0.001), while pathological stage was predictive of clinical recurrence and DFS (P < 0.001). After controlling for pathological stage and Gleason score, RP + RT patients were predicted to recur at 92% of the rate of RP-alone patients (P = 0.65). In all, 43 (10%) patients developed a clinical recurrence in the RP + RT group, including 30 (7%) patients with distant metastases alone, 13 (3%) with local recurrence, with an additional 88 (21%) who had PSA recurrence (PSA > 0.05 ng/mL). This compared with 13 (6.5%) patients with clinical recurrence, including seven (3.5%) with local recurrence and 23 (11.6%) with PSA > 0.05 ng/mL in the RP-alone group. Postoperative RT was well tolerated and did not add to the incidence of surgical complications. CONCLUSION: We propose that postoperative RT, as described here, helped to reduce the incidence of local recurrence and improved DFS to equal that of a lower-risk group of patients treated with RP alone. A randomized comparison is needed to define the role of adjuvant RT in patients with pT3N0 disease.     

Squamous cell carcinoma of the buccal mucosa: an aggressive cancer requiring multimodality treatment

BACKGROUND: In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. METHODS: During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. RESULTS: The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1-2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. CONCLUSIONS: SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1-2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3-4 or N+ disease and should also be considered for patients with T1-2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines.     

Radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate cancer: preliminary results

OBJECTIVE: To report an interim clinical evaluation of combined external beam irradiation (EBRT) and interstitial or regional hyperthermia in the treatment of locally advanced prostate cancer. PATIENTS AND METHODS: From 1997 to 2001, 26 patients with T3-4/NX/0M0 prostate carcinoma were treated with a combination of conformal EBRT and hyperthermia. Fourteen patients received five weekly regional hyperthermia treatments within an optimization (phase II) study, using the coaxial transverse electrical magnetic system. Twelve patients received one interstitial hyperthermia treatment within a feasibility study (phase I), using the multi-electrode current source system. Irradiation was delivered using a conformal three-field technique, administering 70 Gy in 2-Gy fractions in 7 weeks. RESULTS: The mean initial prostate-specific antigen level was 26 ng/mL. Three patients had a T4 and 23 a T3 tumour; the tumours were classified as well (four), moderately (16) and poorly (six) differentiated. The mean follow-up was 36 months. In the combined treatments there was no toxicity of more than grade 2. In regional hyperthermia the mean index temperature (T90 and T50, i.e. exceeded by 90% and 50% of the measurements) was 40.2 degrees C and 40.8 degrees C, and for interstitial hyperthermia 39.4 degrees C and 41.8 degrees C, respectively. All patients survived; seven patients had a biochemical relapse (27%), three in the regional and four in the interstitial group. The actuarial probability of freedom from biochemical relapse was 70% at 36 months for all patients together, 79% for regional and 57% for interstitial. No factors were found that could be used to predict relapse. CONCLUSIONS: The clinical outcome in these patients with advanced localized prostate cancer seems to compare favourably with most series using irradiation alone, and the treatment caused no severe complications.     

Obesity as a predictor of biochemical recurrence and survival after radiation therapy for prostate cancer

OBJECTIVE: Obesity has been demonstrated to predict biochemical progression in men undergoing radical prostatectomy for prostate adenocarcinoma, and is associated with a higher risk of biochemical and clinical relapse after radiation therapy (RT). We evaluated if obesity, determined by body mass index (BMI), is associated with adverse disease characteristics, pre-treatment serum testosterone, biochemical disease free survival (bDFS), disease-specific survival (DSS), or overall survival (OS) in patients undergoing radical external beam radiation therapy for prostate cancer. PATIENTS AND METHODS: A cohort of 706 patients with localized prostate adenocarcinoma treated with RT between 1993 and 2001 were categorized as obese (BMI > or = 30 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) or normal (BMI < 25 kg/m(2)). The association between BMI, disease characteristics, and progression were evaluated by Chi-square and ANOVA tests, Kaplan-Meier survival analysis, and Cox regression analysis. RESULTS: 195 patients (27.6%) were normal weight, 358 (50.7%) were overweight and 153 (21.7%) were obese. Obese men had lower serum testosterone levels than overweight and normal-weight men (means 12.8, 14.1, and 15.7 nmol/L, respectively; p < 0.001). The BMI groups did not differ in Gleason score, pretreatment PSA, or stage. On multivariate analysis, BMI group was predictive of reduced bDFS (p = 0.02) and DSS (p = 0.008), with a trend toward reduced OS (p = 0.062). CONCLUSION: Obesity was associated with lower serum testosterone levels but not with adverse pretreatment pathological features. Obese men have a higher risk of biochemical recurrence and prostate-cancer specific death after RT.     

