Adjuvant radiotherapy after radical prostatectomy: indications, results and side effects

BACKGROUND: Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate-specific antigen (PSA) level as a sign of local and/or systemic tumor progression. Apart from a large number of retrospective investigations, available results are present only from three randomized studies which have either been completely published or are only in abstract form. RESULTS: For pT3 prostate carcinomas the data from the three randomized studies agree, showing an around 20% reduced biochemical progression rate after 4-5 years. With these data the results of numerous retrospective studies have been confirmed. The majority of the authors use total doses of 60 Gy with single doses of 2 Gy. From one randomized study an increased local control rate is proposed as the basis for the extended freedom from biochemical progression. The rate of acute and late side effects after three-dimensional radiotherapy with 60 Gy is very small and the rate of severe side effects is below 2%. The data for pT2 prostate carcinomas with positive margins are worse. Here controversy exists, and further investigations are required. In principle, however, adjuvant radiotherapy seems reasonable also for pT2 carcinomas with positive margins (determined by bNED - no biochemical evidence of disease). CONCLUSIONS: The effectiveness of adjuvant radiotherapy for patients with pT3 tumors and positive margins with and without detectable PSA levels is discussed. A survival advantage has not been demonstrated to date. For patients with positive margins in organ-limited prostate carcinomas (pT2 R1) randomized studies are recommended. It is unclear whether adjuvant radiotherapy is superior to radiotherapy for PSA levels increasing from the undetectable range after radical prostatectomy. To answer this question randomized studies are needed.     

Vermeidung des Lokalrezidivs durch eine adjuvante Strahlentherapie nach radikaler Prostatektomie

Depending on the tumor stage, 15-60% of patients develop a rise in PSA from levels around zero following radical prostatectomy. It is unclear whether this involves a local, systemic, or a mixed form of local/systemic progression. In addition to a multitude of retrospective studies, the results of three randomized trials are available that have already been published in full or in abstract form.For pT3 prostate cancer with extraprostatic extension, data are available from three randomized trials that consistently evidence an absolute decrease in biochemical progression rate of 20% after 4-5 years. These findings confirm the results of numerous retrospective studies. The large majority of authors employ total radiation doses of 60 Gy with single doses of 2 Gy. One randomized trial has shown that an increased local control rate is the basis for prolonged biochemical progression-free survival. The rate of acute and late radiation sequelae after three-dimensionally planned prostatic fossa radiotherapy (RT) with 60 Gy is very low; the rate of more severe late sequelae is <2%. Data on the status of pT2 prostate cancer with positive surgical margins are worse. The current findings are controversial and require further investigations. Basically, however, adjuvant RT is also possible for pT2 cancers with positive surgical margins. The efficacy of adjuvant RT for patients with positive surgical margins of pT3 carcinomas, whether or not they achieve PSA levels around zero, has been substantiated. A prolongation of survival time has, however, not yet been established because the follow-up period is too short. Randomized trials are still needed for cases of organ-confined prostate cancer (pT2 R1). It is unclear whether adjuvant RT is superior to RT when PSA levels increase beyond zero after radical prostatectomy. Randomized trials addressing this issue are still lacking.     

Durable efficacy of early postoperative radiation therapy for high-risk pT3N0 prostate cancer: the importance of radiation dose

