 is professor of surgery in the division of urology at Albany Medical College in New York.

Badar M. Mian, MD

Three different randomized trials comparing adjuvant radiotherapy (RT) with salvage RT (sRT), all including men at high risk of recurrence post radical prostatectomy (post-RP), have demonstrated that adjuvant RT does not improve oncological outcomes.

 Consequently, early sRT (delivered after some increase in prostate-specific antigen [PSA] level) has emerged as the de facto standard approach to post-RP men with adverse pathology. The oncologic benefits of RT dose escalation for treating primary prostate cancer have been well established over the last 20 years. However, the optimal dose and timing of post-RP RT to treat any residual microscopic prostate cancer have remained controversial. To address these questions, 2 recent studies examined the outcomes of early vs delayed RT, and of RT dose escalation, on health-related quality of life (HRQOL) and functional outcomes.

Is higher-dose salvage RT superior to the standard dose?

 conducted a prospective, open-label, multicenter, randomized phase 3 trial with the aim to demonstrate the superiority of dose-escalated sRT over the standard-dose sRT (

 hormonal therapy) in terms of biochemical (PSA) progression. Men in the standard-dose sRT (control) group received 64 Gy and those in the dose-escalated group received 70 Gy, with 175 patients in each group. The median PSA at randomization was 0.3 ng/mL (75% with PSA ≤ 0.5 ng/mL). Median follow-up was 6.2 years.

The median PSA progression-free survival was similar in the standard and dose-escalated arms, at 8.2 years and 7.6 years, respectively (log-rank 

 = .4). Other outcome measures such as clinical progression, time to hormonal treatment, and overall survival also did not differ between the 2 arms. The estimated biochemical progression–free rate at 6 years was 62% in the control arm and 61% in the dose-escalated arm.

Late grade 2 and 3 genitourinary (GU) toxicity was observed in 21% and 7.9% of patients in the control arm and 26% and 4% patients in the dose-escalation arm, respectively, which were statistically similar between the groups. However, late-grade 2 gastrointestinal (GI) toxicity was observed at a higher rate in the dose-escalation group: 7.3% in the control arm vs 20% in the higher-dose arm (odds ratio, 2.20; 

 = .009). Grade 3 erectile dysfunction did not differ significantly between the 2 arms (27% vs 30%; 

: NS). For late GU toxicity, the grade 2 incidence was higher in those men who underwent 3D-conformal RT (35%) than in those who underwent intensity-modulated RT/rotational techniques (26%).

Does early salvage RT affect quality of life?

To assess the effect of timing of post-RP RT, Westhofen et al

 conducted a propensity score-matched retrospective analysis of a large contemporary patient cohort. Men were divided in 2 study group including those men receiving early RT (eRT; within 6 month after RP) vs those receiving deferred RT (dRT). The investigators evaluated the HRQOL using the validated European Organization for Research and Treatment of Cancer (EORTC) QOL C30 (EORTC QLQ-C30) questionnaire, as well as on functional outcomes following RT.

The primary end point was HRQOL, with good general HRQOL defined as global health status (GHS) of higher than 70 (out of 100). Patient-reported outcomes were obtained through mailed-in questionnaires to 1599 eligible patients at 6 weeks (postop), 12 months, 24 months, 36 months, and 48 months after surgery. The inclusion criteria for post-RP RT included stage pT3 or higher, high-risk International Society of Urological Pathology Grading System grade 4 or 5, or positive surgical margins.

Of the 1599 patients, 307 patients received eRT whereas 1292 patients were observed and treated with dRT. After propensity score matching, the two groups were similar in age, body mass index, preoperative PSA, tumor stage, Gleason score, lymph node involvement, nerve sparing status, and surgical approach.

In the eRT subgroup, all 307 patients received RT within 6 months, whereas in the dRT subgroup, 27.0% had received dRT by 12 months after RP, 44.4% at 24 months, 46.2% at 36 months, and 51.4% at 48 months. Median PSA prior to RT was 0.13 ng/mL in the eRT group and 0.18 ng/mL in the dRT group.