RADICAL PROSTATECTOMY FOR PROSTATE CANCER: THE PERINEAL APPROACH INCREASES THE RISK OF SURGICALLY INDUCED POSITIVE MARGINS AND CAPSULAR INCISIONS

Purpose

We compare the incidence of positive surgical margins in patients who underwent perineal or retropubic radical prostatectomy for clinically localized (stage T1, T2) prostate cancer.

Materials and Methods

In this retrospective, nonrandomized study we reexamined the specimens of 94 consecutive patients who underwent radical perineal (48) or retropubic (46) prostatectomy for clinically localized prostate cancer (stage T1, T2) and with pathological stage pT2 (intracapsular), pT3A (established extracapsular extension without positive margins) or pT3B (extracapsular extension with positive margins) without lymph node involvement (N0). We assessed the presence or absence of extracapsular cancer with or without positive margins, incisions of the prostatic capsule exposing cancer (surgically induced positive margins) or benign glandular tissue. Patients were followed for 3 to 66 months (mean 25) using an ultrasensitive prostate specific antigen assay with a lower detection limit of less than 0.05 ng./ml.

Results

The overall incidence of positive margins in cancer tissue was 56% in the perineal and 61% in the retropubic group, and biochemical failure-free survival was 67% each. However, surgically induced positive margins in patients with organ confined disease were more frequent in the perineal than retropubic group (43 versus 29%, p <0.05) and associated with a 37% risk of biochemical failure (prostate specific antigen greater than 0.1 ng./ml.) at mean followup. In addition, capsular incisions exposing benign tissue were more frequent in the perineal than retropubic group (90 versus 37%, p <0.05) irrespective of pathological stage.

Conclusions

Although overall positive margins and biochemical failure rates are similar or identical for the perineal and retropubic approaches for organ confined prostate cancer, the perineal approach is associated with a significantly higher risk of capsular incisions and surgically induced positive margins and, thus, a higher risk of biochemical failure.     

Intermediate term biochemical progression rates after radical prostatectomy and radiotherapy in patients with screen detected prostate cancer

PURPOSE: We compared biochemical progression rates measured by increasing prostate specific antigen (PSA) levels using a standard definition of biochemical recurrence among patients with screen detected prostate cancer treated with radical prostatectomy (RP) or radiotherapy (RT). MATERIALS AND METHODS: A total of 1,939 patients diagnosed with clinically localized prostate cancer in a community based screening study from 1989 to 1998, followed through 2001, were treated with RP or RT and agreed to enroll in a followup study. This prospective cohort study (median followup 62 months, range 0.2 to 141) used adjusted Cox proportional hazards models to examine time to progression. Selection bias was addressed with propensity scores. Biochemical evidence of cancer progression was defined as PSA greater than 0.2 ng/ml in patients who underwent RP and 3 consecutive PSA increases as recommended by the American Society for Therapeutic Radiology and Oncology criteria for radiotherapy. RESULTS: Of the patients 17% had evidence of cancer progression. The percentage with progression-free survival at 5 and 9 years for RP was 84% and 76%, respectively, and for RT 80% and 70%, respectively. Cox proportional hazards models produced a hazard ratio of 1.63 (95% CI, 1.12, 2.38) for RT compared with RP, adjusting for clinical stage, Gleason grade, preoperative PSA, biopsy age, treatment year and propensity for treatment type. CONCLUSIONS: With intermediate term followup, patients treated with RT were more likely to have cancer progression than with RP adjusting for demographics, clinical factors, selection bias and treatment year.     

Characterization of biochemical recurrence after radical prostatectomy

BACKGROUND: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). METHODS: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. RESULTS: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. CONCLUSIONS: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.     