Objectives. To determine the durable efficacy of early postoperative radiation therapy (RT) in patients with pT3N0 prostate cancer who were at an increased risk of biochemical failure. We also evaluated the long-term benefit derived from using higher RT doses.Methods. Seventy-nine patients with pathologic Stage T3N0 prostate cancer and high-risk postoperative features underwent RT within 6 months after surgery. No patient received prior hormonal therapy. Fifty-nine patients had positive surgical margin, 29 had pathologic seminal vesicle invasion, and 27 had persistently elevated postoperative prostate-specific antigen (PSA) levels. Freedom from biochemical relapse (bNED) was defined as an undetectable (less than 0.2 ng/mL) PSA level. Median follow-up time was 39 months, and the median radiation dose was 64.8 Gy. All patients were followed for at least 2 years to be considered biochemically controlled.Results. Patients receiving adjuvant RT for an undetectable pre-RT PSA level had a 3-year bNED rate of 90%, compared with 44% for those receiving salvage RT for a detectable level (P < 0.0001). In the group of adjuvant patients, RT doses more than 61.2 Gy resulted in a 3-year bNED rate of 90% compared with 64% for those receiving a lower dose (P = 0.015). The salvage patients irradiated with a dose of 64.8 Gy or greater had a 3-year bNED rate of 52% compared with 18% for those irradiated with lower doses (P = 0.048). Severe late RT-related complications were infrequent and did not correlate with dose.Conclusions. In patients with high-risk pT3N0 prostate cancer, an RT dose response may exist. Although some studies suggest limited durable efficacy for early postoperative RT, our data suggest that RT doses of 64.8 Gy or more appear superior to prevent future biochemical failures. A prospective randomized study evaluating a postoperative RT dose response is warranted.     

Salvage radiotherapy for pT3 prostate cancer with PSA failure after radical prostatectomy

We assessed the effectiveness of salvage radiotherapy in 13 patients at pathologic stage T3 (pT3) with prostate specific antigen (PSA) failure after radical prostatectomy: 9 patients at pT3a and 4 patients at pT3b. Three-dimensional dynamic conformal radiotherapy was used for all patients in this study, and the median radiation dose was 57.7 Gy (range, 44-70 Gy) in daily amounts of 2 Gy. The median follow-up after salvage radiotherapy was 643 days (range, 193-1562 days). In 12 of the 13 patients, PSA levels decreased after salvage radiotherapy, but in 1 patient, the PSA level increased and hence the treatment was discontinued at 44 Gy. However, 10 patients exhibited a lasting PSA response. The 3-year biochemical progression-free rate was 74%, and no serious acute or late toxicity was observed during the follow-up. Salvage radiotherapy is likely to become one of the effective treatments for the patients at pT3 with PSA failure following radical prostatectomy.     

Percutaneous radiotherapy for low-risk prostate cancer: options for 2007

Technical developments of radiotherapy (RT) over the recent years yielded in better conformation to the target volume thus increasing the therapeutic ratio and decreasing side effects. This paper discusses these options for low-risk prostate cancer. There has been evidence from randomized trials, that for low-risk PCA doses >70 Gy are significant better in case of biochemical disease-free survival (bNED). Image-guided radiotherapy (IGRT) has been proven in several studies for reduced safety margins around the prostate target volume. Intensity-modulated radiotherapy (IMRT) allow treatment with higher doses and 5-year results are reported from several studies. Data from several randomized trials about adjuvant RT after radical prostatectomy (RP) have been reported. In two phase-III trials a significant advantage of 20% bNED was demonstrated for doses between 76 and 79 Gy compared with 70 Gy. Using IGRT, the safety margin around the prostate can be reduced for about 30–50%. Doses of >80 Gy can be given safely to the prostate with IMRT and <5% grade-III/IV late side effects. Adjuvant RT for positive margins after RP has been of proven advantage. Three phase-III trials achieved a significant better bNED of 20% for 5 years. The effect of doses >70 Gy have been proven for low-risk PCA. IGRT resulted in reduced safety margins and a decrease of acute and late side effects. The addition of IMRT allowed higher doses to the prostate. Adjuvant RT after RP for positive margins achieved a significant better bNED.     

Salvage radiotherapy in patients with persistently detectable PSA or PSA rising from an undetectable range after radical prostatectomy gives comparable results

Purpose

Salvage radiotherapy (SRT) is applied routinely in patients with a biochemical relapse after radical prostatectomy (RP). Although the detection threshold for relapse after RP has steadily been lowered, only about 30 % of the SRT patients achieve a durable response. We have previously shown the association between a PSA decrease below detectable levels after SRT and biochemical progression-free survival (BPFS). After recalculating our data according to a more recent definition of biochemical failure after SRT, we now show the significance of the post-RP PSA nadir.