International Index of Erectile Function–5 scores were significantly better in the dRT group at 12 and 24 months, but were similar at 36 and 48 months among the eRT and dRT groups. Similarly, the mean International Consultation on Incontinence Questionnaire–short form scores were significantly better for the dRT group at 12 and 24 months. Continence recovery rates were higher in the dRT group than in the RT group at 12, 24, and 36 months.

HRQOL scores were generally higher in the dRT group at 12 and 24 months, with significantly higher mean GHS scores compared to the eRT group. Good general HRQOL was reported by 35.5% (eRT) vs 52.7% (dRT) after 12 months, and 37.3 % (eRT) vs 45.8% (dRT) after 24 months (

 > .02). Multivariate regression analysis identified dRT as an independent predictor of good general HRQOL. Further, the longer time interval from RP to RT was an independent predictor of increased postoperative general HRQOL in univariate analysis (OR, 1.09; 95% CI, 1.04-1.14; 

It is apparent from the results of these 2 studies that neither the higher-dose RT nor early RT after RP provide sufficient oncological benefits to justify the adverse impact on functional outcomes and HRQOL. Dose-intensified sRT was not superior to conventional-dose sRT, but it was associated with higher rates of late grade 2 GI toxicity. A limitation noted in the higher-dose sRT study is the relatively small proportion of patients with Gleason score ≥ 8 and/or pT3b disease.

To improve the outcomes for patients with biochemical progression after RP, selection criteria should be adjusted to identify patients (e.g. those with multiple high-risk features) who are more likely to benefit from more intensified RT dose or schedule. The anticipated wider availability of prostate-specific membrane antigen (PSMA) PET scans will improve risk stratification and patient selection for postoperative RT by rendering visible the disease foci that are currently invisible on conventional imaging. However, the impact of the inevitable stage-shift related to PSMA scans and any potential oncologic and functional benefits will remain unclear for years to come.

At present, however, an initial period of observation and deferred RT, appears to be a safe and effective approach for most post-RP patients with high-risk pathology in order to avoid the adverse effects on HRQOL, without compromising cancer control.

1. Vale CL, Fisher D, Kneebone A, et al; ARTISTIC Meta-analysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. 

2020;396(10620):1422-1431. doi: 10.1016/S0140-6736(20)31952-8

2. Ghadjar P, Hayoz S, Bernhard J, et al; Swiss Group for Clinical Cancer Research (SAKK). Dose-intensified versus conventional-dose salvage radiotherapy for biochemically recurrent prostate cancer after prostatectomy: the SAKK 09/10 randomized phase 3 trial. 

Published online June 14, 2021. doi: 10.1016/j.eururo.2021.05.033

3. Westhofen T, Buchner A, Schlenker B, et al. Timing of radiotherapy after radical prostatectomy: effects on health-related quality of life. 

Published online June 29, 2021. doi:10.1097/JU.0000000000001930

Articles

"It is apparent from the results of these 2 studies that neither the higher-dose RT nor early RT after RP provide sufficient oncological benefits to justify the adverse impact on functional outcomes and HRQOL," writes Badar M. Mian, MD.

Postprostatectomy radiation dose and timing affect quality of life

Despite maintaining castrate levels of testosterone through the use of androgen deprivation therapy and antiandrogens, some men with metastatic prostate cancer will develop castration-resistant prostate cancer (CRPC). Metastatic CRPC (mCRPC) remains an incurable disease state with relatively short survival. Recent advances in the treatment of mCRPC have included cell cycle checkpoint inhibitors and drugs targeting cancers with genomic alterations (

A targeted therapeutic approach to mCRPC was studied in a phase 3 clinical trial (VISION, NCT03511664) to determine the efficacy and safety of delivering lutetium-177 (

Lu) to prostate-specific membrane antigen (PSMA)-expressing mCRPC cells. The trial was presented at the 2021 ASCO annual meeting and results were also published in the 

Lu-PSMA-617 delivers beta-particle radiation preferentially to PSMA-positive cells and the surrounding microenvironment. PSMA expression increases with increasing stages of prostate cancer and is associated with poor prognostic indicators. mCRPC lesions in most patients are PSMA-positive, and increased expression has been independently associated with reduced survival.