Hazard rates of disease progression after external beam radiotherapy for clinically localized carcinoma of the prostate

PURPOSE: We established hazard rates for disease progression at different intervals after external beam radiotherapy alone in patients with clinically localized prostate cancer. We determined the likelihood of biochemical failure in those free of disease 5 years after radiotherapy and identified those at risk for early versus late biochemical failure. MATERIALS AND METHODS: We reviewed the records of 964 patients treated with full dose external beam radiotherapy alone for T1 to T4, NxM0 prostate cancer. Followup prostate specific antigen (PSA) was measured 3 months after the completion of radiotherapy and every 3 to 6 months thereafter. Yearly hazard rates for biochemical failure were calculated each followup year. RESULTS: Median followup of the whole study group was 48 months. Overall 5 and 10-year biochemical disease-free survival rates were 63.7% and 53.6%, respectively. Patients had a peak overall hazard rate 2 years after treatment. The hazard rate then decreased until year 6, when it increased slightly and remained elevated even at year 10. This late increase in the overall hazard rate was associated with late increases in the hazard rate in men with favorable prognostic factors, namely pretreatment PSA less than 10 ng./ml., Gleason score less than 5, clinical T stage T1 or T2, posttreatment PSA nadir less than 0.99 ng./ml. or radiation dose less than 68 Gy. In 13 of the 307 patients (3.9%) with biochemical failure the failure occurred more than 5 years after initial treatment. CONCLUSIONS: The peak risk of biochemical failure is 2 years after radiotherapy. Patients are at slight but persistent risk for biochemical failure more than 5 years after treatment. Hazard rate calculations beyond the median followup of 4 years can underestimate the true hazard.     

The perioperative charge equivalence of interstitial brachytherapy and radical prostatectomy with 1-year followup

PURPOSE: We compare the comprehensive 1-year charges in a consecutive group of patients undergoing radical prostatectomy and transperineal interstitial brachytherapy for clinically localized prostate cancer at a single urban institution. MATERIALS AND METHODS: A total of 60 consecutive men with clinically localized prostate cancer (T1-T2, N0, M0) were treated during a 15-month period with radical prostatectomy or interstitial brachytherapy. Hospital and outpatient records were analyzed for each patient in regard to preoperative, operative and postoperative charges. Parameters included number of encounters, diagnostic and therapeutic interventions, hospitalization and operative charges, and followup visits, diagnostic tests and interventions for 1 year. All charge calculations were based arbitrarily on the 1996 Medicare fee schedule, factoring in the mandated global charge reimbursement period of 90 days for both procedures. RESULTS: Of the patients 38 underwent radical prostatectomy (prostatectomy group) and 22 underwent interstitial brachytherapy (brachytherapy group). The brachytherapy group was older with higher pretreatment serum prostate specific antigen and clinical stage disease, and more frequently received neoadjuvant hormonal therapy compared to the prostatectomy group. The 2 groups were similar in Gleason score and, when applicable, duration of neoadjuvant hormonal therapy. Preoperative charges were 15.3% lower for prostatectomy than for brachytherapy (not statistically significant). Conversely, operative charges for prostatectomy were 13.5% higher (p = 0.04). The major difference among preoperative, operative and postoperative charges was for those incurred postoperatively by the brachytherapy group, which were 56.0% higher than those for the prostatectomy group ($2,285.20 versus $1,007.20, p = 0.0004). CONCLUSIONS: Transperineal interstitial seed implantation is perceived by many as more cost-effective than radical prostatectomy for patients with clinically localized prostate cancer. We demonstrated that when such patients were followed for 1 year, the comprehensive charges for radical prostatectomy and interstitial brachytherapy were equivalent.     

Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer

PURPOSE: We evaluated patients at our institution who underwent radical prostatectomy for clinical stage T3 prostate cancer to determine their long-term clinical outcomes. MATERIALS AND METHODS: We reviewed our prospective surgical database and identified 176 men who underwent radical retropubic prostatectomy for clinical stage T3 prostate cancer from 1983 to 2003. Clinical and pathological data were reviewed and evaluated in a Cox proportional hazards model to determine preoperative predictors of biochemical recurrence. Clinical progression following biochemical recurrence was evaluated and clinical failure was defined as the development of clinical metastases or progression to hormone refractory prostate cancer. RESULTS: Of the 176 patients with cT3 prostate cancer 64 (36%) received neoadjuvant hormonal therapy. At a mean followup of 6.4 years 84 (48%) patients had disease recurrence with a median time to biochemical recurrence of 4.6 years. The actuarial 10-year probability of freedom from recurrence was 44%. On multivariate analysis biopsy Gleason score, pretreatment serum prostate specific antigen and year of surgery were independent predictors of biochemical recurrence. Neoadjuvant hormonal therapy was not a significant predictor of biochemical recurrence. Following biochemical recurrence clinical failure developed in 30 of 84 (36%) men with a median time of 11 years. Overall the 5, 10 and 15-year probabilities of death from prostate cancer were 6%, 15% and 24%, respectively. CONCLUSIONS: More than half (52%) of our patients remained free of disease recurrence following radical prostatectomy. In our series neoadjuvant hormonal therapy offered no advantage with respect to disease recurrence. Radical prostatectomy remains an integral component in the treatment of select patients with clinical stage T3 prostate cancer.     