Materials and methods

Among 159 prostate cancer patients without hormonal treatment after RP, SRT was given to 72 patients with persistently detectable PSA after RP and to 87 whose PSA increased out of an undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to the prostate bed.

Results

The overall median follow-up time was 41.7 months. The probability for BPFS after this period was 52.8 % in 72 patients with persistently detectable PSA after RP and 65.4 % in 87 patients who had a post-RP PSA nadir below detection limit. Univariate and multivariate analyses showed no significant difference in BPFS of both patient groups (p > 0.05).

Conclusion

Our findings suggest that SRT is a viable treatment option for patients with persistently detectable PSA, giving similar results as in patients whose PSA increases out of an undetectable range after RP.     

Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study

Purpose

To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT).

Methods

Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses.

Results

Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8–10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030).

Conclusions

In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.     

Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) level, pT and Gleason score as predictors of PSA recurrence after radical prostatectomy: a multi-institutional outcome study in Japan

OBJECTIVE: To evaluate the clinical outcome of radical prostatectomy (RP) in Japan, by retrospectively analysing the clinicopathological data in patients with clinical T1-T2 prostate cancer treated by RP, as there can be prostate-specific antigen (PSA) recurrence after RP in substantially many patients, and its character can differ according to ethnic group and/or country. PATIENTS AND METHODS: We reviewed 1192 patients who had a RP from 1993 to 2002 with no neoadjuvant/adjuvant therapy and whose PSA level after RP decreased at least once to undetectable levels (<0.2 ng/mL). PSA recurrence was defined as > or = 0.20 ng/mL. The patient data were collected from the Urological Oncology Study Group, a subgroup of Japan Clinical Oncology Group. RESULTS: The patients' median (range) age was 67 (47-83) years and their PSA level before RP was 8.7 (1.0-153) ng/mL. During the median follow-up of 45.6 months, 302 of the 1192 patients (25.3%) developed PSA recurrence. The median time to recurrence was 369 (61-2128) days after RP. A log-rank test showed that five significant clinicopathological factors were associated with PSA recurrence after RP: the percentage of prostate needle-biopsy cores with cancer, the biopsy Gleason score, PSA level before RP, pathological stage, and the Gleason score of the RP specimen (P < 0.001 for all). In multivariate analyses, the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were all independent significant predictors of PSA recurrence after RP in Japanese men. CONCLUSIONS: The frequency of PSA recurrence after RP was 25.3% in Japan and the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were independent significant factors for PSA recurrence.     

Impact of Early Salvage Radiation Therapy in Patients with Persistently Elevated or Rising Prostate-specific Antigen After Radical Prostatectomy

Background

Salvage radiation therapy (SRT) is a recommended treatment option for biochemical recurrence after radical prostatectomy (RP). However, its effectiveness may be limited to specific categories of patients.

Organbegrenztes Prostatakarzinom mit positivem Resektionsrand

For pT3 prostate cancer with positive resection margins, the importance of postoperative radiation therapy is confirmed by a high level of evidence. However, for the pT2,R1 situation prospective, randomized studies concerning this question are lacking. Despite better local tumor control in the pT2 stage the PSA recurrence rate lies between 25% and 40% and positive margins are an independent factor for recurrence. Retrospective studies suggest a positive effect of adjuvant or salvage radiation for the oncological outcome in the pT2,R1 situation. On the other hand the side effects profile, with a potentially negative influence of postoperative continence and various delayed toxicities, is not insignificant despite modern radiation techniques and in the era of ultrasensitive PSA analysis should be considered in the risk-benefit assessment. As long as the optimal initiation of postoperative radiation therapy is unclear, the assessment of indications for adjuvant or salvage radiation for organ-limited prostate cancer with positive resection margins should be made after an individual patient consultation and under consideration of the recurrence risk factors, such as the Gleason grade and the localization and extent of the resection margins.     