The VISION trial included patients who had experienced disease progression to mCRPC after receiving 1 or more approved androgen-receptor–pathway inhibitors and with 1 or more taxane-based chemotherapy regimens. PSMA positivity on the basis of gallium-68 (68Ga)-labeled PSMA-11 (68Ga-PSMA-11) PET-CT imaging at baseline was required for confirmation of radionuclide binding. To qualify as PSMA-positive mCRPC, at least 1 PSMA-positive metastatic lesion was required, without any PSMA-negative lesions.

The trial was conducted at 84 sites (52 in North America and 32 in Europe) between June 4, 2018, and October 23, 2019. Of the 1003 patients who underwent scanning, 831 (82.9%) met the eligibility criteria for PSMA positivity on PET scan. They were randomly assigned to receive either 

Lu-PSMA-617 plus standard of care (551 men) or standard of care alone (280 men). Patients were randomized in a 2:1 ratio to receive either 

Lu-PSMA-617 plus standard of care (study group) or standard of care (control group) alone. Standard of care included androgen suppressive therapies to maintain castration level testosterone, but without any concurrent cytotoxic chemotherapy, systemic radioisotopes, immunotherapy, etc. The study group received intravenous infusions of 

Lu-PSMA-617 (dose of 7.4 GBq (200 mCi)) once every 6 weeks for 4 cycles. In patients with evidence of response, 2 additional cycles (up to 6 cycles in total) were allowed at the discretion of the treating physician.

Follow-up imaging with CT scan or MRI and bone scans were scheduled every 8 weeks for 24 weeks and then every 12 weeks. The median follow-up was 20.3 months in the study group and 19.8 months in the control group. The trial was designed to evaluate 2 co-primary end points, imaging-based progression-free survival (PFS), and overall survival (OS). Secondary end points included objective response and disease control, safety profile of 

Lu-PSMA-617 and health-related quality-of-life, pain, and biomarker outcomes.

Among all 831 patients who had undergone randomization, improved median OS was noted in the 

Lu-PSMA-617 treatment group when compared with the control group, 15.3 months vs 11.3 months, respectively (hazard ratio [HR] for death, 0.62; 

 < .001). In the group of 581 patients in the analysis set, the median imaging-based PFS was 8.7 months in the treatment group, as compared with 3.4 months in the control group (HR for progression or death, 0.40; 

For the 581 patients in the analysis set, the median time to the first symptomatic skeletal event or death was 11.5 months in the treatment group and 6.8 months in the control group (HR, 0.50; 

 < .001). Among the 248 patients who had measurable target lesions on PSMA PET scan, a complete response was noted in 9.2% men in the treatment group and none in the control group. A partial response was noted in 41.8% in treatment group and 3% in the control group. Similarly, confirmed decreases in the prostate-specific antigen level of at least 50% and 80% from baseline were noted at a higher level in the treatment group, and the time to worsening of quality of life and pain scores favored the treatment group.

Targeted therapies, including radioligand therapies such as 

Lu–PSMA-617, have the promise to affect only the cancer cells while sparing normal tissues, especially when selecting candidates using molecular imaging to confirm radionuclide binding. However, adverse events (AEs) still occurred in a higher proportion of men treated with the targeted therapy, compared with the controls. Grade 3 or higher AEs were noted in 52.7% of men in the treatment group and 38.0% in the control group. Fatigue, dry mouth, and nausea were the most common AEs in the treatment group. Significantly higher rate of anemia, thrombocytopenia, and lymphopenia were noted in the treatment group, and 12% required discontinuation of treatment with 

Although the OS increase by a median of 4.0 months may appear a modest improvement, it should be noted these patients were heavily pretreated using androgen deprivation as well as antiandrogen and taxane chemotherapy. The use of 

Lu-PSMA-617 significantly extended both the imaging-based survival and overall survival. Further, the time to symptomatic skeletal events, worsening of health-related quality of life and pain were all delayed following treatment with this radioligand targeted therapy. These benefits, along with low incidence of severe AEs, suggest that the addition of 

Lu-PSMA-617 to standard of care for mCRPC appears to be well tolerated, safe, and effective.

1. Sartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. 

Published online June 23, 2021. doi:10.1056/NEJMoa2107322

"The use of 177Lu-PSMA-617 significantly extended both the imaging-based survival and overall survival," writes Badar M. Mian, MD.

Improved survival is found in mCRPC after PSMA-targeted therapy 

Although much of our attention in treating patients with bladder cancer (BC) is focused on cancer control, patients and their families must face other real-life issues that significantly impact survivorship. Despite being of critical importance to the patients, health-related quality of life (HRQOL) after various treatments for BC has remained underappreciated until recent years. Previous studies on HRQOL have been small and limited in scope, focusing mainly on radical cystectomy (RC) or radiation therapy (RT) for muscle-invasive bladder cancer (MIBC) and the related urinary, bowel, and sexual dysfunction. The HRQOL after non–muscle-invasive bladder cancer (NMIBC) and how BC-related QOL compares with other pelvic cancers are not well understood.

To address this gap in knowledge, Catto et al conducted a population-level study of HRQOL of patients between 1 and 10 years since BC diagnosis.

 The authors used a mail-in survey between January 2007 and December 2016 of patients diagnosed in 22 British National Health Service hospitals (representing 11% of the population). Patients with BC were identified through the National Cancer Registration and Analysis Service and were asked to participate in the survey. Several tools were used such as general HRQOL questionnaire including questions related to mobility, self-care, daily activities, pain/discomfort, and anxiety/depression. The European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (which includes functional and symptom scales, financial impact, global QOL scale) was combined with EORTC-NMIBC QOL questionnaire to assess urologic symptoms.

Of the 3279 eligible participants, 1796 (55%) completed the survey. The average age of respondents was 75 years (11% were younger than 65 years), and only 1.0% were non-White. The nonresponders were older and lived in underserved areas. At least 1 long-term comorbid condition was reported by 76%, and 11% reported 4 or more comorbidities (hypertension, 24%; coronary artery disease, 14%; and diabetes, 11%). Of the respondents, 48% (n = 868) had treatment for NMIBC (transurethral resection of bladder tumor [TURBT]±intravesical treatment), 23% underwent RC alone, 17% received RC plus neoadjuvant chemotherapy (or prior BCG), and 7% underwent RT with curative intent.

Of the respondents, 69% reported at least 1 problem on the general HRQOL, with the most frequently reported issues including difficulty with mobility, daily activities, and pain/discomfort. The overall mean self-assessed health (SAH) score was 74 (out of 100), and it did not differ based on cancer stage (MIBC or NMIBC) or extent of treatment, eg, SAH score ranged from 75 in the RC-alone group to 71 in the RT group.

Regardless of treatment type, increasing age and number of comorbidities were associated with increasing frequency of reported problems in all general HRQOL domains (mobility, self-care, daily activities, and pain) with the exception of anxiety/depression, which was highest in the younger age groups. Also, multimodal treatment combinations (TURBT with/without intravesical treatment, RC with/without chemotherapy) did not impact HRQOL.

On the cancer-related QOL questionnaire, the mean global health score was 71 (out of 100) after RC compared with 69 after radical RT. No meaningful differences in scales or symptom scores were noted among the treatment groups (TURBT, RC, or RT) or cancer stages (I to IV). However, worse functional and symptom scores were noted with increasing age and comorbid conditions. Of note, a higher rate of financial difficulties was reported by younger patients—and especially in the younger patients undergoing RC—compared with those undergoing TURBT.