Long-term Results of Definitive Treatment in Elderly Patients with Localized Prostate Cancer

Background: The indication and effectiveness of definitive local treatment for prostate cancer in patients with a limited life expectancy remains to be established. This study is a retrospective analysis of the long-term clinical outcome of elderly patients with localized prostate cancer treated by radiotherapy or a radical prostatectomy.
Methods: From 1982 to 1992, 37 patients with localized prostate cancer, aged 70 years or older, were treated initially by a pelvic lymphadenectomy and then with either external radiotherapy (n = 1 7) or a radical retropubic prostatectomy (n = 20). Lymph node metastasis was negative in all the cases, and no patients received hormonal treatment after the lymphadenectomy. The outcome of all patients was evaluated in June 1997.
Results: The 10-year overall and relative survival rates for the radiotherapy group were 27% and 85%, which were not significantly different from the rates of patients in the prostatectomy group (38% and 74%, respectively). The 5-year progression free rates for the radiotherapy group and the prostatectomy group were 63% and 95%, respectively ( P= 0.06).
Conclusion: In elderly patients with localized prostate cancer, the superiority of a radical prostatectomy over radiotherapy was not demonstrated in terms of either overall or relative survival rates, although the progression rate tended to be higher in patients in the radiotherapy group. The indication of definitive treatment in elderly patients should be further studied incorporating a quality of life assessment.     

High dose rate brachytherapy as a boost for the treatment of localized prostate cancer

PURPOSE: We report the outcome and toxicities of high dose rate brachytherapy as a boost for localized prostate cancer. MATERIALS AND METHODS: Between 1996 and 2003, 309 patients with prostate carcinoma were treated with external beam radiation therapy and high dose rate brachytherapy. Furthermore, 36% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 3 groups. Group 1 of 67 patients had Gleason score 6 or less, pretreatment prostate specific antigen 10 ng/ml or less and clinical stage T2a or less. Group 2 of 109 patients had Gleason score 7 or greater, pretreatment prostate specific antigen greater than 10 ng/ml and clinical stage T2b or greater. Group 3 of 133 patients had 2 or more of these higher risk factors. RESULTS: At a median followup of 59 months the 5-year biochemical control rate, as defined by the American Society for Therapeutic Radiation and Oncology, was 86%, cause specific survival was 98% and overall survival was 91%. Biochemical control in stratified groups 1 to 3 was 98%, 90% and 78%, respectively. On univariate analysis risk group, pretreatment prostate specific antigen and Gleason score were significant predictors of biochemical control. However, on multivariate analysis only risk group and pretreatment prostate specific antigen were significant. Using the Common Toxicity Criteria scale there were 2 cases of grade 3 acute urinary toxicity. Regarding late side effects 4% of patients had grade 3 genitourinary toxicity and 1 had a grade 4 rectal complication. CONCLUSIONS: External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent biochemical control, cause specific survival and overall survival with minimal severe acute or late complications.     

Salvage radiotherapy following radical prostatectomy

Biochemical relapse will occur in 17–64% of men who undergo radical prostatectomy, and up to a third of men with biochemical relapse will progress to develop metastatic disease and ultimately die of prostate cancer. Postoperative salvage radiotherapy (RT) to the prostatic fossa is well-tolerated and potentially curative treatment and should be considered for all men who have biochemical relapse following prostatectomy. Gleason score <8, prostate-specific antigen (PSA) doubling time >10 months and PSA re-emergence >2 years following surgery predict for a low risk of early metastatic failure, but even men with no favourable prognostic factors may have a long-term durable response to RT and should not be excluded from consideration of treatment on the basis of these factors alone. Positive surgical margin status and a positive anastomotic biopsy do not predict response to RT, and routine biopsy is not recommended. PSA level at time of RT is a strong indicator of durable response to RT. No one PSA cutpoint level appears to be more significant, and early RT is likely more effective than late. Contemporary PSA assays can detect biochemical relapse in the 0.01–0.2 range, and this may provide additional therapeutic advantage if treatment can be given when tumour burden is smallest. There is an urgent need for prospective data from randomised trials to optimally select patients for salvage RT, to determine the optimal time to initiate treatment and to determine the role of adjuvant hormone therapy, and all patients should be considered for entry into ongoing and future clinical trials.     