Adjuvant radiation therapy for recurrent PSA after radical prostatectomy in T1-T2 prostate cancer

To evaluate retrospectively the efficacy of adjuvant radiation therapy (ART) in patients with T1-T2 prostate cancer (CaP) in whom extracapsular cancer (pT3) was detected after radical prostatectomy (RP), together with biochemical failure characterized by a recurrent level of serum prostate-specific antigen (PSA)>0.1 ng/mL. Twenty-two patients with T1-T2 CaP treated by RP who subsequently were found to have pT3 CaP with (13) or without (9) positive surgical margins and/or seminal vesicle invasion, exhibited biochemical failure characterized by a recurrent level of serum PSA, 2-40 (mean: 25) months after RP and were treated with ART (65 Gy). Bone and CT scans were negative in every patient, 15 of whom were submitted to TRUS biopsy (Bx) of the anastomosis (resection site), which was positive in 8. Patients were followed up for between 6 and 60 (mean: 32.5) months. Transient side effects (urgency, proctitis, diarrhea) were experienced by 9 patients after ART. A decrease in serum PSA was observed in 19 patients; however, only 14 of these achieved an undetectable level (<0.1 ng/mL) on one or more occasions after completion of ART (in 12 cases this was after 3 months). Of the 14 patients, 8 achieved a persistently unmeasurable PSA level at a mean follow-up of 20.4 (range: 9-48) months. There was no difference between patients in whom an undetectable level of serum PSA was attained and those in whom it was not, with regard to specimen pathology, PSA doubling time, timing of ART, and the result of Bx. Patients who achieved an undetectable PSA had a lower mean PSA at the time of ART (1.1 vs 2.9 ng/mL, P<0.05) and a lower preoperative mean PSA. Although ART for biochemical failure after RP may lead to undetectable PSA levels in a significant proportion of patients for a significant period of time, a longer follow-up shows that such unmeasurable levels persist in only 36.4% of such patients.     

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.     

When should we expect no residual tumor (pT0) once we submit incidental T1a‐b prostate cancers to radical prostatectomy?

Objectives: To date, no tool exists to predict pT0 at radical prostatectomy (RP) in patients with T1a–T1b prostate cancer (PCa) after surgery for benign prostatic hyperplasia (SxBPH). We aimed to fill this gap by developing a user‐friendly flowchart to assist urologists when incidental PCa is diagnosed and a clinical decision is required. Methods: We analyzed 158 T1a–T1b prostate cancers patients who underwent RP between 1996 and 2009. A risk stratification tool was developed applying the tree modeling technique of classification and regression tree analysis (CART) and relying on all the available pre‐RP characteristics (age, prostate‐specific antigen [PSA] before SxBPH, PSA after SxBPH, cT1a–T1b stage, prostate volume and Gleason sum at SxBPH). Then, the accuracy of the proposed model using 200 bootstrap resamples for internal validation was calculated. Results: A total of 95 patients (60.1%) were stage T1a, and 63 (39.9%) were stage T1b. The median values of PSA before and after SxBPH were 4.2 and 1.1 ng/mL, respectively. A total of 22 patients (13.9%) showed no residual tumor (pT0) at RP. The CART analyses identified three groups at risk of having residual disease at RP: (i) PSA after SxBPH > 1.0 ng/mL (pT0 prevalence: 3.8%); (ii) PSA after SxBPH < 1.0 ng/mL and PSA before SxBPH > 2.0 ng/mL (pT0 prevalence: 14.8%); and (iii) PSA after SxBPH < 1.0 ng/mL and PSA before SxBPH < 2.0 ng/mL (pT0 prevalence: 42.3%). The accuracy of the proposed model was 77.1%. Clinical stage (T1a vs T1b) was not associated with pT0 (P = 0.4). Conclusions: Clinical stage (T1a vs T1b) assessment does not help in predicting pT0 cases. An accurate and clinically useful flowchart to predict pT0 at RP after incidental prostate cancer diagnosis is provided herein.     