On the BC-specific QOL measures, bladder symptom scores varied considerably across different treatments and tumor stages. Worse urinary symptoms were reported following RT compared with TURBT, whereas urinary symptoms in participants following RC with neobladder were similar to those following TURBT. Also, addition of intravesical therapy to TURBT did not worsen the urinary symptoms. Worse problems with body image, sexual intimacy, sexual enjoyment, and male sexual problems were reported by those who underwent RC, which worsened with increasing age. The missing responses regarding sexual problems in women did not allow for an accurate evaluation of this domain.

Because only 12% of patients underwent ileal neobladder, the comparisons of HRQOL between various urinary diversions were not informative due to mismatch in sample size, age, and health of patients. Interestingly, there were no significant differences in HRQOL scores in each questionnaire based on the time from diagnosis of BC, possibly suggesting that HRQOL may stabilize after some time.

The general HRQOL was worse after treatment for BC than for prostate or colorectal cancer treatment across all domains except anxiety/depression. The differences were greatest for problems with mobility and daily activities. For example, 48% of men with bladder cancer reported problems with mobility compared with 36% of men with colorectal cancer, 34% of men with prostate cancer, and 25% of the general male population.

Higher rates of sexual dysfunction were reported by men with bladder cancer, and significant financial toxicity was reported in younger patients. Compared with the general population and those with other common pelvic cancers, patients with BC reported lower HRQOL. The use of multimodality treatment did not appear to adversely affect the HRQOL. Participants who received TURBT alone or TURBT with intravesical therapies and those who underwent RC alone or RC with systemic chemotherapy had similar urinary symptoms and sexual function scores. “It was reassuring that overall QOL in our participants was mostly associated with their age and fitness, rather than treatment intensity or treatment received. This should reassure patients and encourage them to make the safest choice - with respect to their cancer”, remarked lead author James Catto, MBChB, PhD, professor of urological surgery at theProfessor James Catto from the University of Sheffield in the United Kingdom.

Financial toxicity reported by younger patients receiving RC or TURBT was significantly higher than that reported by older patients; this is likely related to disruption in employment due to frequent visits required for cystoscopy and/or intravesical therapy or the temporary inability to work for 2 to 3 months or longer after radical surgery. Catto pointed out, “The most frequent problems in younger men < 65 years was loss of sexual function,” and that “financial toxicity for both NMIBC and MIBC was common in younger, still employed men, both of which require consideration when planning treatment.” Knowing the expected deterioration in sexual function and financial health associated with BC treatment should prompt early and specific counseling and mitigative strategies. Although more intense treatment schedules may not have affected many of the HRQOL measures, deintensification of treatment may be necessary to reduce financial toxicity.

As the investigators pointed out, the survey was conducted among participants in a public (free) health care system, and because the nonresponders were typically older and from underserved areas (both of which contribute to poor HRQOL), the full extent of BC-related decline in HRQOL of the population is likely to be worse than reported in the study.

The variation in overall HRQOL depending upon patient age and comorbidities may not be surprising, but the lack of difference in HRQOL based on treatment type, disease stage, or time from diagnosis may be unexpected. Trimodal therapy for BC is being discussed with increasing frequency to avoid radical surgery. The patient-reported HRQOL noted in this study showed no significant differences in outcomes between RC and RT; however, the cohort undergoing RT was small and older. Could an individual with high-grade NMIBC be offered either TURBT plus intravesical BCG or radical cystectomy with sufficient equipoise? This study provides important and clinically useful information that can be used to plan the intensity of treatment and counsel our patients regarding the cancer-related and QOL-related outcomes after treatment.

Catto JWF, Downing A, Mason S, et al. Quality of life after bladder cancer: a cross-sectional survey of patient-reported outcomes. Eur Urol. 2021;79(5):621-632. doi:10.1016/j.eururo.2021.01.032

"This study provides important and clinically useful information that can be used to plan the intensity of treatment and counsel our patients regarding the cancer-related and QOL-related outcomes after treatment," writes Badar M. Mian, MD.

