A Case of High Risk Localised Prostate Cancer with Nodal Positivity (N+) – Part 2

A Case of High Risk Localised Prostate Cancer with Nodal Positivity (N+) – Part 2

For this second part that I took a few days to prepare, I will first explain about nodal positivity in prostate cancer and then will try to give a fair review for both oncological and surgical management of localised prostate cancer with nodal positivity.

Significances of Nodal Positivity (N+) for Prostate Cancer

Let’s focus on nodal positivity here, N+ or N1, and you can see it’s classified (below) as stage 4 prostate cancer.

AJCC_7th_prostate_3.gif
AJCC staging 7th edition for prostate cancer. TNM staging takes into account T (tumor extension), N (lymph node involvement) and M (distance metastasis). TNM is commonly used together with Gleason score and initial PSA level to improve. Lymph node positivity, N1 or N+, is stage 4 prostate cancer.

It means that nodal positivity carries poorer prognosis.

  • Shorter progression free survival (PFS), prostate cancer specific mortality (PCSM) and overall survival (OS) when compared with other stage I – III prostate cancer.

Are all lymph nodes spread the same?

No.

Some lymph nodes are situated near prostate and is considered regional lymph node (i.e somehow like first station of lymph nodes that prostate cancer cells goes to when out from prostate) and not distance spread/ metastasis.

Regional lymph nodes for prostate cancer are internal and external iliac, obturator and hypogastric lymph nodes (N+).

However, if cancer cells spread to lymph nodes further away such as para-aortic, common iliac, inguinal or femoral lymph nodes, it will be considered as non-regional lymph nodes/ distance metastasis (M+)

Why nodal positivity (N+) is stage 4 even though there is no distance metastasis?

In short, it is classified as stage 4 because the outcomes are similar to patient who has distance metastasis (M+, stage 4).

However, certain subset of N+ patients can still be cured with current more advanced treatments.

Treatments Review: Definitive Radiotherapy, Surgery (Radical Prostatectomy and Pelvic Lymph Node Dissection) and Hormonal Therapy (Androgen Deprivation Therapy).

Stage 4 for N+ prostate cancer doesn’t mean absence of cure.

For prostate cancer with localised regional lymph node positivity (N+), the intention of treatment is curative.

Let’s start with definitive radiotherapy

Definitive/ curative radiotherapy plus androgen deprivation therapy (ADT) is the current standard of care.

The recommended radiotherapy dose to prostate (66Gy – 74Gy) and lymph nodes (45Gy – 50.4Gy) are tolerable to patients. Almost all patients were able to complete planned treatment.

Screenshot 2018-12-03 at 11.07.22 PM.png
Combination treatment; definitive radiotherapy (RT) + androgen deprivation therapy (ADT) resulted in better recurrence free survival (RFS) and overall survival (OS) results than definitive RT alone or ADT alone. Long term data showed that 10 years overall survival is  up to 67%. Even more telling is the 10 years recurrence free survival (80%), meaning that some patients passed away due to other cause than prostate cancer (eg. old age, heart disease, etc.) because only 20% had recurrence prostate cancer in 10 years after definitive RT + ADT.

For gastrointestinal side effects (eg. diarrhoea, rectal bleeding, etc)

  • Acute side effects ranges from 18-47% (mostly are manageable grade 2 toxicities, reversible). Only 1-3% of patients had grade 3 toxicities and none had grade 4 toxicities.
  • For late or prolonged side effects, grade 2 mostly, which affecting 4-10% of patients.

For genitourinary side effects (eg. urinary incontinence, frequent urination, hematuria, etc.)

  • Acute side effects are mostly grade 2 (13-50%, reversible).
  • Late side effects ranges from 3-25% are mostly grade 2 also.

One latest study helped to improve patient selection which might benefit from definitive RT and ADT. (Bryant AK, 2018).

  • Patient with PSA level less than 26 ng/mL, treated with definitive RT and ADT had 50% reduction in risk of prostate cancer specific mortality (PCSM) and 62% reduction in risk of all cause mortality (ACM).
  • In the study conclusion, it was noted that patients with clinically node-positive disease appear to be a heterogeneous cohort, with a subset who may achieve long-term survival with combined RT and ADT.
Screenshot 2018-12-03 at 10.09.30 PM.png
Example of advanced radiotherapy techniques: volumetric modulated arch therapy (VMAT, left) and intensity modulated radiotherapy (IMRT, right).

Surgery – Radical Prostatectomy (RP) and Pelvic Lymph Node Dissection (PLND)

An experienced urologist working in a high volume centre will be the best person to explained about RP + PLND procedure and its pros and cons.

Just for the sake of objectivity and for patients to get an overview, I include this (I’m not a surgeon, please correct me if I’m wrong).

Screenshot 2018-12-03 at 11.07.12 PM.png
Radical prostatectomy role in locally advanced prostate cancer with nodal positivity. There is also long term data up to 10 years here, with 10 years recurrence free survival of 36% and 10 years overall survival up to 51%. Trimodality (RP+PLND, ADT, RT) showed better results but patients may end up with additional side effects and poor tolerability to treatment. The need for adjuvant radiotherapy after surgery is usually due to positive margin or residual tumor. In order to minimise need for additional treatment, careful patient selection for surgery is needed. Every surgeon knows how to operate but it takes an experience and knowledgeable surgeon to know when not to operate.

As a clinical oncologist, I have to be frank here. Malignant tumor or malignant lymph node(s) with size >1cm will need radiotherapy dose of at least 60Gy – 70Gy.

  • In the abdomen, small bowels can tolerate only up to 50.4Gy – 54Gy (smaller volume).
  • Any higher radiotherapy dose required will result in higher adverse acute and dangerous late side effects (intestinal perforation, fistula, strictures, bleeding).
  • Advanced radiotherapy techniques and image guided for proper localisation of tumour may not be useful because small bowels always moves about in the abdominal cavity.
  • These are the limiting the dose factors and dose escalation up to 60Gy and above will not be possible.
  • Downsizing the size of lymph nodes (to < 1cm), either with neoadjuvant ADT or neoadjuvant chemotherapy might be an option before definitive radiotherapy.

The above scenario is where RP + PLND will be beneficial to remove macroscopic tumor, with adjuvant radiotherapy (lower radiotherapy dose) reserved only for any residual tumor (microscopic).

Other benefits of RP + PLND are

  • In patients with complete surgical resection of primary and regional lymph nodes, adjuvant ADT is not required for long term. This will reduce cardiovascular morbidity associated with ADT. Long term ADT increases cardiovascular mortality by 20%. (Saigal, 2007)
  • Reduced risk of second malignancy (bladder and rectal cancer), especially in younger patients with long term survival expected.

What will I choose?

I will choose to have multidisciplinary team (MDT) discussion first to discuss regarding best treatment plan for my patients.

Patients will be in safer hands if specialists are talking with one another, especially in more difficult cases.

#drbhnglatest

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