External beam radiation therapy after radical prostatectomy: efficacy and impact on urinary continence

INTRODUCTION AND OBJECTIVES: The efficacy of adjuvant and salvage external beam radiation (AXRT+SXRT) for prostate cancer after radical prostatectomy (RP) has been debated because of the inability to rule out systemic occult metastasis, uncertainty that radiation eradicates residual local disease and the potential of exacerbating impotency and incontinence. To characterize the effectiveness and treatment morbidity a retrospective review was performed. METHODS: In all, 38 patients received AXRT and 91 received SXRT. The SXRT group was stratified by PSA level, age, race, pathologic stage, margin status, worst Gleason sum, radiation dose and pelvic field. Complications evaluated were impotence and incontinence. Median follow-up was 60.2 months. RESULTS: The 5-y disease-free survival (DFS) rate was 61.3% for AXRT and 36.3% for SXRT. Multivariate analysis of the SXRT cohort showed Gleason score, pathologic stage and pre-XRT PSA to be predictors of disease recurrence. After XRT 26% had worsened continence. CONCLUSIONS: Patients who recur after RP whose pathologic stage is pT2 or pT3c, Gleason score of 8 or higher or pre-XRT PSA is >2.0 ng/dl may have microscopic metastatic disease and a decreased chance of cure with SXRT alone. Continence was further impaired after XRT.     

The outcome of patients with pathological Gleason score >or=8 prostate cancer after radical prostatectomy

OBJECTIVE

To analyse the outcome of patients undergoing radical prostatectomy (RP) for Gleason 8–10 clinically localized prostate cancer, and to evaluate the prognostic value of well‐known predictors of progression.

PATIENTS AND METHODS

In all, 1480 patients had RP between 1988 and 2006, of whom 180 had pathological Gleason score ≥8 and negative lymph nodes. Biochemical progression‐free survival was determined using the Kaplan‐Meier method. The effect of preoperative prostate‐specific antigen (PSA) level, pathological stage and margin status was assessed with univariate and multivariate analyses.

RESULTS

Of the 180 patients, the Gleason score in the RP specimen was 8, 9 or 10 in 70%, 27% and 3%, respectively; 24% had stage pT2 disease, 30% stage pT3a, 25% stage pT3b and 20% stage pT4a. The 5‐ and 7‐year biochemical progression‐free survival was 73 and 65% for stage pT2, 40% and 27% for stage pT3a, and 30% for stage pT3b (log rank test, P < 0.001). In the univariate model, preoperative PSA level, pathological stage and surgical margins were predictors of survival. In the multivariate analysis, preoperative PSA level and extracapsular extension predicted biochemical progression‐free survival.

CONCLUSION

Gleason 8–10 tumours have a poor prognosis. Patients with a PSA level of <10 ng/mL and stage pT2 disease have the greatest likelihood of having a longer progression‐free survival after RP.     

The 100-day PSA: usefulness as surrogate end point for biochemical disease-free survival after definitive radiotherapy of prostate cancer

Overall and biochemical disease-free (bNED) survival data after definitive radiotherapy (RT) for prostate cancer (CaP) requires decades of patient follow-up. Surrogates involving dynamics of prostate-specific antigen (PSA) decline, PSA nadir and time thereto have been unrewarding. This study investigated the metric of the PSA value 100 days after RT (PSA(100)), analyzed with respect to 8-y bNED survival. A total of 214 patients with T1-3 CaP were treated with definitive RT (defined as dose >66 Gy) in our institution between 1/1/1988 and 12/31/2000. All were subject to continuous follow-up with routine PSA levels. Biochemical failure (77 patients) was defined by the ASTRO criteria (n=67) or by the date of first hormonal therapy for a rising PSA, which did not meet the ASTRO criteria (n=10). No patients were included if they received postoperative radiation, or if hormones were administered prior to bNED recurrence, if any. Patients were stratified by PSA(100) values 4.0 ng/ml, and 4.0 ng/ml had 20% 8-y bNED survival (P<0.001). Use of a PSA(100) cutoff of 2.5 ng/ml yielded no significant difference in 8-y bNED survival (P=0.229). Cox proportional analysis revealed that initial PSA (P=0.006), stage (P=0.001) and PSA(100)相似文献   