QOL after bladder cancer treatment vs other cancers

Due to the low sensitivity of imaging studies, pelvic lymph node dissection (PLND) remains the most effective method for staging of prostate cancer. Due to paucity of randomized controlled trials (RCT), the role of various PLND templates, in terms of prognostic and therapeutic benefits, has remained controversial. Some experts believe that standard or limited PLND (LPLND) is sufficient for staging whereas others strongly support the use extended PLND (EPLND) for its potential to remove more lymph nodes and micrometastases. Two recently reported RCTs within the past 6 months are now available to illuminate this subject. The RCT by Lestingi et al

 report the results of an RCT that was designed to address the questions regarding the therapeutic benefits (ie, biochemical recurrence [BCR]-free survival) of EPLND compared to LPLND. From October 2011 to March 2017, of 1477 men undergoing radical prostatectomy and bilateral PLND, 700 men were randomized to the LPLND template and 740 to the EPLND template group. Instead of individual patient randomization, a cluster randomization strategy was employed for ease of consent and logistics of trial execution. The surgeons were cluster-randomized every 3 months to perform either LPLND or EPLND. Two surgeons were removed from the study in June 2015 for poor compliance with the randomized assignments.

Of the randomized patients, no PLND was performed in 42 and 55 patients in the LPLND and EPLND groups. Thirty-seven patients were excluded either due to withdrawal of consent (8) or being lost to follow-up (29). The distribution of biopsy Gleason scores (GS) in the LPLND and EPLND groups was 18% and 22% for GS of 8 or higher, 19% and 17% for GS 4+3, 52% and 52% for GS 3+4, and 10% and 9.4% for GS 6, respectively.

In terms of lymph node yield, a median of 12 lymph nodes were removed in the LPLND group compared with 14 in the EPLND group. The rate of lymph node metastasis (pN1) was 12% in the LPLND arm and 14% in the EPLND arm (

After a median follow-up of 3.1 years, 388 (26.9%) BCR events occurred in the entire cohort. Regardless of how the data were analyzed, there was no difference in the BCR rates between the LPLND or EPLND (

=.5) groups. Overall, the rates of Clavien-Dindo grade 2 and grade 3 complications (including deep vein thrombosis or lymphocele) were similar in the LPLND and EPLND groups at 7.3% and 6.4%, respectively. There were no grade 4 or 5 complications.

Similar lack of therapeutic effect of EPLND was noted in another RCT reported by Lestingi et al a few months ago. Although these 2 trials cannot be compared directly, there are several baseline differences amongst the trials worthy of consideration. The current trial was sufficiently powered with 1477 patients, compared with 300 patients in the earlier study. One main difference among the trials was in the EPLND template. The earlier trial by Lestingi et al included the common iliac nodes in the EPLND template, which yielded median 17 lymph nodes, but not in the current trial, which yielded median 14 lymph nodes. Conversely, the median lymph node count with LPLND in the current trial was much higher than in the earlier trial (12 vs lymph nodes 3 lymph nodes, respectively), and the rate of pN1 in the LPLND group was 12% in the current trial and only 3.4% in the earlier trial. Other nonrandomized series of PLND have demonstrated different results than the current trial, showing an increased number of lymph nodes with EPLND, and increase in the rate of pN1, according to John W. Davis, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Although studies have reported variability in the correlation between more lymph nodes removed and higher rate of pN1, none have demonstrated a difference in BCR rates between LPLND and EPLND groups. Further, the benefit of 

 PLND in patients with intermediate-risk prostate cancer, which comprises the majority cohort in both of the RCTs, is subject to debate. A recent report by Altok et al evaluated the impact of omitting the PLND in cases with biopsy GS of 3+4 or lower, T1-2 who are subsequently upgraded to prostatectomy GS 4+3 or lower, or stage pT3.

 They noted that omission of PLND in appropriately matched cases did not alter the rate of BCR compared with those who underwent PLND (regardless of template). The current trial did not report the outcome of 97 patients in whom a PLND was omitted.

The authors of this RCT reported that the complication rates were similar in the LPLND and EPLND groups, which is similar to what has been reported by other nonrandomized studies, and is reflective of this author’s experience. Yet a recent large, systematic review and meta-analysis of this subject suggests otherwise. A study by Cacciamani et al reviewed 176 studies (77,303 patients) undergoing PLND.