Treatment of localized prostate cancer using high-intensity focused ultrasound

OBJECTIVE: To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. PATIENTS AND METHODS: In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively. RESULTS: The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of <10, 10.01-20 and >20 ng/mL were 82%, 62% and 20% (P < 0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of <0.2, 0.21-1 and >1 ng/mL were 100%, 74% and 21% (P < 0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P < 0.001) was a significant independent predictor of relapse. CONCLUSION: HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.     

The ‘CaP Calculator’: an online decision support tool for clinically localized prostate cancer

Study Type – Prognosis (risk model)
Level of Evidence 2a

OBJECTIVE

To design a decision‐support tool to facilitate evidence‐based treatment decisions in clinically localized prostate cancer, as individualized risk assessment and shared decision‐making can decrease distress and decisional regret in patients with prostate cancer, but current individual models vary or only predict one outcome of interest.

METHODS

We searched Medline for previous reports and identified peer‐reviewed articles providing pretreatment predictive models that estimated pathological stage and treatment outcomes in men with biopsy‐confirmed, clinical T1‐3 prostate cancer. Each model was entered into a spreadsheet to provide calculated estimates of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node involvement (LNI). Estimates of the prostate‐specific antigen (PSA) outcome after radical prostatectomy (RP) or radiotherapy (RT), and clinical outcomes after RT, were also entered. The data are available at http://www.capcalculator.org .

RESULTS

Entering a patient’s 2002 clinical T stage, Gleason score and pretreatment PSA level, and details from core biopsy findings, into the CaP Calculator provides estimates from predictive models of pathological extent of disease, four models for ECE, four for SVI and eight for LNI. The 5‐year estimates of PSA relapse‐free survival after RT and 10‐year estimates after RP were available. A printout can be generated with individualized results for clinicians to review with each patient.

CONCLUSIONS

The CaP Calculator is a free, online ‘clearing house’ of several predictive models for prostate cancer, available in an accessible, user‐friendly format. With further development and testing with patients, the CaP Calculator might be a useful decision‐support tool to help doctors promote evidence‐based shared decision‐making in prostate cancer.     

The association of phosphodiesterase-5 inhibitors with the biochemical recurrence-free and overall survival of patients with prostate cancer following radical prostatectomy

PurposeTo determine whether phosphodiesterase-5 inhibitor documentation is associated with biochemical relapse-free and overall survival of patients with prostate cancer treated with radical prostatectomy.Materials and methodsWe undertook a retrospective cohort analysis of 3,100 patients with prostate cancer treated with radical prostatectomy between 2003 and 2015. The patients were categorized as a phosphodiesterase- 5- inhibitor user or non-user. The biochemical relapse-free and overall survival at 5-years and 10-years were determined.ResultsOf the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34–0.56) and for overall survival was 0.65 (CI 0.45–0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence.ConclusionThis retrospective analysis revealed a significant association of postoperative phosphodiesterase-5 inhibitor documentation with biochemical recurrence-free- and overall survival in patients with localized prostate cancer treated with radical prostatectomy. Larger scale studies are warranted to investigate the clinical significance of this association.     

Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy?

Study Type – Therapy (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Seminal vesicle invasion in prostate cancer has a poor prognosis. Nowadays, there is no consensus about the best adjuvant treatment after radical prostatectomy when seminal vesicle invasion is observed in the specimen. To our knowledge, this is the first comparative study between different adjuvant treatments after radical prostatectomy when seminal vesicle invasion is observed in the specimen.

OBJECTIVE

? To evaluate the biochemical‐failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI).

PATIENTS AND METHODS

? Between 1994 and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. ? Exclusion criteria were: detectable postoperative prostate‐specific antigen, lymph node metastases and follow‐up <18 months. ? Therefore, the study group included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26 received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant ADT combined with RT and 82 were monitored. The endpoint for this analysis was biochemical no evidence of disease (bNED). ? Preoperative prostate‐specific antigen level, specimen Gleason score, age, clinical stage, surgical margin status and adjuvant treatment were evaluated in a multivariable analysis with respect to bNED survival.

RESULTS

? After a mean (range) follow‐up of 60.3 (18–185) months, 88 (44.2%) patients had a biochemical relapse. ? The estimated 5‐ and 7‐year bNED survival were 32.6% and 25.9% for the observation group, 44.4% and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8% and 62.1% for the adjuvant ADT combined with RT group. ? On multivariate analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent prognostic factor of biochemical relapse.

CONCLUSIONS

? RP appeared to be insufficient as a single treatment for patients with SVI. ? The findings of the present study suggest that adjuvant ADT combined with RT after RP for patients with SVI confers a substantial benefit on 5‐year bNED survival.