Predictive factors of radiation therapy for patients with prostate specific antigen recurrence after radical prostatectomy

OBJECTIVE: To assess the efficacy of salvage/adjuvant radiation therapy (RT) for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Between 1997 and 2001, 52 patients were treated in our institution with RT for PSA recurrence after RP. The mean (range) delay between RP and RT was 30.5 (0.16-105.6) months. Eighteen patients received no hormonal therapy before RT. The failure of RT was defined as three consecutive increases in PSA levels with intervals of > or = 6 weeks. RESULTS: Within a mean (range) follow-up of 27.7 (6-69) months, 18 patients presented with biochemical progression. The 3-year biochemical progression-free survival was 51%. Using univariate analysis, an age < 65 years (P = 0.0262), a Gleason score on the RP specimen of > or = 8 (P = 0.0024), stage pT3 (P = 0.02), a detectable nadir PSA after RT (P < 0.001) and the absence of hormonal therapy (P = 0.0359) were associated with a lower biochemical progression-free survival. However, only the Gleason score (P = 0.0395) and nadir serum PSA after RT (P = 0.028) remained independent predictive factors on multivariate analysis. CONCLUSION: Half of the present patients treated with RT for an isolated high serum PSA level after RP were free of biochemical relapse at 3 years of follow-up. RT may be proposed to selected patients with mild morbidity. However, definitive evidence of the beneficial effect of adjuvant RT for patients with PSA recurrence after RP awaits the conclusion of randomized clinical trials.     

Long-term benefits of elective radiotherapy after prostatectomy for patients with positive surgical margins

PURPOSE: The benefit of adjuvant radiotherapy after prostatectomy for patients with pathological risk factors but with an undetectable postoperative PSA remains controversial. In this retrospective study we define the benefits of elective postoperative radiotherapy in this setting. MATERIALS AND METHODS: A total of 44 patients received elective postoperative radiotherapy at a single institution in the PSA era (1989 to 1995) for positive surgical margins and undetectable postoperative PSA. Radiotherapy was delivered to a median dose of 60 Gy. Clinical target volume included the prostate bed. Pelvic nodes were not treated. The four-field box technique with customized blocking of bladder, rectum and small bowels was used and defined the planning target volume. The patients were then compared to a contemporaneous group of 189 patients with positive surgical margins who underwent radical prostatectomy without any adjuvant therapy. Failure was defined as biochemical (PSA) recurrence and was timed from first detectable PSA. RESULTS: The 5 and 10-year biochemical no evidence of disease was 90.9% and 90.9% for the elective postoperative radiotherapy group, and 66.4% and 54.5% for the observation group, respectively (p = 0.0012). Median time to biochemical failure was also longer in the elective postoperative radiotherapy group (88.6 months) compared to the observation group (43.5 months) (p <0.001). Risk factors for biochemical recurrence on multivariate analysis were Gleason score greater than 7 (p = 0.017), established extracapsular extension (p = 0.002) and lack of elective postoperative radiation (p = 0.001). CONCLUSIONS: This is one of the longest followup studies showing that elective postoperative radiation therapy is associated with improved bNED and prolonged time to recurrence. Combined radical prostatectomy and elective postoperative radiotherapy should be considered in the management of high risk prostate cancer, especially in the presence of positive surgical margins despite undetectable PSA.     

Salvage radiotherapy for biochemical recurrence after radical prostatectomy

OBJECTIVE: To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. PATIENTS AND METHODS: Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. RESULTS: The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. CONCLUSION: Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective.     

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.