 Intraoperative complications were noted in 1.8% and postoperative complications in 14.1%. The limited or standard PLND group experienced fewer complications (risk ratio, 0.55; 

=.01), especially lymphoceles and thromboembolic events, when compared with EPLND. EPLND was an independent predictor of increased complications, especially lymphocele formation (risk ratio, 1.77; 

When comparing this trial with other studies, the median lymph node count in the LPLND cohort were higher, and in the EPLND cohort was lower than expected. The lymphatic and fibrofatty tissue removed during PLND are contiguous and not anatomically compartmentalized based on the arbitrary template boundaries assigned by surgeons. The surgical technique and tissue handling by various surgeons can easily result in variations in lymph node count within the same template.

The lack of difference in the lymph node yield between the LPLND and EPLND templated noted in this RCT raises interesting questions about surgical technique, trial design, compliance with instructions, and surgical bias. This is illustrated by the fact that surgeons retrieved more lymph nodes from patients with high-risk prostate cancer even when they were assigned to perform LPLND. Knowledge of tumor characteristics and the awareness that their work is being reviewed may have influenced the surgical technique, resulting in higher-than-expected lymph node counts in the LPLND group and thus obscuring any potential differences in node count, pN1, or BCR rates.

It is common practice in uro-oncology to perform EPLND for high-risk prostate cancer. It remains unclear whether the increased lymph node yield or increased pN1 rates have any therapeutic effect on BCR. Neither the current nor the previous RCTs (and several nonrandomized studies) have reported any improvement in BCR rates with the use of EPLND. However, the median follow-up in both RCTs was relatively short and most patients harbored low- or intermediate-risk disease, which makes it difficult to draw firm conclusions.

Three decades into prostate-specific antigen screening–detected prostate cancer, the prognostic and therapeutic impacts of various types of pelvic lymph node dissection remain unclear. The role of PLND will be further challenged when more sensitive imaging and staging modalities (such as prostate-specific membrane antigen PET scan) become readily available. Although it’s likely that the urologists will continue to utilize EPLND despite unclear prognostic value, this will have to be balanced with the lack of therapeutic advantage, additional surgical time and cost, and possible increase in complications associated with EPLND.

1. Lestingi JFP, Guglielmetti GB, Trinh Q-D, et al. Extended versus limited pelvic lymph node dissection during radical prostatectomy for intermediate- and high-risk prostate cancer: early oncological outcomes from a randomized phase 3 trial. 

2021;79(5):595-604. doi:10.1016/j.eururo.2020.11.040

2. Mian BM. Extended pelvic lymph node dissection during RP does not appear beneficial. 

January 8, 2021. Accessed April 26, 2021. 

3. Touijer KA, Sjoberg DD, Benfante N, et al. Limited versus extended pelvic lymph node dissection for prostate cancer: a randomized clinical trial. 

Published online April 14, 2021. doi:10.1016/j.euo.2021.03.006

3. Altok M, Chapin BF, Matin SF, Achim MF, Gregg JR, Davis JW. Therapeutic consequences of omitting a pelvic lymph node dissection at radical prostatectomy when grade and/or stage increase. 

Published online March 4, 2021. doi:10.1016/j.urology.2021.01.064

4. Cacciamani GE, Maas M, Nassiri N, et al. Impact of pelvic lymph node dissection and its extent on perioperative morbidity in patients undergoing radical prostatectomy for prostate cancer: a comprehensive systematic review and meta-analysis. 

2021;4(2):134-149. doi:10.1016/j.euo.2021.02.001

"Three decades into prostate-specific antigen screening–detected prostate cancer, the prognostic and therapeutic impacts of various types of pelvic lymph node dissection remain unclear," writes Badar M. Mian, MD.

Badar M. Mian, MD

Articles

Postprostatectomy radiation dose and timing affect quality of life

Improved survival is found in mCRPC after PSMA-targeted therapy

QOL after bladder cancer treatment vs other cancers

A tale of 2 lymph node dissections for prostate cancer